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GIOVANNI GRANDI
Professore Associato
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
Tutor di tirocinio
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede Policlinico
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Pubblicazioni
2024
- Can immunohistochemistry improve the pathological diagnosis of placenta accreta spectrum (PAS) disorders?
[Articolo su rivista]
Losi, Lorena; Botticelli, Laura; Mancini, Luciano; Negro, Rosa; Hanspeter, Esther; Dematté, Eva; Grandi, Giovanni; Facchinetti, Fabio; Veneziano, Micaela; Malagoli, Claudia; Masini, Meris; Fabbiani, Luca; Rivasi, Francesco
abstract
Purpose: The term of placenta accreta spectrum (PAS) disorder includes all grades of abnormal placentation. It is crucial for pathologist provide standardized diagnostic assessment to evaluate the outcome of management strategies. Moreover, a correct and safe diagnosis is useful in the medico-legal field when it becomes difficult for the gynecologist to demonstrate the suitability and legitimacy of demolitive treatment. The purposes of our study were: (1) to assess histopathologic features according to the recent guidelines; (2) to determine if immunohistochemistry can be useful to identify extravillous trophoblast (EVT) and to measure the depth of infiltration into the myometrium to improve the diagnosis of PAS. Methods: The retrospective study was conducted on 30 cases of gravid hysterectomy with histopathologic diagnosis of PAS. To identify the depth of EVT, immunohistochemical stainings were performed using anti MNF116 (cytokeratins 5, 6, 8, 17, 19), actin-SM, HPL (Human Placental Lactogen), vimentin and GATA3 antibodies. Results: Our cases were graded based on the degree of invasion of the myometrium. Ten were grade 1 (33.3%), 12 grade 2 (40%) and 8 grade 3A (26.7%). EVT invasion was best seen and evident by double immunostainings with actin-SM and cytokeratins, actin-SM and HPL, actin-SM and GATA3. Conclusion: The role of pathologist is decisive to determine the different grades of PAS. A better understanding of the depth of myometrial invasion can be achieved by the use of immunohistochemistry affording an important tool to obtain reproducible grading of PAS. This purpose is crucial in the setting of postoperative quality reviews and particularly in the forensic medicine field.
2024
- Chemoprevention strategies in hereditary breast and ovarian cancer syndromes
[Articolo su rivista]
Barbieri, E.; Venturelli, M.; Mastrodomenico, L.; Piombino, C.; Ponzoni, O.; Zaniboni, S.; Barban, S.; Razzaboni, E.; Grandi, G.; Dominici, M.; Cortesi, L.; Toss, A.
abstract
Hereditary breast and/or ovarian cancer syndromes are inherited disorders in which there is an increased risk of developing breast and/or ovarian cancer in the lifetime, usually at a younger age compared to the general population. Cancer prevention in these syndromes includes prophylactic surgeries, personalized surveillance programs and chemopreventive strategies. Chemoprevention exploits the use of certain drugs or other substances to help lower the risk of developing cancer. In this context, tamoxifen was the first agent considered for breast cancer prevention, followed by raloxifene and the third-generation aromatase inhibitors. On the other hand, the first and most widespread type of chemoprevention for ovarian cancer was combined hormonal contraceptive use. Although several strategies have been studied and showed promising results, only a few of these are currently applied in daily clinical practice. Side effects along with several psychological variables such as cancer perceived risk, worries and related distress, strongly influence women’s decision on chemoprevention. The present review explores and summarizes the available evidence on breast and ovarian cancer chemoprevention approaches.
2024
- Follow-up of early breast cancer in a public health system: A 2024 AIGOM consensus project
[Articolo su rivista]
Gori, S.; De Rose, F.; Ferro, A.; Fabi, A.; Angiolini, C.; Azzarello, G.; Cancian, M.; Cinquini, M.; Arecco, L.; Aristei, C.; Bernardi, D.; Biganzoli, L.; Cariello, A.; Cortesi, L.; Cretella, E.; Criscitiello, C.; De Giorgi, U.; Carmen De Santis, M.; Deledda, G.; Dessena, M.; Donati, S.; Dri, A.; Ferretti, G.; Foglietta, J.; Franceschini, D.; Franco, P.; Schirone, A.; Generali, D.; Gianni, L.; Giordani, S.; Grandi, G.; Cristina Leonardi, M.; Magno, S.; Malorni, L.; Mantoan, C.; Martorana, F.; Meattini, I.; Meduri, B.; Merlini, L.; Miglietta, F.; Modena, A.; Nicolis, F.; Palumbo, I.; Panizza, P.; Angela Rovera, F.; Salvini, P.; Santoro, A.; Taffurelli, M.; Toss, A.; Tralongo, P.; Turazza, M.; Jasonni, Valerio; Verze, M.; Vici, P.; Zamagni, C.; Curigliano, G.; Pappagallo, G.; Zambelli, A.
abstract
Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs. To address these concerns, the Italian Association of Multidisciplinary Oncology Groups (AIGOM) orchestrated a Consensus on early Breast Cancer follow-up utilizing the Estimate-Talk-Estimate methodology. Following the identification of 18 Items and 38 statements by a select Board, 46 out of 54 (85.1%) experts comprising a multidisciplinary and multiprofessional panel expressed their degree of consensus (Expert Panel). The Expert Panel underscores the potential for the multidisciplinary team to tailor follow-up intensity based on the individual risk of recurrence. In selected cases, the general practitioner may be recommended as the clinical lead for breast cancer follow-up, both after completion of adjuvant treatment and at early initiation of endocrine therapy in low-risk patients. Throughout follow-up, and alongside oncologic surveillance, the expert panel advises osteometabolic, cardiologic, and gynecologic surveillance for the early detection and management of early and late treatment toxicities. Moreover, preserving quality of life is emphasized, with provisions for psycho-oncologic support and encouragement to adopt protective lifestyle behaviors.
2024
- Inhibition ratio (I.R.) and transformation index (T.I.): new indexes to compare the effectiveness and clinical behaviour of modern progestin-only pills (POP)
[Articolo su rivista]
Grandi, Giovanni; Barretta, Marta; Feliciello, Lia; Vignali, Michele; La Marca, Antonio
abstract
Progestin-only pills (POPs) have emerged as a crucial contraceptive option for women, particularly those contraindicated to oestrogens. This opinion paper introduces two new indices, the Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.), to evaluate and compare the efficacy and clinical behaviour of modern POPs. The I.R. quantifies the ratio between the progestin dosage in a POP and the minimum dose required to inhibit ovarian function, providing insights into contraceptive efficacy. The T.I., on the other hand, assesses its clinical impact by considering the ratio between the total progestin dose and the dose required to induce endometrial luteinising changes. Both indices thus offer valuable tools for comparing progestins even at significantly different dosages and regimens, providing information on clinical characteristics and drug effects. The newest formulations of POPs (Desogestrel 28 and Drospirenone 24 + 4) have demonstrated higher I.R. and T.I. in comparison to older versions, indicating significant improvements in contraceptive efficacy and clinical impact with better menstrual cycle control. We believe that using these indices will ensure a more informed and personalised choice of progestin not only for contraceptive purposes but also for therapeutic use in gynaecology. The future goal is to develop other progestins with even more advantageous I.R. and T.I., ensuring the best contraceptive efficacy with fewer side effects, even in women at risk (obese, etc.).
2024
- Let's reconsider modern progestin-only pills during isotretinoin and retinoid therapy
[Articolo su rivista]
Manfredini, Marco; Di Castri, Lucio; Grandi, Giovanni
abstract
2024
- Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review
[Articolo su rivista]
Zambelli, A.; Cortesi, L.; Gaudio, M.; Arpino, G.; Bianchini, G.; Caruso, F.; Cinieri, S.; Curigliano, G.; Del Mastro, L.; De Placido, S.; Fabi, A.; Fortunato, L.; Generali, D.; Gennari, A.; Gori, S.; Grandi, G.; Guarneri, V.; Klinger, M.; Livi, L.; Marchiò, C.; Palumbo, I.; Panizza, P.; Pravettoni, G.; Pruneri, G.; Puglisi, F.; Sapino, A.; Tinterri, C.; Turchetti, D.; De Laurentiis, M.
abstract
The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, and the appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk.
2024
- Perception about benefits and risks related to combined hormonal contraceptives use in women with Lynch syndrome
[Articolo su rivista]
Barra, Fabio; Perrone, Umberto; Ferrero, Simone; Bogliolo, Stefano; Ottonello, Silvia; Gustavino, Claudio; Iasci, Angela; Grandi, Giovanni; Pulliero, Alessandra; Centurioni, Maria Grazia; Izzotti, Alberto
abstract
Objective: Lynch syndrome (LS) is a hereditary condition associated with an increased risk of colorectal and endometrial cancer. This study aimed to assess the knowledge, attitudes, and beliefs of women with LS regarding combined hormonal contraceptive (CHC) use compared to a control group of healthy women. Methods: Pre-menopausal women with LS (n = 43) and an age-matched control group of healthy women (n = 128) participated in this prospective, cross-sectional study (NCT05909410). Participants completed an electronic questionnaire evaluating perceptions of CHC use and its impact on various cancers, medical conditions, and symptoms. Statistical analysis compared responses between the two groups, with reported p-values. Results: Women with LS were less likely to use CHCs compared to the control group (p = 0.03) and had a more negative perception of CHCs' impact on colorectal cancer (p = 0.023) and endometrial cancer (p = 0.028). Limited knowledge was observed in both groups regarding the protective effects of CHCs against colorectal and ovarian cancer. Perceptions of CHC use and its impact on symptoms and chronic diseases did not significantly differ between the groups (p > 0.05). CHC use was not associated with greater awareness of the protective effect against colorectal (p = 0.89) and endometrial cancer (p = 0.47), but it was associated with a desire for contraception (OR 21.25; 95% CI 1.16 to 388.21; p = 0.039). Conclusion: This study highlights contrasting perceptions of CHCs and their implications in oncology between women with LS and healthy women. Tailored counselling and support strategies are crucial for empowering women with LS to make informed decisions about their gynaecologic health. KEY MESSAGES center dot This study illuminates divergent perceptions of combined hormonal contraceptives and their oncological implications between women with Lynch syndrome and healthy women. center dot Tailored counseling and supportive strategies are essential for empowering women with Lynch syndrome to make informed decisions regarding their gynecologic health.
2024
- Postpartum contraception: A matter of guidelines
[Articolo su rivista]
Grandi, Giovanni; Del Savio, Maria C; Tassi, Alice; Facchinetti, Fabio
abstract
: The postpartum period is the perfect time to access family planning services. WHO guidelines contraindicate combined hormonal contraceptives postpartum in breastfeeding patients between 6 weeks and 6 months after delivery (Medical Eligibility Criteria category 3). On the contrary, the Faculty of Sexual and Reproductive Healthcare and the Centers for Disease Control and Prevention guidelines do not contraindicate their use in women who breastfeed from 6 weeks to 6 months postpartum. New combined hormonal contraceptives with natural estrogens have never been studied in this setting. Guidelines agree on the prescription of the progestin-only pill postpartum in non-breastfeeding women (category 1). Differences are found in women who breastfeed. In non-breastfeeding women, an implant is considered safe (category 1) by all guidelines, without any distinction in time. Regarding postpartum breastfeeding women, the guidelines for implants give quite different indications but are still permissive. Intrauterine devices are viable options for postpartum contraception but guidelines give different indications about the timing of insertion. Postplacental intrauterine device placement can reduce the subsequent unintended pregnancy rate, particularly in settings at greatest risk of not having recommended postpartum controls. However, it has yet to be understood whether this approach can really have an advantage in high-income countries. Postpartum contraception is not a 'matter of guidelines': it is the best customization for each woman, as early as possible but at the ideal timing.
2024
- Retraction of peer-reviewed articles, a difficult but crucial choice: our experience from The European Journal of Contraception & Reproductive Health Care
[Articolo su rivista]
Roumen, Frans; Grandi, Giovanni; Bitzer, Johannes
abstract
2024
- The oral GnRH antagonists, a new class of drugs in gynecology: from pharmacokinetics to possible clinical applications
[Articolo su rivista]
Barretta, M.; Vignali, M.; La Marca, A.; Grandi, G.
abstract
Introduction: In ovarian steroid-dependent diseases such as uterine fibroids, endometriosis and adenomyosis, oral GnRH antagonists have emerged as new therapeutic alternatives. These oral GnRH antagonists offer key advantages, including oral administration, dose-dependent estrogen suppression and rapid reversibility. Areas covered: This review examines the pharmacological, clinical and therapeutic profiles of the latest non-peptide oral GnRH antagonists, through an analysis of clinical evidence and randomized clinical trials, to provide a comprehensive and up-to-date overview of their clinical applications and potential benefits. Expert opinion: The clinical trials examined demonstrated significant efficacy in reducing heavy menstrual bleeding in women with fibroids and pelvic pain in women with endometriosis, with more than 70% of patients achieving primary endpoints. The use of add-back therapy minimized bone mass density loss, ensuring long-term safety. Adverse events were dose-dependent but generally well tolerated. In our opinion, the strength of oral GnRH antagonists lies in their pharmacological properties. Oral administration increases convenience, allows adjustable dosing and ensures a dose-dependent effect. These drugs provide an immediate antagonistic effect without the flare-up phenomenon. Furthermore, they are expected to act on ectopic endometrial and smooth muscle cell receptors, potentially providing additional anti-proliferative effects. However, further research is needed: long term clinical trials must compare them with existing treatments.
2024
- The use of a pill containing ethinylestradiol-norgestimate improves female sexuality despite the decrease in circulating androgens: a pilot study
[Articolo su rivista]
Guida, Maurizio; Quercitelli, Luciano; De Franciscis, Pasquale; Fiorenza, Mariano; Sgandurra, Alice; La Marca, Antonio; Grandi, Giovanni
abstract
Purpose To evaluate the initial impact of a combined oral contraceptive (COC) containing norgestimate (NGM) on female sexuality and on circulating androgen levels in users. Materials and methods Six months modification in the McCoy Female Sexuality Questionnaire (MFSQ) and testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) serum levels in women starting a monophasic pill containing ethinyl-estradiol (EE) 35 mu g and NGM 0.250 mg. Results The study was completed by 36 subjects. There was a significant increase in MFSQ during treatment (p < 0.0001) (and its domains with the exclusion of vaginal lubrication domain) with concomitant decreases in T (-4.45%, p < 0.0001) and DHEAS (-19.41%, p < 0.0001) serum levels. Conclusions Contraception with EE/NGM was associated with a short term non-deteriorating effect on sexuality despite the evident decrease in androgen levels. Female sexuality during COC use is a complex topic and is not only linked with changes in serum androgen levels.
2024
- Tips and tricks for the management of contraceptive etonogestrel implant in clinical practice: an Expert Opinion
[Articolo su rivista]
Grandi, G.; Feliciello, L.; Sgandurra, A.; Pedrini, V.; Guariglia, G.; Ferrari, V.; Del Duca, N.; La Marca, A.
abstract
The use of long-acting reversible contraceptives (LARCs) is increasing globally due to their higher ability to effectively prevent unintended pregnancies in comparison to short-acting reversible contraceptives (SARCs), especially in adolescence. LARCs include intrauterine devices (copper- or levonorgestrel-releasing) and subcutaneous implants. For LARCs application a dedicated training is needed. Particularly, this Expert Opinion is aiming to open to expert debates on the subcutaneous implant, in particular etonogestrel (ENG)-releasing one, as a cutting-edge form of hormonal contraception. It provides up-to-date guidance about practical advice and technical tips for the ENG implant insertion/removal derived from many years of clinical experience, along with recommendations for the management of unscheduled bleeding during contraception with this method.
2023
- A new progestin-only pill (POP): the impact of drospirenone-only pill 4 mg 24 + 4 on coagulation markers and bleeding patterns
[Articolo su rivista]
Guida, M.; Quercitelli, L.; De Franciscis, P.; Ferrara, C.; Marietta, M.; Iaccheri, M.; Facchinetti, F.; Capasso, F.; Grandi, G.
abstract
Purpose: Progestin-only pills (POPs), compared to combined, are not associated with an increased risk of venous thromboembolism, but are associated with a poor cycle control. The aim of this study was to evaluate the impact of a new POP [4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval] on some coagulation markers (both procoagulant and fibrinolytic) and to describe its impact on bleeding patterns. Materials and methods: This is a prospective trial, based on serum evaluation of following coagulation markers and tests: Factor (F) X, F VIII, F V, INR, aPTT, Protein S and antithrombin III. A ‘bleeding diary’ was used to categorise women as having (1) unscheduled bleeding, (2) scheduled bleeding and (3) amenorrhoea. Thirty patients were followed for six 28-day intake cycles, with a follow-up at the end of the 3rd and 6th cycles. Results: There was a significant decrease of F X (p = 0.03) (-5.7% at cycle 6). No significant changes have been observed for F VII, F V and INR. A significant increase in aPTT (p = 0.01 at 3 cycles), Protein S (p = 0.0006 at 3 cycles) and antithrombin III (p < 0.0001 at 3 cycles) was recorded. This non-deteriorating coagulation impact was associated with a significant and progressive reduction of days of scheduled and unscheduled bleeding in users between cycles 4 and 6 (from 1.3 ± 0.2 days at cycle 4 to 0.8 ± 0.1 days at cycle 6 and from 2.6 ± 0.4 days at cycle 4 to 0.6 ± 0.2 days at cycle 6, respectively, p < 0.0001). Conclusions: DRSP 24 + 4 use was associated with a non-deteriorating effect on coagulation markers and a significant progressive reduction of days of scheduled and unscheduled bleeding.
2023
- Attitudes towards menstruation: what women want? An Italian National Survey
[Articolo su rivista]
Bastianelli, Carlo; Grandi, Giovanni; Farris, Manuela; Brandolino, Gabriella; Paoni Saccone, Giulia; La Barbiera, Ilenia; Benagiano, Giuseppe
abstract
Objective Many women experience negative feelings during menstrual bleeding. Aim of the study was to evaluate the attitudes of Italian women towards menstrual bleeding, their desire to reduce its frequency and knowledge of the existence of methods capable of achieving such an objective. Methods An internet-based anonymous questionnaire has been sent to women willing to fill it in through different social media (Instagram, WhatsApp, Facebook, Twitter). The survey evaluated, objective parameters such as number of pads, use of painkillers, duration of period and pain intensity. Judgement towards period and knowledge about methods to reduce frequency and amount of menstrual flow were analysed. Result 1072 Women aged 18 - 40 years, answered the survey. The level of education of responders was high, with 61.7% having a university degree. 27.5% of respondents viewed positively the occurrence of a menstrual period. Ideal frequency of menstrual cycles was considered 3 months and the perfect duration was considered to be 3 days. Half of the respondents ignored the existence of methods to suppress menstruation or reduce its frequency. 52% of participants stated that they would not use a contraceptive method because they considered it not 'natural'. Conclusions In our sample, in spite of the discomfort reported by half of the women interviewed, menstruation was considered positively by one fourth as because confirm their fertility. The majority of women did consider bleeding every month a healthy, but they preferred a three-monthly frequency. Knowledge of contraceptive methods capable of reducing the frequency of menstrual bleeding was scarce.
2023
- Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations
[Articolo su rivista]
Nebgen, Denise R; Domchek, Susan M; Kotsopoulos, Joanne; de Hullu, Joanne A; Crosbie, Emma J; Paramanandam, Vincent Singh; Brood-van Zanten, Monique M A; Norquist, Barbara M; Guise, Theresa; Rozenberg, Serge; Kurian, Allison W; Pederson, Holly J; Yuksel, Nese; Michaelson-Cohen, Rachel; Bober, Sharon L; da Silva Filho, Agnaldo Lopes; Johansen, Nora; Guidozzi, F; Evans, D Gareth; Menon, Usha; Kingsberg, Sheryl A; Powell, C Bethan; Grandi, Giovanni; Marchetti, Claudia; Jacobson, Michelle; Brennan, Donal J; Hickey, Martha
abstract
Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.
2023
- Combined oral contraceptive with estetrol plus drospirenone: from pharmacokinetics to clinical applications
[Articolo su rivista]
Battipaglia, C.; Feliciello, L.; Genazzani, A. D.; Facchinetti, F.; Grandi, G.
abstract
Introduction: Drospirenone/estetrol (DRSP/E4) is a combined oral contraceptive (COC) recently approved in several countries. It is composed of 15 mg of E4, a natural estrogen produced by human fetal liver throughout pregnancy, and 3 mg of DRSP, the first synthetic progestin used in oral contraception derived from 17-α-spirolactone. E4 and DRSP synergistically prevent pregnancy by inhibiting ovulation. E4 differs from 17-β-estradiol or ethinylestradiol because it represents a native estrogen with selective action in tissues (NEST), therefore it displays both agonist and antagonist estrogenic effects in different tissues. Areas covered: In this paper, we reviewed the scientific literature published in English prior to April 2023 and gathered information on the pharmacodynamics and pharmacokinetics of DRSP, E4 and their combination for contraception. We also proposed possible clinical applications based on the characteristics of the components of this COC. Expert opinion: E4/DRSP-based COC has shown high tolerability, safety and satisfaction and may represent a viable choice in young girls in need of oral contraception and pill users who suffer from high cholesterol, breast tenderness or water retention. Moreover, this new COC shows higher scheduled bleeding rate compared to other pills containing natural estrogens. All the data are reassuring, permitting long-term use.
2023
- Drospirenone 4 mg in a 24 + 4 regimen in women with contraindications to oestrogen use for contraception: bleeding patterns according to previous menstrual characteristics
[Articolo su rivista]
Grandi, Giovanni; Del Savio, Maria Chiara; Melotti, Chiara; Facchinetti, Fabio
abstract
Purpose A new POP consisting of 4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval was developed to improve bleeding predictability during POP use. The aim of this study was to evaluate the effect on bleeding patterns during use of this oral contraceptive (OC) in comparison with previous menstrual cycles before the start of OC use. Methods This is a pilot, prospective trial. A diary was used to collect information about daily bleeding and pelvic pain before and during treatment. During OC use, women were categorised as having (1) unscheduled bleeding or spotting days (UB), (2) scheduled bleeding or spotting days (SB) and (3) absence of bleeding/spotting (AB). SF-36 and FSFI questionnaires were used to quantify health-related quality of life and the quality of sexual life in sexually active participants. Results Eighteen out of twenty-five (72%) women completed the entire follow-up. Women with UB (44.4%) were older at inclusion (p < 0.001) and had higher BMIs (p = 0.02) than those with AB (22.2%) or SB (33.4%). Women recorded a significant reduction of menstrual flow intensity during OC use (p < 0.0001). Those with UB also experienced a significant reduction of menstrual pain intensity (p = 0.006). Women with SB during OC use had a longer baseline cycle than those who reported UB during OC use (p = 0.008). Satisfaction with this OC was very high (8.4 +/- 2.2 points) with no modification in SF-36 and FSFI values. Conclusion A DRSP-only pill is a good OC option for women with contraindications to oestrogen use. Features of the menstrual cycle before the start of OC use may be used to predict associated changes in bleeding patterns.
2023
- Editors’ response
[Articolo su rivista]
Grandi, G.; Roumen, F.; Bitzer, J.
abstract
2023
- Phyto-progestins for the treatment of abnormal uterine bleeding without organic cause in women at high risk for breast cancer and breast cancer survivors: a prospective, pilot study
[Articolo su rivista]
Grandi, Giovanni; Facchinetti, Fabio; Melotti, Chiara; Sgandurra, Alice
abstract
Objectives: Some plants, such as Dioscorea Villosa (DV), Vitex Agnus Castus (VAC) and Turnera diffusa (D) have some 'progesterone-like' properties. We have investigated their simultaneous administration in breast cancer (BC) survivors or carriers of specific genetic mutations that can increase the risk of developing BC suffering from abnormal uterine bleeding without organic cause. Methods: Women with irregular cycles in terms of length (interval between ≤ 24 or ≥ 38 days) without a uterine organic disease (polyps, adenomyosis, fibroids, hyperplasia/malignancy) were included. A daily diary of bleeding, questionnaires about health-related quality of life (Short Form 36) and menstrual psychophysical well-being (PGWB-1) and the Greene Climacteric Scale (GCS) (in women older than 40 years old) questionnaire were used. The presence of some premenstrual syndrome (PMS) symptoms was also evaluated. Results: In the analyzed group of women (n = 15), all experienced a regularization of the menstrual cycles, with a mean duration in the three months of use of 27.1 ± 3.2 days, with a significant reduction of menstrual pain (p = 0.02) and flow (p = 0.02) intensity. Women with PMS (7/15) reported an impovement in depression, headache and abdominal pain scores (p < 0.05). No specific deterioration of different questionnaires evaluated during treatment were observed. General satisfaction with the treatment was 6.8 ± 0.3/10 on a 10 point. Conclusions: A combination of DV, VAC and D could be a promising candidate to treat menstrual irregularities without an organic cause, with a significant reduction of menstrual pain and flow intensity and possible additional benefits in PMS symptoms treatment in women at genetic risk for BC and BC survivors.
2023
- The Association of Four Natural Molecules-EGCG, Folic Acid, Vitamin B12, and HA-To Counteract HPV Cervical Lesions: A Case Report
[Articolo su rivista]
Grandi, Giovanni; Botticelli, Laura; Fraia, Pietro Di; Babalini, Carla; Masini, Meris; Unfer, Vittorio
abstract
Precancerous lesions of the uterine cervix, due to HPV infections, are still today a great medical challenge. This clinical case highlighted the effectiveness of epigallocatechin gallate (EGCG), vitamin B12, folic acid, and hyaluronic acid (HA) in counteracting HPV lesions in a 39-year-old patient with a long history of viral persistence, cervical lesions of various degree, and several unsuccessful surgical approaches. After eight weeks of treatment, both the histological and cytological analyses revealed only a chronic cervicitis without any malignant lesions or cellular dysplasia, thus reducing the urgency of an invasive surgery, a total hysterectomy.
2023
- The drospirenone (DRSP)-only pill: clinical implications in the daily use
[Articolo su rivista]
Kubba, Ali; Gemzell-Danielsson, Kristina; Palacios, Santiago; Wiegratz, Inka; Grandi, Giovanni; Colli, Enrico; Regidor, Pedro Antonio
abstract
Objectives: Progestins used in contraception are either components of combined hormonal contraceptives or are used as a single active ingredient. Progestins are highly effective in long-term contraception and have a very good safety profile with very few contraindications. Methods: An oestrogen-free ovulation inhibitor POP has been authorised in the USA and the EU. It contains 4 mg of drospirenone (DRSP). The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular- phase levels, preventing oestrogen deficiency. Results: Clinical trials have demonstrated high contraceptive effectiveness, a very low risk of cardiovascular risk events and a favourable bleeding pattern. Due to the long half-life of DRSP (30-34 h), the effectiveness is maintained even in case of a forgotten pill on a single occasion. Studies involving deliberate 4 days in one cycle 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. Conclusions: This review article will describe the clinical impact in the daily use of the 4 mg DRSP only pill and the resulting data on the effectiveness and safety of this hormonal contraceptive.
2023
- The impact of epidural analgesia on delivery mode in Robson class 1 women: a retrospective cohort study
[Articolo su rivista]
Ambrosetti, Fedora; Grandi, Giovanni; Petrella, Elisabetta; Sampogna, Veronica; Donno, Lara; Rinaldi, Laura; Ghirardini, Anna Maria; Facchinetti, Fabio
abstract
Background: The use of epidural analgesia represents the gold standard for pain management during labor, but the influence of the use of epidural analgesia on delivery mode is not fully understood. Objective: This study aimed to analyze the impact of epidural analgesia on the delivery mode, namely, cesarean delivery, vaginal delivery, and operative vaginal delivery rates, in Robson class 1 women. Study design: A retrospective cohort study was conducted on all Robson class 1 women who delivered from January 1, 2019, to December 31, 2019, in the University Hospital of Modena. The primary outcome was the delivery mode (cesarean delivery, vaginal delivery, and operative vaginal delivery rates), and the secondary outcomes were maternal, anesthesiologic, and neonatal effects of epidural analgesia (duration of labor, duration of the second stage of labor, Apgar score, and neonatal intensive care unit admission). Results: A total of 744 women were included in the final analysis, of which 198 (26.6%) underwent epidural analgesia on request and 546 (73.4%) did not. In women with and without epidural analgesia, the cesarean delivery rate was 8.1% vs 7%, the vaginal delivery rate was 79.3% vs 81.1%, and the operative vaginal delivery rate was 12.6% vs 11.9%, respectively. A significant increase in both the first stage of labor (66.3±38.5 vs 43.8±38.8 minutes; P<.0001) and total duration of labor (328.0±206.7 vs 201.7±168.3 minutes; P<.0001) was found in women receiving epidural analgesia. No change was recorded in the second stage of labor. A shorter duration of labor was observed (P<.0001) when epidural analgesia was started earlier (dilation: 2-4 cm vs >4 cm). No significant difference in Apgar score and neonatal intensive care unit admission was found. Conclusion: The use of epidural analgesia was not associated with an increased risk of cesarean delivery or operative vaginal delivery in Robson class 1 women. Further investigations are needed to evaluate its impact on the duration of labor, namely the duration of the first stage of labor, and on the possible advantages of starting epidural analgesia at an early stage.
2023
- The role of combined oral contraceptives containing norgestimate for acne vulgaris treatment: a review
[Articolo su rivista]
Grandi, Giovanni; Guariglia, Gloria; Facchinetti, Fabio
abstract
Introduction: Both Food and Drugs Administration and European Medicine Agency (EMA) approve the use of a triphasic combined oral contraceptive (COC) containing ethinyl-oestradiol (EE) and norgestimate (NGM) for acne vulgaris treatment in women requiring an effective contraception. COCs can target sebum production and may also play a role in decreasing follicular hyperkeratinisation.Results: Specific advantages of the use of an anti-androgenic progestin such as NGM in this condition are presented in this review, including the lowest venous thrombosis risk in the COCs scenario, as established by the EMA, associated with a very satisfactory cycle control. The results of aggregate analysis of published data (n = 163 vs. n = 161 treated subjects) demonstrate a significant effect in comparison with the placebo of a greater than 50% reduction, in terms of inflammatory lesions (from 19.0 to 8.2), comedones (from 35.2 to 17.7) and total lesions (from 54.3 to 25.9) count.Conclusions: The choice of a triphasic combination of EE/NGM seems a referenced, highly effective, easy-to-use and safe therapeutic approach for acne vulgaris, alone or in combination with different targeted drugs.
2022
- BRCA mutation carriers’ perception about benefits and risks associated with combined hormonal contraceptives use
[Articolo su rivista]
Grandi, G.; Monari, F.; Boggio Sola, V.; Cortesi, L.; Toss, A.; del Savio, M. C.; Melotti, C.; Centurioni, M. G.; Gustavino, C.; Varesco, L.; Facchinetti, F.; Barra, F.
abstract
To evaluate the actual perceptions about combined hormonal contraceptives (CHCs) use in BRCA mutation carriers in comparison to women from the general population.
2022
- Carboplatin-paclitaxel in triple-negative metastatic breast cancer during pregnancy with neoplastic thrombosis
[Articolo su rivista]
Monari, F.; Grandi, G.; Guidotti, I.; Torcetta, F.; Battista, R.; Coluccio, V.; Piombino, C.; Moscetti, L.; Neri, I.; Toss, A.
abstract
The treatment of breast cancer (BC) diagnosed during pregnancy is a challenging situation for the patient, family and healthcare providers. Here we describe the case of a 35-year-old woman diagnosed with a triple-negative breast cancer relapse during pregnancy. She previously underwent neoadjuvant chemotherapy without any response, subsequent left skin sparing mastectomy plus axillary node dissection and radiation therapy to the chest wall and supraclavicular lymph nodes. Two years later, during her first single pregnancy, the patient presented a subclavian vein thrombosis and a BC relapse to locoregional lymph nodes. At 24 weeks of gestation, a first line treatment with weekly paclitaxel and carboplatin was started. Considering the disease progression after two complete cycles of chemotherapy, the patient had an elective caesarean section at 32+6 weeks. A full-body CT-scan and a PET-scan after the delivery showed a massive neoplastic thrombosis involving the left jugular, brachiocephalic and internal mammary vein, as well the superior vena cava and the right atrium. Few data are available on platinum-based chemotherapy during pregnancy in BC patients. Nevertheless, the choice of therapy was conditioned by the previous absence of response to anthracycline and taxane. In case of BC diagnosis during pregnancy, a multidisciplinary management as in the case described is recommended to increase the chance of survival both for the patients and their babies.
2022
- Confirmation of the safety of combined oral contraceptives containing oestradiol on the risk of venous thromboembolism
[Articolo su rivista]
Grandi, G.; Facchinetti, F.; Bitzer, J.
abstract
2022
- Contraception During Perimenopause: Practical Guidance
[Articolo su rivista]
Grandi, G.; Di Vinci, P.; Sgandurra, A.; Feliciello, L.; Monari, F.; Facchinetti, F.
abstract
Climacteric is by no means in itself a contraindication to safe contraception. On the contrary, there are several conditions related to the perimenopause that could benefit from the use of modern contraceptives, mainly hormonal, with the goals of avoiding unintended pregnancies and giving further possible benefits beyond contraception (menstrual cycle control, a reduction of vasomotor symptoms and menstrual migraines, a protection against bone loss, a positive oncological risk/benefit balance). This narrative review aims to provide practical guidance on their possible use in this particular life stage, both short- and long-acting reversible contraceptives, and to assist clinicians for women transitioning from contraception to their menopausal years, including the possible initiation of postmenopausal hormone therapy. Comprehensive contraceptive counselling is an essential aspect of the overall health and wellbeing of women and should be addressed with each such patient irrespective of age.
2022
- Induction of Labor According to Medical Indications: A Critical Evaluation through a Prospective Study
[Articolo su rivista]
Monari, F.; Pellegrini, R.; Menichini, D.; Spelta, E.; Tarozzi, G.; Grandi, G.; Facchinetti, F.
abstract
Background: The induction of labor (IOL) is a common obstetric intervention, steadily increasing (one out four pregnancies) in the last years. This procedure should be considered only when there is a medical indication, and when the benefits outweigh the maternal and/or fetal risks of waiting for spontaneous onset of labor. Therefore, this study aims to compare the efficacy of the IOL in terms of induction to delivery time, mode of delivery, and neonatal well-being among different evidence-based and non-evidence-based indications. Methods: This prospective study was conducted at the University Hospital of Modena, between January and December 2020. We included singleton pregnant women undergoing IOL, at the term. Intrauterine deaths, small for gestational age fetuses <5th centile as well women with hypertensive disorders were excluded. Women have been subdivided into 3 groups based on the indication to IOL: premature rupture of membranes (PROM), post-date pregnancy (>41 weeks + 3 days), and non-evidence-based indications (NEBI). The primary outcome is the time occurring between IOL and delivery (TIME), analyzing separately by parity. Moreover, mode of delivery and neonatal wellbeing were evaluated. Results: A total of 585 women underwent IOL in the study period. Overall, the median TIME between IOL and delivery was 19 hours, and the mean cesarean section CS rate was 15.5% (91/585). Pregnancies induced for postdate and non-evidencebased indications registered respectively a significantly higher mean time (p < 0.001), compared with women induced for PROM. This occurred both in nulliparous and multiparous women. Moreover, at multivariate analysis, the IOL TIME ≥24 hours was significantly influenced by Bishop score (p = 0.000) and NEBI (p = 0.02) in nulliparous and by gestational age (p = 0.000) and NEBI (p = 0.02) in multiparous. Moreover, CS rate was significantly influenced by Bishop score (p = 0.003) in nulliparous and by gestational age (p = 0.01) in multiparous. Finally, neonatal intensive care unit (NICU) admission resulted significantly influenced only by gestational age (p = 0.002) in multiparous. Conclusions: Our study confirms that IOL in non-evidence-based indications, leads to an increase in induction to delivery time comparing with women induced for PROM, both in nulliparous and multiparous women, thus it should be justified and carefully evaluated. Further randomized controlled trials (RCT) conducted in European/Italian settings are needed to determine the perinatal outcomes of IOL in non-evidence-based indications.
2022
- It is time to talk about replacement of subdermal implants from the same cut, is it always feasible? The slow process of the "armpit approach"
[Articolo su rivista]
Grandi, Giovanni; Feliciello, Lia; Negro, Giulia; Sgandurra, Alice; Facchinetti, Fabio
abstract
2022
- June 24th, 2022: once a right is obtained, it can no longer be lost!
[Articolo su rivista]
Kopp Kallner, Helena; Grandi, Giovanni
abstract
2022
- The use of different doses levonorgestrel-releasing intrauterine system (LNG-IUS): real-world data from a multicenter Italian study
[Articolo su rivista]
Bastianelli, C.; Farris, M.; Rosato, E.; Varliero, F.; Del Savio, M. C.; Facchinetti, F.; Grandi, G.
abstract
Purpose: Current research fails to adequately inform about the differential use of available levonorgestrel-releasing intrauterine systems (LNG-IUSs) in real life. Aim of our study was to compare the characteristics, satisfaction, continuation rates, and adverse effects between users of the high-dose LNG-IUS (52 mg) and of the low dose LNG-IUS (13.5 mg and 19.5 mg). Materials and Methods: A prospective cohort study was performed in two Services for Family Planning in normal menstruating women with the inclusion of all new prescriptions of LNG-IUS for contraception. Women were followed for a mean of 9.1 ± 2.6 months after placement. Results: 109 women (mean age of 39.8 ± 8.7 years old) were included, 69.7% using a high dose LNG-IUS and 30.3% using a low dose LNG-IUS. Women with a low dose LNG-IUS were significantly younger, thinner, more nulliparous, with fewer vaginal deliveries and C-sections, with a lower menstrual flow length and with more previous use of short-acting reversible contraceptives (p < 0.05). LNG-IUS continuation was similar and very high at the last follow-up: 100 vs. 94.7% in the low and high dose LNG-IUS groups, respectively (p = 0.18). Satisfaction with treatment at the end of the study was similar between different LNG-IUS doses (p = 0.85), with 78.9% being satisfied/very satisfied. Bleeding patterns were significantly different between the two LNG-IUS doses (p < 0.0001). Diagnosis of dysfunctional cysts was more frequent in women with high dose compared to low dose LNG-IUS (22.2 vs. 12.1%), albeit not significantly. Conclusions: We have shown a clear differential use of available LNG-IUS in clinical practice, both as baseline characteristics and as different outcomes, primarily for bleeding patterns. However, all these systems were associated with a very high rate of satisfaction and continuation.
2022
- Vitamin D and green tea extracts for the treatment of uterine fibroids in late reproductive life: a pilot, prospective, daily-diary based study
[Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Melotti, C.; Feliciello, L.; Facchinetti, F.
abstract
Objective: The beneficial effects of Vitamin D (VD) and Epigallocatechin gallate (EGCG), a polyphenol of green tea, on the growth of uterine fibroids (UF) were previously described in vitro and in vivo. We have decided to investigate their simultaneous administration in women with UFs in late reproductive life. Methods: >40 years old n = 16 premenopausal women with intramural (IM) or subserosal (SS) UF of ≥3 cm or several UFs of different sizes, even smaller but with a total diameter ≥3 cm but <10 cm, without further concomitant organic causes of abnormal uterine bleeding, treated with EGCG 300 mg, Vitamin B6 10 mg and VD 50 µg/day for 90 days. Women completed a diary on a daily basis to obtain information about bleeding and pelvic pain. Results: We have observed a significant reduction in UF’s mean size both at patient’s (−17.8%, p =.03) and at single UF’s level (−37.3%, p =.015). The effect was more evident in women with predominant IM (p =.016) in comparison to SS UFs. No significant changes were observed for uterine and ovarian volume and endometrial thickness during treatment. We reported a significant decrease in menstrual flow length of 0.9 day (p =.04) with no modification in cycle length, menstrual flow intensity and menstrual pain intensity. The satisfaction with treatment was in general very high, with no adverse effects reported. Conclusion: The concomitant administration of VD and EGCG represents a promising treatment of UF in women of late reproductive life for which hormonal manipulation is not foreseen.
2022
- We don´t have elements to scare women who use oral contraceptives based on nomegestrol or chlormadinone about the risk of meningioma. Let's be careful and honest!
[Articolo su rivista]
Grandi, G.; Marani, G.; Facchinetti, F.; Bahamondes, L.
abstract
2021
- A first trimester prediction model for large for gestational age infants: a preliminary study
[Articolo su rivista]
Monari, F.; Menichini, D.; Spano' Bascio, L.; Grandi, G.; Banchelli, F.; Neri, I.; D'Amico, R.; Facchinetti, F.
abstract
Background: Large for gestational age infants (LGA) have increased risk of adverse short-term perinatal outcomes. This study aims to develop a multivariable prediction model for the risk of giving birth to a LGA baby, by using biochemical, biophysical, anamnestic, and clinical maternal characteristics available at first trimester. Methods: Prospective study that included all singleton pregnancies attending the first trimester aneuploidy screening at the Obstetric Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results: A total of 503 consecutive women were included in the analysis. The final prediction model for LGA, included multiparity (OR = 2.8, 95% CI: 1.6–4.9, p = 0.001), pre-pregnancy BMI (OR = 1.08, 95% CI: 1.03–1.14, p = 0.002) and PAPP-A MoM (OR = 1.43, 95% CI: 1.08–1.90, p = 0.013). The area under the ROC curve was 70.5%, indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 1.378, which corresponds to a 20.1% probability of having a LGA infant. By using such a cut-off, the risk of LGA can be predicted in our sample with sensitivity of 55.2% and specificity of 79.0%. Conclusion: At first trimester, a model including multiparity, pre-pregnancy BMI and PAPP-A satisfactorily predicted the risk of giving birth to a LGA infant. This promising tool, once applied early in pregnancy, would identify women deserving targeted interventions. Trial registration: ClinicalTrials.gov NCT04838431, 09/04/2021.
2021
- Attitudes of women towards products containing hormones (hormonal contraceptives or hormone therapy): what changes from pre to postmenopause?
[Articolo su rivista]
Grandi, Giovanni; Del Savio, Maria Chiara; Boggio Sola, Valentina; Monari, Francesca; Melotti, Chiara; Facchinetti, Fabio
abstract
To evaluate the actual perceptions of hormonal contraceptives (HC) in women of reproductive age in comparison with similar concerns of postmenopausal women in relation to hormone therapy (HT).
2021
- BRCA mutation carriers' perceptions on postmenopausal hormone therapy: An Italian study
[Articolo su rivista]
Grandi, Giovanni; Boggio Sola, Valentina; Cortesi, Laura; Toss, Angela; Giuliani, Giulia Andrea; Del Savio, Maria Chiara; Facchinetti, Fabio
abstract
Objective To evaluate the actual perceptions of postmenopausal hormone therapy (HT) in BRCA mutation carriers (BRCAmc) in comparison with women from the general population.Methods Questionnaire-based study of 83 BRCAmc and a control group of 89 women without a genetic mutation. Perceptions were evaluated by specific questions and Likert scales (-5-+5).Results Present and past users of HT were more frequent in the control group (p = 0.01), with a longer time of use (p = 0.03). The preferred route of administration of HT was 'oral' (54.6%). The most frequently reported adverse effect of HT was venous thrombosis (0.8), while a protective effect on bone health was reported. No noticeable beneficial effects of HT have been recognised for hot flushes (0.2) and vaginal dryness (0.1). The most frequently perceived beneficial and adverse effects of HT were not significantly different between BRCA mutation carriers and controls. The greatest oncological fear was breast cancer (1.0). The protective role of HT on colorectal cancer was not known (0.1). These oncological impacts were mostly overestimated in BRCAmc, however this was not significant. Few BRCAmc would think of taking HT after risk-reducing surgeries.Conclusions Knowledge of the effects of HT on BRCAmc is relatively poor and they are likely to overstate its negative effects and underestimate its health benefits; however, this is not significant in comparison to the general population. More and better information should be given to BRCAmc to allow them to make informed decisions about the use of HT, especially before undergoing risk-reducing surgeries.
2021
- Clinicopathologic Profile of Breast Cancer in Germline ATM and CHEK2 Mutation Carriers
[Articolo su rivista]
Toss, Angela; Tenedini, Elena; Piombino, Claudia; Venturelli, Marta; Marchi, Isabella; Gasparini, Elisa; Barbieri, Elena; Razzaboni, Elisabetta; Domati, Federica; Caggia, Federica; Grandi, Giovanni; Combi, Francesca; Tazzioli, Giovanni; Dominici, Massimo; Tagliafico, Enrico; Cortesi, Laura
abstract
The most common breast cancer (BC) susceptibility genes beyond BRCA1/2 are ATM and CHEK2. For the purpose of exploring the clinicopathologic characteristics of BC developed by ATM or CHEK2 mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen ATM and 17 CHEK2 mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in ATM (26.3%) and CHEK2 mutation carriers (41.2%). While 64.3% of CHEK2 tumors were luminal A-like, 56.2% of ATM tumors were luminal B-like/HER2-negative. Moreover, 21.4% of CHEK2-related invasive tumors showed a lobular histotype. About a quarter of all ATM-related BCs and a third of CHEK2 BCs were in situ carcinomas and more than half of ATM and CHEK2-related BCs were diagnosed at stage I-II. Finally, 63.2% of ATM mutation carriers and 64.7% of CHEK2 mutation carriers presented a positive BC family history. The biological and clinical characteristics of ATM and CHEK2-related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with ATM and CHEK2 mutation carriers at the first diagnosis of BC.
2021
- Contraception and Cardiovascular Diseases
[Capitolo/Saggio]
Del Savio, M. C.; Sammarini, M.; Facchinetti, F.; Grandi, G.
abstract
Women during reproductive years, who need safe contraception, can suffer from many different cardiovascular diseases. This is a comprehensive review about the possible use of different modern contraceptives (intrauterine devices, progestogen-only contraceptives, combined hormonal contraceptives) in women with cardiovascular diseases, such as hypertension, dyslipidaemia, valvular heart disease or arrhythmia or with history of high blood pressure during pregnancy, ischaemic heart disease, cerebrovascular accident or deep-vein thrombosis according to most updated International Guidelines. The main aim of this chapter is to suggest to the clinician when the theoretical or proven risks due to the disease outweigh the advantages of using a method of contraception, in order to avoid unsuitable prescriptions and serious adverse effects.
2021
- Current and future hormonal contraception in Italy: results from an Italian consensus expert meeting
[Articolo su rivista]
Di Carlo, C.; Abbondanza, M.; Agnello, A.; Cavalli, G.; Driul, L.; Petriglia, M.; Tinelli, A.; Tirelli, A.; Tusei, A.; Grandi, G.
abstract
bacKGrOUnd: Hormonal pills are among the most widely contraceptive methods used by women, despite the possible onset of different adverse events. to minimize the risk of thrombosis-related adverse events, different formulations and doses have been investigated. Micronized estradiol (E2)/nomegestrol acetate (NOMAC) 24+4 is the first monophasic combined oral contraceptive pill containing natural e2, the same steroid produced by the granulosa cells of women ovaries. this combination presents an improved effect on hemostasis and metabolism compared to ethinyl-estradiol (ee)based products and may be considered a good option to meet women’s needs in a more physiological way. despite the benefits of E2, its use is still not so common among combined oral contraceptives (COC). MetHOds: seventy-seven italian gynecologists were involved and asked to answer a survey to investigate some aspects related to contraception. the results of the survey were discussed within the same gynecologists and a panel of experts during eight macro-regional meetings. RESULTS: The survey demonstrated that clinicians dedicate 40-60% of their time to contraception and confirmed the importance of the choice of the contraceptive pill, which is mostly prescribed for contraceptive purposes. Moreover, cOc containing E2 is considered as the first choice in oral contraception and meets the features of an ideal pill. CONCLUSIONS: Italian gynecologists reported that E2-based pill presents benefits related to safety, good tolerability, and low adverse events, in particular, related to a reduced thromboembolic risk. research market data highlight that the use of these types of cOc should expand with respect to traditional compounds containing ee.
2021
- Dienogest-based hormonal contraception induced changes in the ultrasound presentation of the uterus and menstrual pain
[Articolo su rivista]
Xholli, A.; Biasioli, A.; Grandi, G.; Cagnacci, A.
abstract
Background: In young women, combined hormonal contraceptives can ameliorate menstrual pain and reduce menstrual loss, but their efficacy in adenomyosis has not been proven. The aim of this study was to investigate whether ultrasound features of adenomyosis are modified by a combined hormonal contraceptive containing dienogest. Methods: Fifty-eight out of 173 premenopausal women consecutively attending our university hospital outpatient service for contraception were enrolled in this observational study. Women with menstrual pain or heavy menstrual bleeding underwent ultrasonography. An expert sonographer diagnosed or excluded adenomyosis and fibroids via morphological uterus sonographic assessment (MUSA). The intensity of menstrual pain was quantified by each patient on a visual analogue scale (VAS). A total of 38 women with and 20 without ultrasound features of adenomyosis received dienogest-based hormonal contraceptive and had a follow-up ultrasound after 6 months of treatment. Results: During treatment, uterine volume decreased by –13.1 ± 22.1% (p = 0.001) in women with adenomyosis features, while it tended to increase in controls. Hypoechoic striation of myometrium present in 95% of cases and myometrial cysts in 5% of cases, respectively, at baseline, had completely disappeared by 6 months. Asymmetry of uterine walls decreased, with the anterior/posterior wall ratio declining from 2.8 ± 0.8. to 1.9 ± 0.7 (p = 0.0001). Heterogeneous myometrial texture, globous uterine morphology, and junctional zone alteration remained unchanged. In women with baseline adenomyosis, VAS score for menstrual pain decreased by –4.0 ± 3.6 (p = 0.0001). During treatment, a VAS score for menstrual pain close to 0 was found in all women without adenomyosis. Days of menstrual flow decreased in women with (p = 0.0001) and without (p = 0.003) adenomyosis. Conclusions: Dienogest-based hormonal contraceptives improve the sonographic features of adenomyosis and improve symptoms. Prospective data are needed to confirm these findings.
2021
- Potentially preventable antepartum stillbirths in a high-resource setting: a prospective audit-based study
[Articolo su rivista]
Po', G.; Salerno, C.; Monari, F.; Grandi, G.; Facchinetti, F.
abstract
Objectives: The primary objective was the identification of sub-standard care in antepartum stillbirths in Emilia-Romagna Region (Italy), hence the number of potentially preventable cases. Secondly, we seek to evaluate any association between inadequate care and either risk factors for stillbirth or causes of death. Study Design: This study was based on prospectively-collected data in an institutional stillbirth audit project, involving all 29 hospital with a maternity unit in Emilia-Romagna Region. For each stillbirth occurred in the area from 2014 to the first semester of 2019 the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death and the quality of care. Two aspects of care quality were evaluated: clinical management and women's access to care. Data were then reviewed by the Regional Audit Group. Results: Elements of inadequate care were identified in 56 out of 524 (10.7 %) fetal deaths. Non-Italian women and pregnancies with fetal growth restriction had double the risk of having received inadequate care during pregnancy, compared to Italian women (aOR 2.0, 95 % CI 1.1–3.6) and a normally developing fetus (aOR 2.0, 95 % CI 1.1–4.1), respectively. Women whose stillbirth was caused by maternal disorders were at higher risk for inadequate care compared to women who had stillbirth explained by other cause (aOR 5.89, 95 %CI 2.2–15.4). Sub-optimal clinical management and barriers to access to care were observed to equal extents. Inappropriate ultrasound monitoring was the most frequent suboptimal care element. Conclusions: About one out of ten stillbirths was potentially preventable. Interventions to reduce stillbirth occurrence in our high-resource setting should focus on appropriate diagnosis and management of maternal disorders and fetal growth restriction, as well as improving access to antenatal care.
2021
- Prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers: what is going on in a region of northern Italy?
[Articolo su rivista]
Grandi, G.; Perrone, A. M.; Perrone, A.; Mandato, V. D.; Comerci, G.; Sammarini, M.; Merisio, C.; Amadori, A.; Stefanetti, M.; Martinello, R.; Facchinetti, F.; De Iaco, P.; Aguzzoli, L.; Arcangeli, V.; Berretta, R.; Cortesi, L.; De Domenico, R.; Nuzzo, M. D.; Friso, S.; Greco, P.; Rosati, F.; Scutiero, G.; Toss, A.
abstract
Background: BRCA1 mutation carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO) between the ages of 35 and 40 or when child bearing is complete, with a possible delay until age 40–45 for BRCA2 mutation carriers. Study Question: Primary outcome was the rate of unsuspected cancer findings during RRSO in a region of northern Italy (Emilia Romagna) and secondary outcomes were details of RRSO: age at surgical intervention, the venue of the procedures in relation to the surgical/pathological quality and the rate/role of concomitant opportunistic hysterectomies. Study Design: Multicentre data collection by invitation to report current RRSO practices. Results: A total of 222 RRSOs (54.5 % BRCA1, 34.7 % BRCA2, 1.8 % BRCA1 and BRCA2 combined, 5.8 % BRCA-VUS and 3.2 % BRCA not better specified) were reported from 9 different centres, half in non-university hospitals and the remainder in university hospitals. Breast cancer survivors (56.3 %) underwent the RRSO at a younger age (47.8 vs 50.6 years, p = 0.02). The mean and median ages at surgical intervention (49.0 and 48.0, respectively) were similar for BRCA1 and BRCA2 mutation carriers, as was the temporal trend in age distribution, and proportions treated in university and non-university hospitals. A diagnosis of ovarian invasive cancer was reported in 3.5 % of subjects, all BRCA1 or BRCA-combined subjects, at a median and mean age of 57 years (range 42–68). Abnormal tubal findings, such as serous tubal intraepithelial lesions (STIL) (100 %), secretory cell outgrowth (SCOUT) (100 %) and STIC (71.4 %), were mainly reported by pathologists in university hospitals. Of the 222 procedures, 15 (6.7 %) included hysterectomies: in none of these cases was a primitive uterine endometrioid or serous cancer found. Conclusions: The results from this multicentre regional study should guide future preventive health policies for RRSO in BRCA mutation carriers.
2021
- Satisfaction with prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers is very high and little dependent on the participants' characteristics at surgery: a prospective study
[Articolo su rivista]
Grandi, Giovanni; Sammarini, Margaret; Cortesi, Laura; Toss, Angela; Botticelli, Laura; Varliero, Federico; Sighinolfi, Giovanna; Barbieri, Elena; Facchinetti, Fabio
abstract
2021
- The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance
[Articolo su rivista]
Grandi, G.; Fiocchi, F.; Cortesi, L.; Toss, A.; Boselli, F.; Sammarini, M.; Sighinolfi, G.; Facchinetti, F.
abstract
OBJECTIVE: Approximately 25% of ovarian cancer (OC) cases are related to an inherited predisposition. Genetic mutations for the oncosuppressor genes BRCA1 and 2 have the best-known linkage to a higher incidence of OC and breast cancer, in approximately 70% to 80% of hereditary OC cases. To provide the first comprehensive clinical description of screen-detected (SD) OCs during a 6-years surveillance of a cohort of young BRCA carriers and carriers who refuse risk-reducing salpingo-oophorectomy. METHODS: A prospective cohort study in a university hospital describing 191 women with BRCA1 and 2 mutations adhering continuously to our surveillance between 2015 and 2020, including a 6-monthly evaluation of cancer antigen 125 (CA 125) with concomitant transvaginal ultrasound (TVUS) performed by a dedicated specialist. Main outcomes were tumor's laterality, CA 125 at diagnosis, TVUS and computed tomography (CT) findings. RESULTS: Risk-reducing salpingo-oophorectomy was performed in 58/191 (30.4%) of mutation carriers during the study period (one OC case identified). Nine SD-OCs and no interval OCs were found in the remaining 133 women. OCs (FIGO stage I or II: 88.9%) occur mainly in BRCA 1 (77.8%), being bilateral in 85.7% BRCA 1 and unilateral in 100% BRCA 2. No lesions involved only the tubes: left ovaries/tubes were more frequently involved. We have described three new possible scenarios regarding imaging: 1) Evident cases (33.3%, TVUS and CT obvious for OC, CA 125 sensitivity: 100%), 2) Possible cases (55.6%, TVUS and CT are in general accordance, documenting new TVUS signs: increased solid pattern of the ovary with peripheral cortical small cysts, hypoechoic circular mass near the ovary, intraparenchymal small hyperechoic foci), and 3) Hidden cases (11.1%, the smallest lesion but the highest stage (IIIA2), with CA 125 44.2 U/mL and concomitant endometrial hyperplasia). CONCLUSIONS: Different diagnostic tools must integrate to ensure early diagnosis of OC in BRCA mutation carriers adhering to a follow-up program.
2021
- The difficult journey to treatment for women suffering from heavy menstrual bleeding: a multi-national survey
[Articolo su rivista]
da Silva Filho, A L; Caetano, C; Lahav, A; Grandi, G; Lamaita, R M
abstract
Purpose Up to 30% of women of reproductive age experience HMB, which has a substantial impact on their quality of life. A clinical care pathway for women with HMB is an unmet need, but its development requires better understanding of the factors that characterise current diagnosis and management of the condition. Materials and methods This observational, survey-based study assessed the burden, personal experiences, and path through clinical management of women with HMB in Canada, the USA, Brazil, France and Russia using a detailed, semi-structured online questionnaire. After excluding those reporting relevant organic pathology, responses to the questionnaire from 200 women per country were analysed. Results Around 75% of women with HMB had actively sought information about heavy periods, mostly through internet research. The mean time from first symptoms until seeking help was 2.9 (Standard deviation, 3.1) years. However, 40% of women had not seen a health care professional about the condition. Furthermore, 54% had never been diagnosed or treated. Only 20% had been diagnosed and received appropriate treatment. Treatment was successful in 69% of those patients currently receiving treatment. Oral contraceptives were the treatment most commonly prescribed for HMB, although the highly effective levonorgestrel-intrauterine system was used by only a small proportion of women. Conclusions This study provides insight into the typical journey of a woman with HMB which may help patients and health care professionals improve the path to diagnosis and treatment, although further research with long-term outcomes is needed.
2021
- The paradigm of norgestimate: a third-generation testosterone-derivative progestin with a peripheral anti-androgenic activity and the lowest risk of venous thromboembolism
[Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Facchinetti, F.
abstract
Introduction: Norgestimate (NGM) is a testosterone derivative with peculiar receptor activities. Areas covered: This is a narrative review of the available data on the pharmacotherapy of NGM in combined hormonal contraceptives (CHCs) in terms of contraceptive efficacy, venous thromboembolism (VTE) risk, safety, tolerability and bleeding patterns. A comprehensive literature review was conducted in August 2020 using PubMed with the keyword ‘norgestimate’. Expert Opinion: NGM shows a mild estrogenic activity associated with anti-mineralocorticoid and anti-androgenic properties, largely responsible for the cardiovascular safety profile. The anti-androgenic property depends on the androgen receptor (AR) nuclear translocation (AR trafficking and its subnuclear distribution), the inhibition of 5α-reductase activity (it possesses higher activity compared to other available progestins), and the increase on sexual hormone binding globulin (SHBG) levels if combined with an estrogenic counterpart. NGM is one of the molecules that best modulates the power of ethinyl-estradiol on the thromboembolic risk, being associated with the lowest VTE risk between different CHCs. NGM has the advantage of retaining peripheral anti-androgenic activity, demonstrated by the impact on lipid and glucose metabolism, and it should be preferred if compared with other similar progestins of the same class of risk which are much more androgenic, such as levonorgestrel.
2021
- The prognostic and predictive role of somatic brca mutations in ovarian cancer: Results from a multicenter cohort study
[Articolo su rivista]
Toss, A.; Piombino, C.; Tenedini, E.; Bologna, A.; Gasparini, E.; Tarantino, V.; Filieri, M. E.; Cottafavi, L.; Giovanardi, F.; Madrigali, S.; Civallero, M.; Marcheselli, L.; Marchi, I.; Domati, F.; Venturelli, M.; Barbieri, E.; Grandi, G.; Tagliafico, E.; Cortesi, L.
abstract
Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.
2020
- Brca detection rate in an italian cohort of luminal early-onset and triple-negative breast cancer patients without family history: When biology overcomes genealogy
[Articolo su rivista]
Toss, A.; Molinaro, E.; Venturelli, M.; Domati, F.; Marcheselli, L.; Piana, S.; Barbieri, E.; Grandi, G.; Piombino, C.; Marchi, I.; Tenedini, E.; Tagliafico, E.; Tazzioli, G.; Cortesi, L.
abstract
NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triplenegative breast cancer (TNBC) patients diagnosed ≤60 years, and 109 luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31–40, 16.1% for those aged 41–50 and 7.9% in 51–60s. A total of 40% of patients with estrogen receptors (ER) 1–9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% BRCA2). Mutation prevalence was 0% between 0–25 years, 9% between 26–30 years and 6% between 31–35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed ≤60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining <10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.
2020
- Breast cancer screening of mutation carriers in the era of COVID-19 pandemic
[Articolo su rivista]
Toss, A.; Lambertini, M.; Punie, K.; Grandi, G.; Cortesi, L.
abstract
2020
- Contemporary prescriptions pattern of different dose levonorgestrel-releasing intrauterine systems in an Italian service for family planning
[Articolo su rivista]
Grandi, G.; De Fata, R.; Varliero, F.; Del Savio, M. C.; Facchinetti, F.
abstract
Objective: Current research informations fail to adequately inform about when levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg is used instead of other lower dose LNG-IUSs (13.5 and 19.5 mg) and other long-acting reversible contraceptives (LARCs) in clinical practice. Methods: A retrospective cohort study was performed in a third-level Service for Family Planning of Modena University hospital about all the first modern contraceptives prescriptions in the whole year 2019 performed by the same group of physicians. All women included underwent a detailed transvaginal ultrasound (TVUS) at prescription and a second evaluation within 3 months when they were still using the prescribed method. Results: To 69/160 (43.1%) women a short-acting reversible contraceptive (SARC), while to 91/160 (56.9%) a LARC was prescribed. Women with a LARC prescription were older than them with a short-acting (SARC) (p <.0001). Women with LNG-IUS 52 mg prescription were significantly the oldest (42.9 ± 5.3), while those with intrauterine copper device and lower dose LNG-IUS were of similar age (36.5 ± 7.3 and 34.9 ± 2.3), significantly lower (p <.005). Women with implant prescription had the same age as SARC, being the youngest (30.7 ± 8.9 and 31.0 ± 9.5) (p <.0001). Women with LNG-IUS 52 mg prescription mg presented with bigger uterine volume (p =.001). In multivariate analyses, the LNG-IUS 52 mg prescription was significantly linked only to age (OR 1.24; 95% CI 1.11–1.37, p <.0001) and presence of adenomyosis (OR 4.56; 95% CI 1.45-14.33, p =.009). Conclusions: The use of LNG-IUS 52 mg instead of other LARCs is preferred for older women, with uteri of increased volume due to adenomyosis, suggesting a possible differential use of available LNG-IUSs in the contemporary clinical practice.
2020
- Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception
[Articolo su rivista]
Fruzzetti, F.; Cagnacci, A.; Primiero, F.; De Leo, V.; Bastianelli, C.; Bruni, V.; Caruso, S.; Di Carlo, C.; Farris, M.; Grandi, G.; Grasso, A.; Guida, M.; Meriggiola, M.; Paoletti, A. M.; Cianci, A.; Nappi, C.; Volpe, A.
abstract
Purpose: The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemia Materials and methods: A concise communication was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented. Results: Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method. Conclusion: At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.
2020
- Drospirenone 4 mg-only pill (DOP) in 24+4 regimen: a new option for oral contraception
[Articolo su rivista]
Chiara Del Savio, M.; De Fata, R.; Facchinetti, F.; Grandi, G.
abstract
Introduction: The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg drospirenone (DRSP) for 24 days plus 4-day hormone-free interval has been developed to address this need. DRSP is a potent progestin analogue of spironolactone, with antiandrogenic and antimineralocorticoid properties. Areas covered: This is a narrative review of the available data on the pharmacotherapy of the new DRSP-only pill. The research includes aspects of pharmacokinetics/pharmacodynamics of the compound: the main focus is on the clinical effects of DRSP-only pill in terms of contraceptive efficacy, haemostatic effect, safety, tolerability and bleeding patterns. Expert Opinion: The DRSP-only pill presents a similar Pearl Index to that of common combined hormonal contraceptives: it is a POP with a better bleeding profile than traditional POPs (higher rates of scheduled bleedings and much lower rates of unscheduled intracyclic bleeding/spotting) which could increase its acceptability and the panorama of possible users. For these reasons, DRSP-only pill represents a real step forward in oral contraception with only progestins, even if the bleeding patterns during its use are still different to oestrogen-containing products (i.e. lower rates of scheduled bleedings and higher rate of amenorrhea).
2020
- Estetrol (E4): the new estrogenic component of combined oral contraceptives
[Articolo su rivista]
Grandi, Giovanni; Chiara Del Savio, Maria; Lopes da Silva-Filho, Agnaldo; Facchinetti, Fabio
abstract
2020
- Postmenopausal hormone therapy in BRCA gene mutation carriers: to whom and which?
[Articolo su rivista]
Grandi, G.; Caroli, M.; Cortesi, L.; Toss, A.; Tazzioli, G.; Facchinetti, F.
abstract
Introduction: Risk-reducing-salpingo-oophorectomy (RRSO) inevitably leads BRCA mutation carriers to premature menopause. Areas covered: To evaluate the existing evidence for use of postmenopausal hormone therapy (HT) in BRCAmc, after RRSO or menopause occurring naturally, for both breast cancer (BC) survivors and those without BC. Expert opinion: All BC survivors are excluded from any HT treatment: in other BRCAmc, before 51 years of age the benefits of HT overcome the risks after RRSO and/or premature ovarian insufficiency (POF). After 51 years of age, it is important to treat only women with important vasomotor symptoms, after the failure of alternative therapies. Estrogens-only therapy plays a key role in hysterectomized women (HW). In the case of an intact uterus (UW), associations with the lowest dose of progestins/natural progesterone derivatives have to be preferred, as progestins has been shown to play an important role in BC transformation, especially in BRCA1mc. No studies have been performed in BRCAmc with regard to ‘progestin-free’ HT, in particular the old tibolone (both in HW and UW) and the new tissue-selective estrogen complex (in UW). However, preliminary data obtained from the general population are reassuring about the use of these ‘progestin-free’ preparations and BC safety.
2020
- Primary fallopian tube carcinoma (PFTC) in a BRIP-1 mutation carrier: the first case report
[Articolo su rivista]
Grandi, G.; Caroli, M.; Alboni, C.; Cortesi, L.; Toss, A.; Barbieri, E.; Botticelli, L.; Facchinetti, F.
abstract
Some hereditary ovarian cancer cases can be associated with a mutation of a gene involved in the DNA double-strand break repair system other than BRCA, such as BRIP1. This mutation is an emerging indication for prophylactic risk-reducing salpingo-oophorectomy (RRSO): however, anomalous tubal pathologic lesions have not yet been reported during RRSO performed for this specific indication (BRIP1), as largely reported for BRCA mutation carriers.An asymptomatic 64-year-old woman with a family history of ovarian and breast cancer agreed to undergo RRSO for a pathogenic variant of the BRIP1 gene (heterozygous NM_032043.2: c.124delT, p. Cys42Valfs) with normal BRCA genes. Histological examination showed the presence of high-grade serous carcinoma of the fimbria of the right tube of a maximum diameter of 0.4 cm (final FIGO stage IIB).The pathogenic mechanism that leads to the development of high-grade serous ovarian/fallopian tube cancer in patients with mutations of BRIP1 should be the same as for patients with mutations of BRCA1 and 2. Our case confirms to consider BRIP1 mutation to be sufficient to justify RRSO at 45–50 years old.
2020
- Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA
[Articolo su rivista]
Piombino, C.; Cortesi, L.; Lambertini, M.; Punie, K.; Grandi, G.; Toss, A.
abstract
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndromes are among the best-known and most extensively studied hereditary cancer syndromes. Nevertheless, many patients who proved negative at BRCA genetic testing bring pathogenic mutations in other suppressor genes and oncogenes associated with hereditary breast and/or ovarian cancers. These genes include TP53 in Li-Fraumeni syndrome, PTEN in Cowden syndrome, mismatch repair (MMR) genes in Lynch syndrome, CDH1 in diffuse gastric cancer syndrome, STK11 in Peutz-Jeghers syndrome, and NF1 in neurofibromatosis type 1 syndrome. To these, several other genes can be added that act jointly with BRCA1 and BRCA2 in the double-strand break repair system, such as PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D. Management of primary and secondary cancer prevention in these hereditary cancer syndromes is crucial. In particular, secondary prevention by screening aims to discover precancerous lesions or cancers at their initial stages because early detection could allow for effective treatment and a full recovery. The present review aims to summarize the available literature and suggest proper screening strategies for hereditary breast and/or ovarian cancer syndromes other than BRCA.
2020
- Surface roughness of different contraceptive vaginal rings: evaluation by scanning electron microscope (SEM)
[Articolo su rivista]
Grandi, G.; Timo, A.; Sammarini, M.; Del Savio, M. C.; Facchinetti, F.
abstract
Objective: The aim of the study was to evaluate whether the compositions of the ethylene vinyl acetate (EVA) membrane of two different contraceptive vaginal rings could influence the surface roughness, which is associated with the possible accumulation of vaginal biomass on the rings during use. Methods: We measured and compared the surface roughness of unused vaginal rings, NuvaRing and Ornibel, using a scanning electron microscope (SEM) and dedicated software that can convert SEM images into 3D models. Average roughness (Ra), average quadratic roughness (Rq) and mean height of the irregularities at 10 points (Rz) were calculated. Results: Different thicknesses of the EVA membranes between the two rings were noted. No significant differences were found between the two rings in the three evaluated values of surface roughness (NuvaRing vs Ornibel, respectively: Ra, 1.53 ± 0.14 vs 1.61 ± 0.14 µm, p = 0.141; Rq, 2.03 ± 0.25 vs 2.07 ± 0.16 µm, p = 0.688; Rz, 11.4 ± 3.1 vs 11.4 ± 2.4 µm, p = 0.987). Conclusion: The different composition of the vaginal rings’ EVA membrane is not associated with different surface roughness. Ornibel is equivalent to NuvaRing in terms of surface roughness, despite the different composition of the membrane polymers.
2020
- The gendered impact of coronavirus disease (COVID-19): do estrogens play a role?
[Articolo su rivista]
Grandi, G.; Facchinetti, F.; Bitzer, J.
abstract
Objective: Although sex-disaggregated data for COVID-19 show equal numbers of cases between men and women, there seem to be sex differences in mortality rate and vulnerability to the disease: more men than women are dying. Methods: We have explored the potential role of estrogens in this COVID-19 gendered impact. Results: Estrogens stimulate the humoral response to viral infections, while testosterone and progesterone give an immune suppression of both innate and cell-mediated immune responses. We hypothesise that estrogens, in particular estradiol but also synthetic estrogen such as ethinylestradiol, could protect women from the most serious complications of COVID-19. The use of medications that keep hormonal levels high and stable, such as combined hormonal contraceptive, could therefore play a protective role. These potential benefits overtake the thrombotic risk in healthy women. As stated by the World Health Organization, all modern methods of contraception were safe to use during the COVID-19 pandemic.
2020
- The generally low sensitivity of CA125 for FIGO stage I ovarian cancer diagnosis increases for endometrioid histotype
[Articolo su rivista]
Grandi, G.; Perrone, A. M.; Toss, A.; Vitagliano, A.; Friso, S.; Facchinetti, F.; Cortesi, L.; Cascinu, S.; Deiaco, P.
abstract
BACKGROUND: The serum marker CA125 is still the most widely used biomarker for ovarian cancer (OC) diagnosis in gynecological and oncological setting, but its predictive role in early-stage OCis still debated. The aim of this study was to explore the value of CA125 in distinguishing between early-stage OCand borderline ovarian tumor (BOT) and to evaluate the accuracy of CA125 in the detection of early stage OC. METHODS: Aretrospective cohort study was performed at the University Hospital of Bologna (Italy) on 1296 consecutive women suffering from OCor BOT (diagnosed at histology) between 1988-2017. Patients for whom CA125 level was determined preoperatively were included. The positive cut-off level used was >35 U/mL. RESULTS: Of 910 patients, 192 (21.1%) were diagnosed with BOT and 718 (78.9%) with OC. The sensitivity of CA125 for stage IOCwas 54.4 (95% CI: 45.3-63.3) (51.5 for IA, 54.6 for IB, 58.3 for IC), but it increased to 78.0 (95% CI: 63.7-88.0) for stage II. Interestingly, in stage I OC, CA 125 presented a significantly higher sensitivity for the endometrioid histotype [72.4 (95% CI: 52.5-86.5) vs. 49.0 (95% CI: 38.6-59.4), P=0.026]. The positive likelihood ratio of CA125 for early-stage OCcompared to BOT was 1.29 (95% CI: 1.06-1.58). CONCLUSIONS: Despite its limited sensitivity for early-stage OCs, CA125 still represents a useful serum marker to early differentiate between OCs and BOTs. Its sensitivity for stage IOCincreases in endometrioid histotype.
2020
- The impact of COVID-19 lockdown on admission to gynecological emergency departments: Results from a multicenter Italian study
[Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Caroli, M.; Capobianco, G.; Dessole, F.; Tupponi, G.; Petrillo, M.; Succu, C.; Paoletti, A. M.; Facchinetti, F.
abstract
Objective: To evaluate the impact of the COVID-19 lockdown on admissions to gynecological emergency departments (ED) of three Italian university hospitals with different rates of COVID-19 incidence. Methods: A retrospective study was conducted in the gynecological EDs of Modena (Emilia-Romagna), Sassari and Cagliari (Sardinia) regarding all admissions to gynecological EDs during November 1 to 30, 2019, and March 11 to April 9, 2020 (lockdown period). Results: A total of 691 women (mean age 38.3 ± 14.3 years) who were admitted to the gynecological EDs were included. The relative decrease in women evaluated from March 11 to April 9, 2020, was −56.6% (95% confidence interval [CI] 52.2–61.1). Time spent in the ED was also significantly shorter during this period (P=0.02) in comparison to November 1 to 30, 2019. The most evident decrease was observed for pelvic pain (−68.9% [95% CI 60.3–76.7]; −91 cases). The management of women suggests a more effective use of the ED, with higher rates of hospitalization (P=0.001) and recourse to emergent surgeries (P=0.005) and lower rates of discharge to home (P=0.03). Conclusion: The COVID-19 lockdown greatly reduced the rate of admission to gynecological EDs, but the real emergencies were filtered from the more deferrable ones.
2020
- The reduction of CA 125 serum levels in BRCA 1/2 mutation carriers after risk-reducing salpingo-oophorectomy is only partially associated with surgery: A prospective cohort, other biomarker controlled, study
[Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Sammarini, M.; Cortesi, L.; Toss, A.; Piombino, C.; Facchinetti, F.
abstract
Objectives A significant reduction in CA 125 postoperative serum levels was observed after risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers. In contrast to previous studies, where control groups were absent, we conducted a prospective study including also a screening only group (RSSO refusal) and a group having previously undergone RRSO. Methods Consecutive BRCA1 and BRCA2 mutation carriers, not hysterectomised, >35 years old and with completed childbearing, were recruited. Some women had previously undergone RRSO (previous RRSO group). The others, who had either chosen RRSO (actual RRSO group) or screening only (screening only group), were enrolled (patient-preference trial). A prospective evaluation (basal and 6-month) of CA 125 and CEA (control biomarker) was performed. Results The study consisted of 116 women, 44.8% BRCA1 and 55.2% BRCA2 mutation carriers (n = 25 in the previous RRSO group, n = 29 in the actual RRSO group, n = 62 in the screening only group). For all subjects, we observed a 6-month decrease in CA 125 (-7.8%, P = 0.003), which was significantly linked only to endometriosis history (odds ratio 1.4; 95% confidence interval 1.1-1.8; P = 0.002). Between different groups, we recorded a non-significantly different decrease in CA 125. CEA showed a 6 months significant increase (+15.4%, P < 0.0001), which was similar between groups. Conclusion The decrease in CA 125 in BRCA mutation carriers after RRSO was only partially associated with surgery, depending also on a physiological decline: This is extremely important in their longitudinal monitoring for the prevention of ovarian cancer.
2019
- A comprehensive review of hormonal and biological therapies for endometriosis: latest developments
[Articolo su rivista]
Barra, F.; Grandi, G.; Tantari, M.; Scala, C.; Facchinetti, F.; Ferrero, S.
abstract
Introduction: Endometriosis is a chronic benign estrogen-dependent disease characterized by the presence of endometriotic glands and stroma outside the uterine cavity. Although combined hormonal contraceptives and progestins, currently available first-line treatments for endometriosis, are efficacious and well tolerated for treating disease-related pain, some women experience partial or no improvement of pain or its recurrence is frequent after discontinuation of the therapies. For these reasons, new drugs are under investigation for the treatment of endometriosis. Areas covered: This review aims to give to the reader a complete and updated overview of hormonal and biological therapies for the treatment of endometriosis, underlining the latest developments in this field of research. Expert opinion: Among the new drugs investigated, late clinical trials on gonadotropin-releasing hormone (GnRH) antagonists and aromatase inhibitors (AIs) have demonstrated the most promising results. For this reason, elagolix, a new GnRH-antagonist, recently received the approval by the Food and Drug Administration (FDA) for treating pain associated to endometriosis. Other drugs with innovative targets have been identified, but the majority of these compounds have only been evaluated in pre-clinical studies or early clinical trials. Thus, a further extensive clinical research is necessary to better elucidate their pharmacologic characteristics, their efficacy, and safety for the treatment of this benign chronic disease.
2019
- A regional audit system for stillbirth: A way to better understand the phenomenon
[Articolo su rivista]
Po, G.; Monari, F.; Zanni, F.; Grandi, G.; Lupi, C.; Facchinetti, F.; Mancini, L.; Lugli, L.; Lanzoni, C.; Sgarbi, L.; Chiossi, C.; Ricchieri, F.; Roberta, C.; Contiero, R.; Garani, G.; Pedriali, M.; Rossi, S.; Fini, S.; Di Bartolo, M.; Radi, D.; Vancini, A.; Donati, A.; Guadalupi, E.; Righetti, F.; Salerno, A.; Cocchi, G.; Morandi, R.; Gabrielli, L.; Graziano, C.; Seri, M.; Caprara, G.; Mario, S. N. C.; Fantuz, F.; Ferlini, F.; Righi, E.; Silvestrini, D.; Foschi, F.; Fieni, S.; Frusca, T.; Ferretti, A.; Galli, L.; Magnani, C.; Silini, E.; Balduzzi, L.; Bellini, M.; Rodolfi, A. M.; Sgarabotto, M. P.; Fragni, G.; Comitini, G.; Bonasoni, M. P.; Fioroni, L.; Rozzi, C.; Tuzio, A.; Vito, I.; Mammoliti, P.; De Ambrosi, E.; Ricci, M.; Bandini, A.; Belosi, C.; Muratori, C.; Zago, S.; Turci, A.; Vitarelli, M.
abstract
Background: Implementation of high-quality national audits for perinatal mortality are needed to improve the registration of all perinatal deaths and the identification of the causes of death. This study aims to evaluate the implementation of a Regional Audit System for Stillbirth in Emilia-Romagna Region, Italy. Methods: For each stillbirth (≥ 22 weeks of gestation, ≥ 500 g) occurred between January 1, 2014 to December 1, 2016 (n = 332), the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death (ReCoDe classification) and the quality of care. Data were reviewed by the Regional Audit Group. Stillbirth rates, causes of death and the quality of care were established for each case. Results: Total stillbirth rate was 3.09 per 1000 births (332/107,528). Late stillbirth rate was 2.3 per 1000 (251/107,087). Sixteen stillbirths were not registered by the Regional Birth Register. The most prevalent cause of death was placental disorder (33.3%), followed by fetal (17.6%), cord (14.2%) and maternal disorders (7.6%). Unexplained cases were 14%. Compared to local audits, the regional group attributed different causes of death in 17% of cases. At multivariate analysis, infections were associated with early stillbirths (OR 3.38, CI95% 1.62-7.03) and intrapartum cases (OR 6.64, CI95% 2.61-17.02). Placental disorders were related to growth restriction (OR 1.89, CI95% 1.06-3.36) and were more frequent before term (OR 1.86, CI95% 1.11-3.15). Stillbirths judged possibly/probably preventable with a different management (10.9%) occurred more frequently in non-Italian women and were mainly related to maternal disorders (OR 6.64, CI95% 2.61-17.02). Conclusions: Regional Audit System for Stillbirth improves the registration of stillbirth and allows to define the causes of death. Moreover, sub-optimal care was recognized, allowing to identify populations which could benefit from preventive measures.
2019
- Combined hormonal contraceptives in BRCA gene mutation carriers: why not?
[Articolo su rivista]
Grandi, Giovanni; Sammarini, Margaret; del savio, maria chiara; Toss, Angela; Facchinetti, Fabio
abstract
not available
2019
- Easy tools to screen Italian women suffering from migraine with and without aura in early reproductive age
[Articolo su rivista]
Grandi, G.; Imbrogno, M. G.; Cainazzo, M. M.; Pini, L. A.; Baraldi, C.; Guerzoni, S.; Nappi, R. E.; Facchinetti, F.
abstract
Objective: Early diagnosis of migraine with (MA)/without aura (MO) is vitally important to prevent adverse events during combined hormonal contraceptive (CHC) use and to provide personalized surveillance programs during pregnancy. The aim of this study is to provide clinicians with simple and fast tools to diagnose MO and MA in daily clinical practice. Study design: This study was based on a questionnaire to women of early reproductive age (18–35 years old) then randomized to undergo a neurological consultation. The ID-migraine questionnaire (PIN) and visual aura rating scale (VARS) were used. Results: A total of 240 subjects were included in the study, with a total prevalence of MO diagnosed by PIN of 67.0% of subjects with headache, 49.2% of the total study population, and of MA by VARS of 12.5% subjects with headache, 9.2% of the total study population. Eighty-seven neurological examinations were randomly performed: PIN showed a sensitivity of 85.7% (95% CI 75.3%–92.9%) and a specificity of 52.9% (95% CI 27.8%–77.0%), while VARS displayed a sensitivity of 100.0% (95% CI 69.2%–100.0%) and a specificity of 45.5% (95% CI 16.8%–76.6%). Conclusion: High sensitivity, in particular for the presence of MA, associated with low specificity suggest that PIN and VARS questionnaires can be effective tools to identify those young patients who require specific neurological examinations in view of the prescription of a CHC or pregnancy planning.
2019
- Estradiol in non-oral hormonal contraception: a “long and winding road”
[Articolo su rivista]
Grandi, G.; Barra, F.; Ferrero, S.; Facchinetti, F.
abstract
2019
- Future directions in endometriosis treatment: discovery and development of novel inhibitors of estrogen biosynthesis
[Articolo su rivista]
Barra, F.; Romano, A.; Grandi, G.; Facchinetti, F.; Ferrero, S.
abstract
2019
- Hereditary ovarian cancers: State of the art
[Articolo su rivista]
Toss, A.; Molinaro, E.; Sammarini, M.; Del Savio, M. C.; Cortesi, L.; Facchinetti, F.; Grandi, G.
abstract
The identification of a mutation in ovarian cancer (OC) predisposition genes plays a crucial role in the management of cancer prevention, diagnosis, and treatment. In healthy carriers, the detection of a specific mutation might justify more intensive and personalised surveillance programmes, chemopreventive measures, and prophylactic surgeries. Moreover, the identification of a mutation in affected OC patients might provide fundamental knowledge of the tumour pathogenesis, thus guiding treatment choices. This is a comprehensive review of the molecular pathways involved in the pathogenesis of hereditary ovarian cancers, the clinical-pathological features of these tumours, and the potential implications for their prevention and clinical management.
2019
- Hormonal contraception in women with endometriosis: a systematic review
[Articolo su rivista]
Grandi, G.; Barra, F.; Ferrero, S.; Sileo, F. G.; Bertucci, E.; Napolitano, A.; Facchinetti, F.
abstract
Objective: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence. Methods: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment. Results: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence. Conclusions: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.
2019
- Increasing BMI is associated with both endometrioid and serous histotypes among endometrial rather than ovarian cancers: a case-to-case study
[Articolo su rivista]
Grandi, G.; Perrone, A. M.; Chiossi, G.; Friso, S.; Toss, A.; Sammarini, Margaret; Facchinetti, F.; Botticelli, L.; Palma, F.; De Iaco, P.
abstract
Aim: Although obesity has been associated with endometrioid (type I) and, to a lesser extent, with serous (type II) endometrial cancer (EC), the association with the same histotypes of ovarian cancer (OC) remains unclear. Therefore, we intended to compare the role of BMI in carcinogenesis of endometrioid and the serous malignancies, at both ovarian and endometrial level. Methods: A retrospective case-to-case study was performed in the University Hospital of Bologna (Italy), through the review of primary EC matched with the corresponding OC cases in the same period (1988–2017). Results: We included 1052 women diagnosed with EC (n = 897 endometrioid, n = 52 serous) and 955 women affected by OC (n = 132 endometrioid, n = 627 serous). EC patients had higher median BMI than women diagnosed with OC (27.3 [23.4–31.9] vs 24.9 [21.7–27.5], p < 0.01). After controlling for confounding, 1 unit increase in BMI was associated with a 5% higher odds of endometrial as opposed to ovarian cancer (OR for ovarian as opposed to endometrial cancer 0.95; 95% CI 0.91–0.98, p = 0.004). Conclusions: Increasing BMI is associated with endometrial rather than ovarian cancer, among both serous and endometrioid histotypes.
2019
- Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials
[Articolo su rivista]
Facchinetti, F.; Orru, B.; Grandi, G.; Unfer, V.
abstract
Metformin (MET), the most commonly used insulin sensitizer, is the reference off-label drug for the treatment of polycystic ovary syndrome (PCOS), worldwide. However, its use may be limited mainly by gastrointestinal adverse effects. Myo-inositol (MI), a well-recognized food supplement, also represents an evidence-based treatment for PCOS women, popular in many countries. Our aim is to provide a systematic review of the literature and a meta-analysis which compares these two treatments, for their short-term efficacy and safety in PCOS patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). RCTs were identified from 1994 through 2017 using MEDLINE, Cochrane Library, PubMed, and ResearchGate. Included studies were limited to those one directly comparing MET to MI on several hormones changes. Standardized mean difference (SMD) or risk ratios (RRs) with 95% CIs were calculated. Changes in fasting insulin was the main outcome of measure. Six trials with a total of 355 patients were included. At the end of treatment, no difference between MET and MI was found on fasting insulin (SMD=0.08 µU/ml, 95% CI: −0.31–0.46, p=.697), HOMA index (SMD =0.17, 95% CI: −0.53–0.88, p=.635), testosterone (SMD= −0.01, 95% CI: −0.24–0.21, p=.922), SHBG levels (SMD= −0.50 nmol/l, 95% CI: −1.39–0.38, p=.263) and body mass index (BMI) (SMD= −0.22, 95% CI: −0.60–0.16, p=.265). There was strong evidence of an increased risk of adverse events among women receiving MET compared to those receiving MI (RR =5.17, 95% CI: 2.91–9.17, p<.001). No differences were found in the effect of MET and MI on short-term hormone changes. The better tolerability of MI makes it more acceptable for the recovery of androgenic and metabolic profile in PCOS women.
2018
- Combined Hormonal Contraceptive Use and Risk of Breast Cancer in a Population of Women With a Family History
[Articolo su rivista]
Grandi, Giovanni; Toss, Angela; Cagnacci, Angelo; Marcheselli, Luigi; Pavesi, Silvia; Facchinetti, Fabio; Cascinu, Stefano; Cortesi, Laura
abstract
We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic.
2018
- Levonorgestrel-releasing intra-uterine systems as female contraceptives
[Articolo su rivista]
Grandi, Giovanni; Farulla, Antonino; Sileo, Filomena Giulia; Facchinetti, Fabio
abstract
The availability and use of long-acting reversible contraceptives (LARCs), such as levonorgestrel intrauterine systems (LNG-IUSs), have increased in recent times. Areas covered: The authors provide a narrative review of the LNG-IUSs currently available worldwide as female contraceptives (LNG-IUS 13.5, 19.5 and 52 mg). Specific features of the devices and their parameters of efficacy and tolerability were considered as outcomes. Expert opinion: The one-handed 3.8-mm-diameter inserter of LNG-IUS 13.5 mg and 19.5 mg may be particularly suitable in nulliparous women. While LNG-IUSs 13.5, 19.5 mg and LNG 52 mg should be used by women simply looking for an effective contraceptive method for up to 3, 4 or 5 years, LNG-IUS 52 mg has also been approved for the treatment of heavy menstrual bleeding and endometrial protection during hormone replacement therapy. LNG-IUS 52 mg is ideal for women who are experiencing a certain hyperestrogenic hormonal environment, with heavy menstrual bleeding due to hormonal imbalances, adenomyosis or fibroids, in the case of symptomatic endometriosis or for endometrial protection during hormone estrogenic replacement therapy in non-hysterectomized women.
2017
- A comparison of two implants with conical vs internal hex connections: 1-year post-loading results from a multicentre, randomised controlled trial
[Articolo su rivista]
Cannata, M.; Grandi, T.; Samarani, R.; Svezia, L.; Grandi, G.
abstract
Purpose: To compare the clinical and radiological outcomes of identical implants with conical or internal hex connections. Methods: A total of 90 patients with partial edentulism requiring one implant-supported prosthesis were randomly allocated in two equal groups (n = 45) to receive either implants with a conical connection or implants of the same type, but with an internal hex connection at three centres. Patients were followed for 1 year after loading. Outcome measures were implant failures, any complication and marginal bone level changes. Results: One patient (2.2%) belonging to the internal hex group dropped out. One implant (2.2%) failed in the conical group. There were no statistically significant differences in implant failures between the two groups (2.2% vs. 0%, difference 2.2; 95% CI: -1.3; 5.7; P = 0.315). Two complications occurred in the conical group and two in the internal hex group (P = 1.000, difference 0.00, 95% CI: -3.1; 3.1). The 12-month peri-implant bone resorption was similar in both groups: 0.56 ± 0.53 mm (95% CI 0.03; 1.09) in the conical group and 0.60 ± 0.62 mm (95% CI 0.02; 1.22) in the internal hex group (difference = 0.04 ± 0.55, 95% CI: -0.51; 0.59, P = 0.745). Conclusions: Within the limitation of this study, preliminary short-term data (1 year post-loading) did not show any statistical differences between the two internal connection types, therefore clinicians could choose whichever connection they prefer.
2017
- Association between urinary incontinence and climacteric symptoms in postmenopausal women
[Articolo su rivista]
Cagnacci, Angelo; Palma, Federica; Carbone, Maria Maddalena; Grandi, Giovanni; Xholli, Anjeza
abstract
OBJECTIVE:: The aim of the study was to evaluate whether climacteric symptoms are related to urinary incontinence (UI) in postmenopausal women. METHODS:: A cross-sectional investigation was performed on 1,502 postmenopausal women attending the outpatient service for menopause at a University Hospital. Data regarding climacteric symptoms, evaluated by the Greene Climacteric Scale, objective pelvic floor defects, and UI of any type, were retrieved from an electronic database. Additional information retrieved were age, anthropometric measures, personal and reproductive history, use of medication or drugs, smoking, state of anxiety (State-Trait Anxiety Inventory scale score), and depression (Zungʼs scale score). RESULTS:: The score of the Greene Climacteric Scale was higher (P?=?0.0001) in women with (n?=?534) than without (n?=?902) UI (32.3?±?13.1 vs 26.5?±?12.5; P?<?0.0011). The same was true when considering stress (n?=?370) (31.4?±?13.4; P?=??0.0007), urge (n?=?84) (34.5?±?13.5; P?=??0.005), or mixed (n?=?89) (34.3?±?11.4; P?=??0.006) UI. In multiple logistic regression models, the Greene climacteric score was independently related to UI (odds ratio [OR] 1.05; 95% CI, 1.03-1.07), along with the presence of a bladder prolapse (OR 3.72; 95% CI, 2.59-5.34), age at menopause (OR 1.05; 95% CI, 1.01-1.09), and previous hysterectomy (OR 1.80; 95% CI, 1.08-3.01). Women in the fourth quartile of the Greene Climacteric Scale score had an OR of UI of 2.09 (95% CI, 1.5-2.9). CONCLUSIONS:: In postmenopausal women, higher symptom burden, as captured by the Greene Climacteric Scale, relates to UI. Underlying mechanisms were not assessed, and deserve further investigation.
2017
- ESC expert statement on the effects on mood of the natural cycle and progestin-only contraceptives
[Articolo su rivista]
Merki-Feld, G. S.; Apter, D.; Bartfai, G.; Grandi, G.; Haldre, K.; Lech, M.; Lertxundi, R.; Lete, I.; Lobo Abascal, P.; Raine, S.; Roumen, F.; Serfaty, D.; Shulman, L. P.; Skouby, S.; Bitzer, J.
abstract
Hormonal fluctuations during the natural cycle, as well as progestins used for hormonal contraception, can exert effects on mood especially in vulnerable women. Negative effects of levonorgestrel-releasing intrauterine contraception on mood are rare.
2017
- Estradiol in hormonal contraception: real evolution or just same old wine in a new bottle?
[Articolo su rivista]
Grandi, Giovanni; Facchinetti, Fabio; Bitzer, Johannes
abstract
The first combined hormonal contraceptive (CHC) was introduced in 1960 by Gregory Pincus [1 Pincus G, Garcia CR, Rock J, et al. Effectiveness of an oral contraceptive. Science. 1959;30:81–83.
[Crossref], [Web of Science ®], [Google Scholar]
] composed by an oral estrogenic and progestin component mestranol and norethinodrel, respectively.
Over the last 55 years, the traditional pill has constantly evolved. After the early attempts with mestranol, the use of ethinyl-estradiol (EE) became predominant for decades until a few years ago [2 Grandi G, Cagnacci A, Volpe A. Pharmacokinetic evaluation of desogestrel as a female contraceptive. Expert Opin Drug Metab Toxicol. 2014;10:1–10.
[Taylor & Francis Online], [Web of Science ®], [Google Scholar]
]. The EE doses were gradually decreased up to 15 µg. At the same time, numerous different generations of progressively weaker androgenic and even anti-androgenic progestins were tested in order to have products that better fits individual needs. The replacement of EE with estradiol (E2), the estrogen naturally secreted by the granulosa cells of the human ovary, was difficult because of the failure to achieve a satisfactory bleeding control [3 Fruzzetti F, Bitzer J. Review of clinical experience with estradiol in combined oral contraceptives. Contraception. 2010;81:8–15.
[Crossref], [PubMed], [Web of Science ®], [Google Scholar]
].
2017
- Evaluation of Transvaginal Ultrasound plus CA-125 Measurement and Prophylactic Salpingo-Oophorectomy in Women at Different Risk Levels of Ovarian Cancer: The Modena Study Group Cohort Study
[Articolo su rivista]
Cortesi, Laura; De Matteis, Elisabetta; Toss, Angela; Marchi, Isabella; Medici, Veronica; Contu, Giannina; Xholli, Anjeza; Grandi, Giovanni; Cagnacci, Angelo; Federico, Massimo
abstract
Objective: To evaluate the effectiveness of transvaginal ultrasound (TVU) and serum CA-125 measurement in women at different risk of developing ovarian cancer/fallopian tube cancer (OC/FTC) and the incidence of primary peritoneal cancer (PPC) after risk-reducing salpingo-oophorectomy (RRSO). Methods: Between 2002 and 2014, 661 women at different risk of OC/FTC/PPC due to a family history or BRCA1/2 gene mutation were offered TVU and CA-125 measurement or RRSO as prevention strategies. The detection rate of OC/FTC/PPC was evaluated, and the sensitivity and specificity for CA-125 measurement and TVU were calculated. Survival and event analysis was performed for diagnosed patients. Results: After a median follow-up of 112 months, 12 OC/FTC/PPC cases were detected (2.6/1,000 persons/year). The screening sensitivity was 70%, with 73% for BRCA carriers. Six (50%) of 12 cancers were stage I or II. Among 41 women who underwent RRSO, 2 BRCA1 carriers developed a PPC (4.9%). At 61-month follow-up, overall and event-free survival were 75 and 64%, respectively. Conclusions: The cancer detection rate in women with BRCA mutation or a strong family history supports the effectiveness of our surveillance program for early diagnosis. Screening for women at lower risk of OC/FTC is not recommended. A residual risk of PPC after RRSO remains for BRCA1 carriers.
2017
- Laparoscopic management of ectopic pregnancies: a comparison between interstitial and “more distal” tubal pregnancies
[Articolo su rivista]
Nirgianakis, K.; Papadia, A.; Grandi, G.; Mckinnon, B.; Bolla, D.; Mueller, M. D.
abstract
Background/aims: Laparoscopy is an established, safe, and feasible management option for tubal pregnancies, even in women with significant hemoperitoneum. In case of interstitial pregnancy, however, a laparoscopic surgical approach is still a matter of debate. The objective of this study is to evaluate the safety and feasibility of a laparoscopic approach to interstitial pregnancies. Methods: A total of 92 women with ectopic pregnancy who underwent a surgical management from April 2009 to August 2015 were reviewed. Clinical and surgical outcomes of confirmed interstitial pregnancies (n = 10) (IP group) were compared with those of “more distal” tubal pregnancies (n = 79) (TP group). Results: Although there were no differences between the two groups in gestational age, ß-hCG values were significantly higher in the IP group (p = 0.005). All patients with IP were treated by laparoscopic wedge resection. The rate of surgical complications (p = 0.413) and subsequent MTX treatment (p = 0.531) were not significantly different between groups. Operating room (OR) time (p = 0.007) was higher in the IP than in the TP group. After stratification for the presence of hemoperitoneum this difference remained, with patients in the IP group having longer OR time (p = 0.034) and additionally higher intra-operative blood loss (EBL) (p = 0.013). On the other hand, in the absence of hemoperitoneum no differences between the two groups were observed. Conclusions: In experienced hands, the laparoscopic management of interstitial pregnancies seems to be as safe and feasible as that of other tubal pregnancies. However, it could be technically more challenging, especially in case of hemoperitoneum.
2017
- PET/CT guided surgical excision of small abdominal wall metastases in morbidly obese endometrial cancer patients
[Articolo su rivista]
Papadia, A.; Nirgianakis, K.; Gasparri, M. L.; Grandi, G.; Bolla, D.; Klaeser, B.; Mueller, M. D.
abstract
2017
- The Jellyfish Sign: A New Sonographic Cervical Marker to Predict Maternal Morbidity in Abnormally Invasive Placenta Previa
[Articolo su rivista]
Bertucci, E.; Sileo, F. G.; Grandi, G.; Fenu, V.; Cani, C.; Mancini, L.; Mataca, E.; Facchinetti, F.
abstract
Purpose -To investigate the value of a new cervical sonographic sign, called the jellyfish sign (JS), for predicting the risk of maternal morbidity in cases of abnormally invasive placenta (AIP) previa totalis. Materials and Methods -Retrospective evaluation of transvaginal (TV) and transabdominal (TA) scans performed in all singleton pregnancies with placenta previa totalis. JS, i.e. the absence of the normal linear demarcation between the placenta previa and the cervix, was evaluated by TV scans. The presence/severity of AIP and outcomes of maternal morbidity were related to this sign. Results -JS was noted in 8/39 (20.5%) patients. The two analyzed groups, i.e. with and without JS, were similar. The specificity of JS in AIP diagnosis, histological findings of accreta/increta/percreta, need for caesarean hysterectomy or blood loss >2000ml ranges between 92% and 96.2%, with the PPV and NPV ranging between 71.4% and 85.7% and 61.3% and 80.6%, respectively. The JS group had a significant increase in blood loss (ml) (p=0.003), transfusions (%) (p=0.016), red blood cells (p=0.002) and plasma (p=0.002), admission to an postoperative intensive care unit (ICU) (%) (p=0.002), hospitalization length (p<0.001) and the need of cesarean hysterectomy (%) (p<0.001). JS was independently correlated to cesarean hysterectomy (OR 25.6; 95% CI 2.0:322.3, p=0.012) and blood loss >2000ml (OR 16.6; 95% CI 1.5:180.1, p=0.021) also in a logistic regression model. Conclusion -JS is useful in predicting the increase in maternal morbidity: massive transfusion, admission to the ICU and cesarean hysterectomy related to intraoperative bleeding in patients with a previa AIP.
2017
- The association between progestins, nuclear receptors expression and inflammation in endometrial stromal cells from women with endometriosis
[Articolo su rivista]
Grandi, Giovanni; Mueller, Michael D; Bersinger, Nick A; Facchinetti, Fabio; Mckinnon, Brett D.
abstract
Endometriosis is an inflammatory disease and nuclear receptors play a crucial role in mediating the inflammatory response. In endometrial stromal cells (ESC), nuclear receptors expression can be influenced by the local environment. Progestins are first-line, on-label treatments of endometriosis that may have direct effects on endometriotic lesions through these nuclear receptors. Therefore, we investigated whether there was an association between nuclear receptors expression and the influence of progestins on inflammatory cytokines production in a preliminary, in vitro study with primary cultures. ESC from endometrial biopsies of six subjects with histologically confirmed endometriosis were treated for 6 h with medium alone or with TNF-α (10 or 100 ng/ml) in the presence of dienogest (DNG), medroxyprogesterone acetate (MPA) and norethisterone acetate (NETA) 10-5 M. The progestin-mediated change in IL6, IL8 and MCP-1 mRNA transcription was measured, as was the PRA, PRB, GR, AR and MCR protein expression. The change (medium versus TNF-α 10 ng/ml and medium versus TNF-α 100 ng/ml) in IL6 mRNA transcription was positively associated with the change in PRB, but not PRA with both DNG and NETA treatment. The change in IL8 mRNA was negatively associated with AR expression in the presence of NETA. The change in MCP-1 mRNA expression was positively associated with GR expression and negatively associated with MCR after MPA treatment. The associations between the change in cytokines mRNA expression and nuclear receptors protein expression in response to progestins activity may indirectly suggest different activities of these compounds at a local level worthy of further investigations.
2017
- The impact of reproductive life on breast cancer risk in women with family history or BRCA mutation
[Articolo su rivista]
Toss, A.; Grandi, G.; Cagnacci, A.; Marcheselli, L.; Pavesi, S.; De Matteis, E.; Razzaboni, E.; Tomasello, C.; Cascinu, S.; Cortesi, L.
abstract
Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or conflicting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12-0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09-0.66; p = 0.005) or more (HR 0.25; 95% IC 0.08-0.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01-0.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy (HR 0.62; 95% IC 0.38-0.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42-0.85; p = 0.004) showed to be the main protective factors. Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are influenced by different protective and risk factors.
2017
- Vaginal alpha-lipoic acid shows an anti-inflammatory effect on the cervix, preventing its shortening after primary tocolysis. A pilot, randomized, placebo-controlled study
[Articolo su rivista]
Grandi, G.; Pignatti, L.; Ferrari, F.; Dante, G.; Neri, I.; Facchinetti, F.
abstract
Introduction: Inflammation might be an important underlying cause of preterm birth. Our aim is to explore whether vaginal administration α-lipoic acid reduces cervical inflammation and shortening after primary tocolysis. Materials and methods: Singleton pregnancies between 24–30 weeks remaining undelivered after hospitalization for preterm labor were randomly allocated to placebo (20 women, 15 analyzed) or vaginal ALA 400 mg (active ingredient 10 mg) daily (20 women, 17 analyzed) for 30 days. A cervical swab to quantify pro-inflammatory (IL1, IL2, IL6, IL8, TNFα) and anti-inflammatory (IL4, IL10) cytokines as well as transvaginal ultrasound cervical length measurement (CL) were performed before and after treatment. Results: The % changes of pro-inflammatory cytokines do not differ between treatment groups, while IL4 significantly increases by vaginal ALA in comparison to placebo (118.0 ± 364.3% versus 29.9 ± 103.5%, p = 0.012). Combined anti-inflammatory cytokines show same trend (292.5 ± 208.5% versus 64.5 ± 107.4, p = 0.03). CL remains similar in vaginal ALA group (from 23.1 ± 6.6 to 20.80 ± 7.9 mm), while it significantly decreased in placebo group (from 20.4 ± 6.5 to 13.8 ± 7.5 mm, p < 0.001 versus Baseline; p = 0.003 versus vaginal ALA). Conclusion: Vaginal ALA significantly stimulates anti-inflammatory ILs in the cervix of undelivered women after a preterm labor episode. This effect is associated with a stabilization of the CL.
2017
- Wide diameter immediate post-extractive implants vs delayed placement of normal-diameter implants in preserved sockets in the molar region: 1-year post-loading outcome of a randomised controlled trial
[Articolo su rivista]
Checchi, V; Felice, P; Zucchelli, G; Barausse, C; Piattelli, M; Pistilli, R; Grandi, G; Esposito, M
abstract
Purpose: To compare the effectiveness of 6.0 to 8.0 mm-wide diameter implants, placed immediately after tooth extraction, with conventional 4.0 or 5.0 mm diameter implants placed in a preserved socket after a 4-month period of healing in the molar region.Materials and Methods: Just after extraction of one or two molar teeth, and with no vertical loss of the buccal bone in relation to the palatal wall, 100 patients requiring immediate post-extractive implants were randomly allocated to immediate placement of one or two 6.0 to 8.0 mm-wide diameter implants (immediate group; 50 patients) or for socket preservation using a porcine bone substitute covered by a resorbable collagen barrier (delayed group; 50 patients), according to a parallel group design in one centre. Bone-to-implant gaps were filled with autogenous bone retrieved with a trephine drill used to prepare the implant sites for the immediate wide diameter post-extractive implants. Four months after socket preservation, one to two 4.0 or 5.0 mm-wide delayed implants were placed. Implants were loaded 4 months after placement with fixed provisional restorations in acrylic, and replaced after 4 months by fixed, definitive, metal-ceramic restorations. Patients were followed to 1 year after loading. Outcome measures were: implant failures, complications, aesthetics assessed using the pink esthetic score (PES), peri-implant marginal bone level changes, patient satisfaction, number of appointments and surgical interventions recorded, when possible, by blinded assessors.Results: Three patients dropped out 1 year after loading from the immediate group vs six from the delayed group. Five implants out of 47 failed in the immediate group (10.6%) vs two out 44 (4.6%) in the delayed group, the difference being not statistically significant (difference in proportion = 6.0%, 95% CI: -8.8% to 20.8%, P = 0.436). In the immediate group 10 patients were affected by 10 complications, while in the delayed group four patients were affected by four complications. The difference was not statistically significant (difference in proportion = 12%, 95% CI: -2% to 26%, P = 0.084). At delivery of the definitive prostheses, 4 months after loading, the mean total PES score was 9.65 +/- 1.62 and 10.44 +/- 1.47 in the immediate and delayed groups, respectively. At 1 year after loading, the mean total PES score was 9.71 +/- 2.71 and 10.86 +/- 1.37 in the immediate and delayed groups, respectively. The Total PES score was statistically significantly better at delayed implants both at 4 months (mean difference = 0.79; 95% CI: 0.05 to 1.53; P = 0.03) and at 1 year (mean difference = 1.15; 95% CI: 0.13 to 2.17; P = 0.02). Marginal bone levels at implant insertion (after bone grafting) were 0.04 mm for immediate and 0.11 mm for delayed implants, which was statistically significantly different (mean difference = 0.07; 95% CI: 0.02 to 0.12; P < 0.0001).One year after loading, patients in the immediate group lost on average 1.06 mm and those from the delayed group 0.63 mm, the difference being statistically significant (mean difference = 0.43 mm; 95% CI: 0.15 to 0.61; P < 0.0001). All patients were fully or partially satisfied both for function and aesthetics, and would undergo the same procedure again both at 4 months and 1 year after loading. Patients from the immediate group required on average 7.48 +/- 1.45 visits to the clinician and 2.14 +/- 0.49 surgical interventions and to have their definitive prostheses delivered vs 10.30 +/- 0.99 visits and 3.08 +/- 0.40 surgical interventions for the delayed group, the difference being statistically significant (P < 0.001 for visits, and P < 0.001 for surgical interventions).Conclusions: Preliminary 1 year follow-up data suggest that immediate placement of 6.0 to 8.0 mm wide diameter implants in molar extraction sockets yielded inferior aesthetic outcomes than ridge preservation and delayed placement of conventional 4.0 to 5.0 mm diameter implants.
2016
- A 10-year report from a multicentre randomised controlled trial: Immediate non-occlusal versus early loading of dental implants in partially edentulous patients
[Articolo su rivista]
Zuffetti, F.; Esposito, M.; Galli, F.; Capelli, M.; Grandi, G.; Testori, T.
abstract
RESULTS: Fifty-two implants were loaded immediately and 52 early. Three patients with 8 implants dropped out from the immediate group versus two patients with 3 implants from the early loaded group; all remaining patients were followed for at least 10 years after loading. One single immediately loaded implant failed 2 months after placement. Three patients with immediately loaded implants and two with early loaded implants were affected by complications. There were no statistically significant differences for implant/prosthesis failures (Fisher's exact test: P = 0.294; difference = 4%, 95% CI: -16% to 24%) and complications between groups (Fisher's exact test: P = 0.574; difference = 4.5%, 95% CI: -12% to 21%). Both groups gradually lost peri-implant bone in a highly statistically significant way at 2, 8 and 14 months, and at 4, 5 and 10 years. After 10 years, immediately loaded patients lost an average of 1.34 mm and early loaded patients lost 1.42 mm of peri-implant marginal bone. At 10 years, there was a statistically significant recession (P < 0.001) of the vestibular soft tissues from baseline (delivery of the final restorations 8 months after implant placement) at both immediate (0.38 mm) and early (0.25 mm) loaded implants. There were no statistically significant differences in terms of peri-implant bone (difference = 0.08 mm, 95% CI: -0.49 to 0.65; P = 0.49) and soft-tissue level changes (difference = 0.07 mm, 95% CI: -0.48 to 0.62; P = 0.469) between the two groups at 10 years after loading.CONCLUSIONS: In well-maintained patients, complications are uncommon and healthy and stable peri-implant tissues can be maintained for 10 years around both immediate and early loaded implants. Conflict-of-interest statement: This trial was independently designed and initiated by the investigators. BIOMET 3i, the manufacturer of the implants used in this investigation, provided partial economic support at a later stage, and finally ZIMMER-BIOMET partially supported the present publication, however data belonged to the authors and by no means did the sponsor interfere with the conduct of the trial or the publication of its results.PURPOSE: To compare peri-implant bone and soft-tissue levels of immediate non-occlusally loaded versus non-submerged early loaded implants in partially edentulous patients 10 years after loading.MATERIALS AND METHODS: Fifty-two patients were randomised in five Italian private practices: 25 in the immediately loaded group and 27 in the early loaded group. To be immediately loaded, single implants had to be inserted with a torque of at least 30 Ncm, and splinted implants with a torque of at least 20 Ncm. Immediately loaded implants were provided with non-occluding temporary restorations within 48 h. After 2 months, the provisional restorations were put in full occlusion. Implants were early loaded after 2 months. Definitive restorations were provided 8 months after implant placement. Outcome measures were prosthesis failures, implant failures and complications, recorded by non-blinded assessors, and peri-implant bone and soft-tissue levels evaluated by blinded assessors.
2016
- Adenomyosis of the Extrapelvic Portion of the Round Ligament
[Articolo su rivista]
Cagnacci, Angelo; Xholli, Anjeza; Grandi, Giovanni; Ficarra, Guido; Pecchi, Annarita
abstract
Background: Adenomyosis is a disease of the uterus characterized by invasion of endometrial cells within the myometrium. Adenomyosis is typically confined to the uterus, with no distant localizations. This article reports on a case of adenomyosis of the distal extrapelvic portion of the round ligament. Case: The patient, a 49-year-old woman, had previously undergone surgery for pelvic endometriosis. This prior surgery included removal of uterus, fallopian tubes, and a portion of the sigmorectal intestine. She then presented with a nodule on the right side of her pubis. The nodule was close to the upper part of her right labia majora. She was experiencing cyclic pain, nodule enlargement, and edema on the right side of her pubis. The entire round ligament, from the internal inguinal canal to its distal end above the pubis, was removed. Histology testing revealed that the distal nodule was a myomalike neoformation containing endometrial tissue; this was definable as adenomyosis. Results: After the surgical procedure, the patient recovered quickly and after 6 months she was still free of symptoms. Conclusions: To the current authors' knowledge, this is the first case describing such a distant migration of endometrial cells up to the final extraperitoneal end of the round ligament to form a nodule of adenomyosis. A physical examination and imaging should be performed to rule out hernia, a cyst of the Nuck's duct, or lymph-node enlargement. Complete excision is curative. (J GYNECOL SURG 32:204)
2016
- Body composition and resting metabolic rate of perimenopausal women using continuous progestogen contraception
[Articolo su rivista]
Napolitano, Antonella; Zanin, Renata; Palma, Federica; Romani, Cecilia; Grandi, Giovanni; Di CArlo, Costantino; Cagnacci, Angelo
abstract
Objective The effect on body composition and in particular on fat mass (FM) of
12 months ’ use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing
intrauterine system (LNG-IUS) was evaluated in women in the perimenopause.
Methods An observational study comprised 102 perimenopausal women: 42 received a
75 μ g DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body
composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and
again after 12 months.
Results FM did not change in the control group ( 0.5 1.6%) but signifi cantly increased
in the LNG-IUS group ( 1.1 2.9%; p 0.02 vs. controls) and in the DSG group
( 2.8 3.5%; p 0.0001 vs. controls; p 0.02 vs. LNG-IUS). Women treated with DSG or
the LNG-IUS showed a non-signifi cant increase in body weight, body mass index and waist
circumference. RMR did not signifi cantly vary in the control group ( 3.8 292.9 kJ/
24 h) and tended to decrease but not signifi cantly in the LNG-IUS (115.5 531.8 kJ/
24 h) and DSG groups (305.9 556.9 kJ/24 h).
Conclusions The results of this preliminary study seem to indicate that in perimenopausal
women continuous use of the DSG-only pill and to a lesser extent the LNG-IUS may
favour FM accumulation.
2016
- Dienogest mediates midkine suppression in endometriosis
[Articolo su rivista]
Nirgianakis, K; Grandi, Giovanni; Mckinnon, B.; Bersinger, N.; Cagnacci, Angelo; Mueller, M.
abstract
Study question: What are the effects of dienogest (DNG) on midkine (MK) production in women with endometriosis? summary answer: DNG-mediated down-regulation of MK in vivo and in vitro. what is known already: DNG is an oral progestin that alleviates painful symptoms of women with endometriosis with a favourable tolerability and safety profile. Its effects on MK, a growth factor that plays an important role in endometriosis, have not yet been investigated. study design, size, duration: Prospective in vivo study on 283 patients subjected to laparoscopy for benign pathologies in a University hospital and in vitro cultures of primary endometrial stromal cells (ESC) from6 of thesewomenwith histologically confirmed endometriosis. participants/materials, setting, methods: MK concentrations in the peritoneal fluid (PF) of women were measured by ELISA and compared based on endometriosis status and the use of DNG. A subsequent in vitro analysis with ESC was used to confirm the direct influence of DNG and other progestins including, norethisterone acetate (NETA) and medroxyprogesterone acetate (MPA) on MK mRNA production. main results and the role of chance: The final study population consisted of 253 women.Of these, 165 suffered fromendometriosis, with 62 of them taking DNG (DNG group) and 103 taking no hormone treatment (non-DNG group) during at least 3 months before surgery. Another 88 women were endometriosis free (non-endometriosis group). The concentration of MK was highest in the PF of women in the non-DNG group (median 5.26 ng/ml, IQR 2.74-8.46). Significantly lower concentrations were found in the non-endometriosis group (median 3.51 ng/ml, IQR: 1.90-7.53, P = 0.028). The lowest concentrationswere found in theDNGgroup (median 2.44 ng/ml, IQR: 1.12-4.70, P< 0.0001 versus non-DNG group, P = 0.048 versus non-endometriosis group). The treatment of primary cultured ESC with DNG (10-5 M) suppressed MK mRNA production (P = 0.016), whereas MPA (P = 0.109) and NETA (P = 0.422) at same concentrations did not show a similar effect. limitations, reasons for caution: The non-randomized design of the study. wider implications of the findings: These findings could indicate a direct effect ofDNGon endometriotic cells that could contribute to its effectiveness in the treatment of this disease. study funding/competing interest(s): Funding was received from Swiss National Science Foundation (Grant No. 320030-140774).M.D.M. has received fees for speaking at scientificmeetings fromBayer. The other authors have no conflicts of interest to declare. The authors state that the manufacturer of dienogest has in no way influenced the performance or outcomes of this study.
2016
- Does dienogest influence the inflammatory response of endometriotic cells? A systematic review
[Articolo su rivista]
Grandi, Giovanni; Mueller, Michael; Bersinger, Nick A.; Cagnacci, Angelo; Volpe, Annibale; Mckinnon, Brett
abstract
Objective and design: A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells. Main outcome measures: In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human). Results: After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue. These studies identified a modulation of prostaglandin (PG) production and metabolism (PGE2, PGE2 synthase, cyclo-oxygenase-2 and microsomal PGE synthase-1), pro-inflammatory cytokine and chemokine production [interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1 and stromal cell-derived factor-1], growth factor biosynthesis (vascular endothelial growth factor and nerve growth factor) and signaling kinases, responsible for the control of inflammation. Evidence supports a progesterone receptor-mediated inhibition of the inflammatory response in PR-expressing epithelial cells. It also indicated that DNG inhibited the inflammatory response in stromal cells, however, whether this was via a PR-mediated mechanism is not clear. Conclusions: DNG has a significant effect on the inflammatory microenvironment of endometriotic lesions that may contribute to its clinical efficacy. A better understanding of the specific anti-inflammatory activity of DNG and whether this contributes to its clinical efficacy can help develop treatments that focus on the inhibition of inflammation while minimizing hormonal modulation.
2016
- Hepatic resection during cytoreductive surgery for primary or recurrent epithelial ovarian cancer
[Articolo su rivista]
Gasparri, M. L.; Grandi, G.; Bolla, D.; Gloor, B.; Imboden, S.; Panici, P. B.; Mueller, M. D.; Papadia, A.
abstract
Purpose: Surgical cytoreduction remains a cornerstone in the management of patients with advanced and recurrent epithelial ovarian cancer. Parenchymal liver metastases determine stage VI disease and are commonly considered a major limit in the achievement of an optimal cytoreduction. The purpose of this manuscript was to discuss the rationale of liver resection and the morbidity related to this procedure in advanced and recurrent ovarian cancer. Methods: A search of the National Library of Medicine’s MEDLINE/PubMed database until March 2015 was performed using the keywords: “ovarian cancer,” “hepatic,” “liver,” and “metastases.” Results: In patients with liver metastases, hepatic resection is associated with a similar prognosis as stage IIIC patients. The length of the disease-free interval between primary diagnosis and occurrence of liver metastases, as well as residual disease after resection, is the most important prognostic factors. In addition, the number of liver lesions, resection margins, and the gynecologic oncology group performance status seem to play also an important role in determining outcome. Conclusions: In properly selected patients, liver resections at the time of cytoreduction increase rates of optimal cytoreduction and improve survival in advanced-stage and recurrent ovarian cancer patients.
2016
- Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry
[Articolo su rivista]
Cagnacci, Angelo; Bellafronte, Manuela; Xholli, Anjeza; Palma, Federica; Carbone, Maria Maddalena; Di Carlo, Costantino; Grandi, Giovanni
abstract
Objective: To evaluate the effect on ovarian reserve and blood flow of unilateral laparoscopic stripping of endometriotic versus non-endometriotic cysts.Design: Prospective observational study.Setting: Tertiary university gynecology unit.Patients: During the study period, 71 subjects underwent the first laparoscopic surgery for removal of a monolateral benign ovarian cyst.Interventions: Trans-vaginal ultrasound scans of the pelvis about six months after surgery.Main outcome measures: Ovarian volume, Antral Follicle Count (AFC) and Resistance Index (RI) of ovarian artery of the operated and the contralateral ovary.Results: Among 71 cysts, 39.4% were endometriotic and 60.6% non-endometriotic benign cysts. All the procedures were performed by the same experienced surgeons with a standardized technique. No major complications were reported during surgery. The mean (±SD) age and BMI of women were 31.0 ± 6.8 years and 24.2 ± 3.3 kg/m2, respectively. Mean diameter of the removed cysts was smaller for endometriotic than non-endometriotic cysts (4.35 ± 1.77 cm versus 6.33 ± 3.71 cm, p = 0.046). In comparison to non-operated, volume of the operated ovary was significantly lower and with a reduced AFC, with no difference between endometriotic and non-endometriotic cysts (-2.41 ± 2.35 versus -2.00 ± 2.23 cm3, p = 0.496) (-3.45 ± 3.07 versus -2.43 ± 1.95, p = 0.11). Ovarian artery RI was higher in the operated ovary with no difference between endometriotic and non-endometriotic cysts (0.19 ± 0.14 versus 0.14 ± 0.10, p = 0.455). The difference in ovarian volume (r = 0.178), AFC (r = 0.094) and RI (r = 0.079) between operated and non-operated ovary was not dependent on the diameter of the removed cyst.Conclusion: Ovarian surgery is associated with a decline of ovarian reserve, independently on the histological type and the diameter of the removed cyst.
2016
- Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis
[Articolo su rivista]
Grandi, Giovanni; Mueller, Michael D.; Papadia, Andrea; Kocbek, Vida; Bersinger, Nick A.; Petraglia, Felice; Cagnacci, Angelo; Mckinnon, Brett
abstract
Endometriosis is an estrogen-dependent disease characterised by the growth of endometrial epithelial and stromal cells outside the uterus creating a chronic inflammatory environment that further contributes to disease progression. The first choice treatment for endometriosis is currently progestin mediated hormone modulation. In addition to their progestogenic activity however, progestins also have the potential to bind to other nuclear receptors influencing their local activity on endometriotic cells. This local activity will be dependent on the steroid hormone receptor expression that occurs in endometrial cells in a chronic inflammatory environment. We therefore aimed to quantify receptors targeted by progestins in endometrial stromal cells after exposure to inflammation. Using primary endometrial stromal cells isolated from women with endometriosis we examined the mRNA and protein expression of the progesterone receptors A and B, membrane progesterone receptors 1 and 2, androgen receptors, mineralocorticoid receptors and glucocorticoid receptors after exposure to the inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). The results indicate that both cytokines reduced the expression of progesterone receptors and increased the expression of the glucocorticoid receptors in the endometrial stromal cells. The change in expression of progestin targets in endometrial stromal cells in an inflammatory environment could contribute to the progesterone resistance observed in endometriotic cells and ultimately influence the design of hormonal therapies aimed at treating this disease.
2016
- Metabolic impact of combined hormonal contraceptives containing estradiol
[Articolo su rivista]
Grandi, Giovanni; Napolitano, Antonella; Cagnacci, Angelo
abstract
Introduction: Is the replacement of ethinyl-estradiol (EE) with estradiol (E2) in combined hormonal contraceptives (CHCs) associated with fewer metabolic effects, leading to a further improvement on safety of hormonal contraceptives? Areas covered: This is a narrative review paper including all available data on the metabolic impact of CHCs containing E2 published in English up to December 2015. Modification of a metabolic variable of interest during the first months of treatment was considered as an outcome. Expert opinion: E2 was extensively used in oral contraceptives associated to nomegestrol acetate (NOMAc) in a monophasic 24 + 4 or its ester E2 valerate to dienogest (DNG) in a quadriphasic 26 + 2 regimen. The impact on the lipid metabolism and the hemostatic system of these preparations seems milder than that caused by EE-based ones, associated with no change of blood pressure. The impact on bone metabolism was instead similar to EE. Data available in the literature are mainly derived from studies having secondary minor metabolic outcomes as the primary end-point, and so currently not completely applicable on the real variables of interest (arterial or venous cardiovascular events, bone fractures). The preliminar parenteral use of E2 seems promising, both transdermal and vaginal, in particular after the introduction of a specific progestin with a high anti-ovulatory activity, like nestorone.
2016
- Progestin suppressed inflammation and cell viability of tumor necrosis factor-α-stimulated endometriotic stromal cells
[Articolo su rivista]
Grandi, Giovanni; Mueller, Michael; Bersinger, Nick; Papadia, Andrea; Nirgianakis, Konstatinos; Cagnacci, Angelo; Mckinnon, Brett
abstract
Problem: Endometriosis is an estrogen-dependent inflammatory disease. Progestins are a first-line treatment for endometriosis via activation of pituitary progesterone receptors and suppression of systemic estrogen: a less than optimal treatment. Increasing evidence is beginning to show that progestins may also influence local endometriotic cells, which may contribute to their clinical efficacy. Method of study: Endometrial stromal cells (ESC) isolated from women with endometriosis were cultured with TNF-α to simulate an inflammatory environment. ESC were treated with the progestins, medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), or dienogest (DNG) and cytokine mRNA production, protein secretion, and cell viability measured. Results: DNG, NETA, and MPA suppressed the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1 from ESC. DNG and NETA only reduced the TNF-α-stimulated mRNA production. All three progestins suppressed TNF-α-stimulated ESC proliferation. Conclusion: Progestins may influence endometriotic stromal cells altering the inflammatory microenvironment and their clinical efficacy.
2016
- TNFα-induced IKKβ complex activation influences epithelial, but not stromal cell survival in endometriosis
[Articolo su rivista]
Kocbek, V.; Grandi, G.; Blank, F.; Wotzkow, C.; Bersinger, N. A.; Mueller, M. D.; Kyo, S.; Mckinnon, B. D.
abstract
STUDY QUESTION: Can the activity of the IκB kinase (IKKβ) complex in endometriotic cells contribute to endometriotic lesion survival? SUMMARY ANSWER: There is a constitutive activity of the IKKβ catalytic complex in peritoneal and deeply infiltrating lesions that can influence epithelial, but not stromal cell viability. WHAT IS KNOWN ALREADY: Endometriotic lesions exist in an inflammatory microenvironment with higher local concentrations of cytokines, such as tumour necrosis factor α (TNFα). TNFα stimulates the activation of the IKKβ complex, an important nodal point in multiple signalling pathways that influence gene transcription, proliferation and apoptosis. However, few data on the regulation of IKKβ in endometriotic tissue are currently available. STUDY DESIGN, SIZE, DURATION: A retrospective analysis of endometriotic tissue from peritoneal, ovarian and deeply infiltrating lesions from 37 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Basal and activated (phosphorylated) IKKβ concentrations were analysed by western blotting and immunohistochemistry. The relationship between the expression and activation of these proteins and peritoneal fluid (TNFα) concentrations, measured via ELISA, was examined. A subsequent in vitro analysis of TNFα treatment on the activation of IKKβ and the effect on epithelial and stromal cell viability by its inhibition with PS1145 was also performed. MAIN RESULTS AND ROLE OF CHANCE: Levels of the phosphorylated IKKβ complex in endometriotic lesions had a significant positive correlation with peritoneal fluid TNFα concentrations. Phosphorylated IKKβ complex was more prevalent in peritoneal and deeply infiltrating endometriosis lesions compared with ovarian lesions. IKKβ was present in both epithelial and stromal cells in all lesions but active IKKβ was limited to epithelial cells. TNFα stimulated an increased expression of phosphorylated IKKβ and the inhibition of this kinase with PS1145 significantly influenced ectopic epithelial cells viability but not eutopic epithelial cells, or endometrial stromal cells. LIMITATIONS, REASONS FOR CAUTION: In vitro analysis on epithelial cells was performed with immortalized cell lines and not primary cell cultures and only low sample numbers were available for the study. WIDER IMPLICATIONS OF THE FINDINGS: The regulation of aberrant signalling pathways represents a promising yet relatively unexplored area of endometriosis progression. The IKKβ complex is activated by inflammation and is critical nodal point of numerous downstream kinase-signalling pathways, including NFκB (nuclear factor κB), mTOR (mammalian target of rapamycin) and BAD (Bcl2-antagonist of cell death). This study shows a significant relationship between peritoneal fluid TNFα and IKKβ activation in epithelial cells that will have significant consequences for the continued survival of these cells at ectopic locations through the regulation of downstream pathways. LARGE SCALE DATA: None. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Swiss National Science Foundation (Grant Number 320030_140774). The authors have no conflict of interest to declare.
2015
- Effect of oral contraceptives containing estradiol and nomegestrol acetate or ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea
[Articolo su rivista]
Grandi, Giovanni; Napolitano, Antonella; Xholli, Anjeza; Tirelli, Alessandra; Di Carlo, Costantino; Cagnacci, Angelo
abstract
Objective: To study the three cycles effect on primary dysmenorrhea of the monophasic 24/4
estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl-estradiol/chlormadinone
acetate (EE/CMA) oral contraceptive. The tolerability and the effect of both preparations on
metabolism and health-related quality of life were also evaluated.
Design: Prospective observational cohort study.
Setting: Tertiary gynecologic center for pelvic pain.
Patients: Subjects with primary dysmenorrhea requiring an oral contraceptive, who spontaneously
selected either E2/NOMAC (n¼20) or EE/CMA (n¼20).
Main outcome measures: Visual Analogue Scale (VAS) score for dysmenorrhea, Short Form-36
questionnaire for health-related quality of life, lipoproteins and days of menstrual bleeding
(withdrawal bleeding during oral contraceptive).
Results: Mean age and body mass index (BMI) were similar between the two groups. The final
analysis was performed on 34 women, 15 in E2/NOMAC and 19 in EE/CMA group. Compliance
with treatment was significantly higher with EE/CMA (100%) than E2/NOMAC (75%) (p¼0.02).
Both treatments significantly (p50.0001) reduced VAS of primary dysmenorrhea, similarly
(E2/NOMAC by a mean of 74.7%, EE/CMA by a mean of 78.4%; p¼0.973). Only E2/NOMAC
significantly increased SF-36 score (p¼0.001), both in physical (p¼0.001) and mental domains
(p¼0.004). The mean number of days of menstrual bleeding was significantly reduced in
E2/NOMAC group (from 4.86 ± 1.20 d to 2.64 ± 1.59 d, p¼0.0005 versus baseline, p¼0.007
versus EE/CMA group). BMI did not vary in either group. E2/NOMAC did not change
lipoproteins and apoproteins while EE/CMA increased total cholesterol (p¼0.0114), HDLcholesterol
(p¼0.0008), triglycerides (p¼0.002), apoprotein-A1 (Apo-A1; p¼0.0006) and
apopoprotein-B (Apo-B; p¼0.008), decreasing LDL/HDL ratio (p¼0.024).
Conclusions: Both oral contraceptives reduced similarly primary dysmenorrhea, with E2/NOMAC
also reducing withdrawal bleedings and being neutral on lipid metabolism.
2015
- Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes
[Articolo su rivista]
Toss, Angela; Tomasello, Chiara; Razzaboni, Elisabetta; Contu, Giannina; Grandi, Giovanni; Cagnacci, Angelo; Schilder, Russel; Cortesi, Laura
abstract
More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality
is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with
hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in
the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51,
BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is
relevant for the future development ofmolecular diagnostic strategies and targeted therapeutic approaches.The recent development
and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyzemultiple
cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the
identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk
management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On
the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and
guide treatment decision-making.
2015
- Immediate loading of post-extractive versus delayed placed single implants in the anterior maxilla: Outcome of a pragmatic multicenter randomised controlled trial 1-year after loading
[Articolo su rivista]
Esposito, M.; Barausse, C.; Pistilli, R.; Jacotti, M.; Grandi, G.; Tuci, L.; Felice, P.
abstract
Purpose: To compare the effectiveness of immediate post-extractive single implants with delayed implants, placed in preserved sockets after 4 months of healing. Implants that achieved an insertion torque of at least 35 Ncm were immediately non-occlusally loaded. Materials and methods: Just after tooth extraction, and in the presence of less than 4 mm of vertical loss of the buccal bone in relation to the palatal wall, 106 patients requiring a single immediate post-extractive implant in the maxilla from second to second premolar were randomly allocated to immediate implant placement (immediate group; 54 patients) or to socket preservation using anorganic bovine bone covered by a resorbable collagen barrier (delayed group; 52 patients), according to a parallel group design at three different centres. Bone-to-implant gaps were to be filled with anorganic bovine bone, however this was not carried out in 17 patients (corresponding to 40% of those who should have been grafted). Four months after socket preservation, delayed implants were placed. Implants inserted with an insertion torque of at least 35 Ncm were immediately loaded with non-occluding provisional single crowns, then replaced after 4 months by definitive crowns. Patients were followed up to 1 year after loading. Outcome measures were implant failures, complications, aesthetics assessed using the pink esthetic score (PES), peri-implant marginal bone level changes and patient satisfaction recorded by blinded assessors. Results: Nineteen (35%) implants were not immediately loaded in the immediate group versus 39 (75%) implants in the delayed placement group because an insertion torque superior to 35 Ncm could not be obtained. Six patients dropped out 4 months after loading from the delayed group versus none in the immediate group. Two implants failed in the immediate group (6%) versus none in the delayed group, with the difference showing no statistical significance (difference in proportions = 0.04; 95% CI: -0.03 to 0.11; P = 0.187). Eight minor complications occurred in the immediate group and one in the delayed group, and this was statistically significant (difference in proportions = 0.13; 95% CI: 0.03 to 0.23; P = 0.028). At delivery of definitive crowns, 4 months after loading, the mean aesthetic score was 12.8 and 12.6 in the immediate and delayed groups, respectively. At 1 year after loading, the mean aesthetic score was 13.0 and 12.8 in the immediate and delayed groups, respectively. There was no statistically significant difference at 4 months (P = 0.500) and at 1 year (P = 0.615). Marginal bone levels at implant insertion (after bone grafting) were 0.10 mm for immediate implants and 0.02 mm for delayed implants, which did not have a statistically significantly difference (mean difference = 0.08; 95% CI: 0.04 to 0.12; P < 0.001). One year after loading, patients of the immediate group lost on average 0.23 mm and those in the delayed.
2015
- Immediate, early (3 weeks) and conventional loading (4 months) of single implants: Preliminary data at 1 year after loading from a pragmatic multicenter randomised controlled trial
[Articolo su rivista]
Grandi, T.; Guazzi, P.; Samarani, R.; Tohme, H.; Khoury, S.; Sbricoli, L.; Grandi, G.; Esposito, M.
abstract
Purpose: To compare the clinical outcome of single implants which underwent immediate nonocclusal loading with implants subjected to early non-occlusal loading at 3 weeks, and implants conventionally loaded at 4 months. Materials and methods: One hundred and five patients in five private practices requiring a single implant-supported crown were randomised to immediate loading (35 patients), early loading (35 patients) and conventional loading (35 patients) groups. To be immediately or early loaded, implants had to be inserted with a torque superior to 45 Ncm. Immediately and early loaded implants received non-occluding temporary crows, whereas conventionally loaded implants were directly restored with definitive crowns. Temporary crowns were replaced by definitive ones after 4 months. Outcome measures were crown and implant failures, complications and peri-implant marginal bone level changes recorded by a blinded assessor. Results: Two patients dropped out from the immediate loading group up to 1-year post-loading. Two implants failed, one in the immediately loaded and one in the early loaded group (P = 0.601). One immediately loaded implant and two early loaded implants were affected by one complication each (P = 0.162). Mean peri-implant marginal bone loss after 1 year was -0.120 ± 0.230 mm (95% CI -0.35, 0.10) for immediate, -0.390 ± 0.840 mm (95% CI -1.23, 0.45) for early and -0.201 ± 0.306 mm (95% CI -0.51; 0.11) for conventionally loaded implants. There were no statistically significant differences for any of the outcome measures between the three loading strategies up to 1-year post-loading. Conclusions: No major clinical differences were observed with regard to implant survival, complications and marginal bone level changes when loading single implants immediately, early or conventionally. Conflict-of-interest statement: This trial was partially funded by JDentalCare, the manufacturer of the implants evaluated in this investigation, however data belonged to the authors and by no means did the manufacturer interfere with the conduct of the trial or the publication of the results. Dr Tommaso Grandi, Paolo Guazzi, Rawad Samarani and Marco Esposito are consultants for JDentalCare.
2015
- Immediately loaded machined versus rough surface dental implants in edentulous jaws: One-year postloading results of a pilot randomised controlled trial
[Articolo su rivista]
Esposito, M.; Felice, P.; Barausse, C.; Pistilli, R.; Grandi, G.; Simion, M.
abstract
Purpose: To compare the effectiveness of immediately loaded total prostheses supported by implants with a roughened surface versus implants with a machined/turned surface. Materials and methods: Fifty edentulous or to-be-rendered edentulous patients requiring an implant-supported cross-arch prosthesis, were randomised either to receive four to eight implants with a roughened surface (25 patients) or with a machined/turned surface (25 patients). Provisional metal-reinforced acrylic prostheses were delivered 48 h after implant placement. Provisional prostheses were replaced after 4 months, by definitive screw-retained metal-resin cross-arch restorations. Outcome measures were prosthesis and implant failures, any complications and peri-implant marginal bone level changes. Patients were followed 1 year after loading. Results: One year after loading no patient dropped out. No prosthesis failed, but two machined implants were found to be mobile at definitive impression taking in 1 patient (Fisher's exact test: P = 0.312; difference in proportions = 4%; 95% Cl: -10 to 18). No complications occurred. Both groups presented a significant peri-implant marginal bone loss at 1 year after loading (P < 0.0001), -0.64 ± 0.20 mm for rough implants and -0.68 ± 0.23 mm for turned implants, respectively, with no statistically significant differences between the two groups (P = 0.482; mean difference = 0.04 mm; 95% Cl: -0.17 to 0.25). Conclusions: Up to 1 year after immediate loading, both implant surfaces provided good and similar results, however, the only two implants which failed early in the same patient had a machined surface. These preliminary results must be confirmed by larger trials with longer follow-ups. Conflict-of-interest statement: I-RES, the manufacturer of the implants used in this study, donated their implants and prosthetic components, however, data property belonged to the authors and by no means did I-RES interfere with the conduct of the trial or the publication of its results.
2015
- Implant site preparation using a single bur versus multiple drilling steps: 4-month post-loading results of a multicenter randomised controlled trial
[Articolo su rivista]
Guazzi, P.; Grandi, T.; Grandi, G.
abstract
Purpose: To compare the clinical outcome of implants inserted in sites prepared with a simplified protocol consisting of one single drill versus multiple conventional drilling steps. Materials and methods: In two private clinics, 40 patients, requiring one single implant and having a residual bone height of at least 10 mm and a thickness of at least 5 mm measured on computerised tomography (CT) scans, were randomised after flap elevation to have the implant site prepared using a single drilling step with a newly designed tapered-cylinder drill (1-drill group) or a conventional procedure with multiple drills (multiple-drill group). Implants were left to heal non-submerged for 3 months and then they were loaded with a final metal-ceramic crown. Outcome measures were: implant failure; any complications; peri-implant marginal bone level changes assessed by a blinded outcome assessor operation time; operator preference and post-surgical pain, swelling and analgesic consumption. All patients were followed up to 4 months after implant loading. Results: Twenty patients were randomised to the 1-drill group and 20 patients to the multiple-drill group. No implant failed and no complications occurred. Four months after loading, implants in the 1-drill group lost 0.54 mm of peri-implant bone versus 0.41 mm for the implants in the multiple-drill group. There were no statistically significant differences for marginal bone level changes between the two groups (difference 0.13 mm, 95% CI -0.21; 0.47, P = 0.108). Less time which was statistically significant (3.66 mins, 95% CI 2.69; 4.63, P < 0.0001) was required to place the implant with the single bur. Both operators always preferred the single bur technique. Postoperatively, patients in the 1-drill group vs patients in the multiple-drill group reported statistically significant differences for pain level (difference 27.5, 95% CI 3.3; 51.7, P < 0.0001), number of days in which the swelling persisted (difference 3.4, 95% CI 2.4; 4.4, P < 0.0001) and the number of analgesic drugs taken (difference 2.8, 95% CI 1.4; 4.2, P < 0.0001) Conclusions: Within the limits of this trial, both drilling techniques produced successful results over a 4-month post-loading follow-up period, but the single bur procedure required less surgical time and lead to less postoperative morbidity. Conflict-of-interest statement: Dr Paolo Guazzi and Dr Tommaso Grandi served as consultants for JDentalCare. This study was completely self-financed and no funding was sought or obtained, not even in the form of free materials.
2015
- Pelvic Pain and Quality of Life of Women With Endometriosis During Quadriphasic Estradiol Valerate/Dienogest Oral Contraceptive. A Patient-Preference Prospective 24-Week Pilot Study
[Articolo su rivista]
Grandi, Giovanni; Xholli, Anjeza; Napolitano, Antonella; Palma, Federica; Cagnacci, Angelo
abstract
The progestin dienogest (DNG) given alone effectively reduces pelvic pain of women with endometriosis. It is not clear whether the same occurs when DNG is associated with estradiol (E2).
2015
- Reproductive risk factors in women with family history of breast cancer attending an Italian Family Cancer Clinic
[Abstract in Rivista]
Toss, Angela; Grandi, Giovanni; Marcheselli, Luigi; DE MATTEIS, Elisabetta; Razzaboni, Elisabetta; Tomasello, Chiara; Cagnacci, Angelo; Cortesi, Laura
abstract
The investigation performed in women at a 3 times higher risk of breast cancer (RER3) shows that use of oral contraceptives was not associated with an increased risk of developing breast cancer.
2015
- Safety and effectiveness of early loaded maxillary titanium implants with a novel nanostructured calcium-incorporated surface (Xpeed): 3-year results from a pilot multicenter randomised controlled trial
[Articolo su rivista]
Felice, P.; Grusovin, M. G.; Barausse, C.; Grandi, G.; Esposito, M.
abstract
Purpose: To evaluate clinical safety and effectiveness of a novel calcium-incorporated titanium implant surface (Xpeed, MegaGen Implant Co., Gyeongbuk, South Korea). Materials and methods: Sixty patients were randomised to receive one to six implants in the maxilla with either calcium-incorporated (Xpeed) or control resorbable blasted media (RBM) surfaces, according to a parallel group design at two centres. Implants were submerged and exposed at three different endpoints in equal groups of 20 patients, each at 12, 10 and 8 weeks, respectively. Within 2 weeks, implants were functionally loaded with provisional or definitive prostheses. Outcome measures were prosthesis failures, implant failures, any complications and peri-implant marginal bone level changes. Results: Thirty patients received 45 calcium-incorporated implants and 30 patients received 42 control titanium implants. Three years after loading four patients dropped-out from the Xpeed group and one from the RBM group. No prosthesis or implant failures occurred. There were no statistically significant differences between the groups for complications (P = 0.91; difference in proportions = 0.79 %; 95% CI -0.71 to 2.29) and mean marginal bone level changes (P = 0.88; mean difference = -0.02 mm; 95% CI -0.26 to 0.22). Conclusions: Both implant surfaces provided good clinical results and no significant difference was found when comparing titanium implants with a nanostructured calcium-incorporated surface versus implants with RBM surfaces. Conflict-of-interest statement: MegaGen partially supported this trial and donated the implants and prosthetic components. The study design was negotiated with MegaGen Implant Co. (Gyeongbuk, South Korea), however, data property belonged to the authors and by no means did MegaGen interfere with the conduct of the trial or the publication of its results.
2015
- Short implants versus bone augmentation for placing longer implants in atrophic maxillae: One-year post-loading results of a pilot randomised controlled trial
[Articolo su rivista]
Esposito, M.; Barausse, C.; Pistilli, R.; Sammartino, G.; Grandi, G.; Felice, P.
abstract
Purpose: To evaluate whether short (5.0 to 8.5 mm) dental implants could be a suitable alternative to longer (at least 11.5 mm-long) implants placed in atrophic maxillae augmented with autogenous bone for supporting dental prostheses. Materials and methods: Twenty-eight patients with fully edentulous atrophic maxillae, whom had 5 to 9 mm of residual crestal bone height which was at least 5 mm thick, measured using computerised tomography (CT) scans, were randomised into two groups either to receive 4 to 8 short (5.0 to 8.5 mm) implants (15 patients) or autogenous bone from the iliac crest to allow the placement of at least 11.5 mm-long implants (13 patients). Bone blocks and the windows at the maxillary sinuses were covered with rigid resorbable barriers. Grafts were left to heal for 4 months before placing implants which were submerged. After 4 months, provisional reinforced acrylic prostheses or bar retained overdentures were delivered. Provisional prostheses were replaced, after 4 months, by definitive screw-retained metal-resin cross-arch restorations. Outcome measures were prosthesis and implant failures, any complications, peri-implant marginal bone level changes and patient satisfaction. Patients were followed up to 1 year after loading. Results: All patients were rehabilitated with implant-supported prostheses but two patients dropped out from the augmented group. One bilateral sinus lift procedure failed for infection, although short implants could be placed. One implant failed in the augmented group versus two short implants in two patients (Fishers exact test P = 1.00; difference in proportions = 0.06; 95% CI -0.28 to 0.17). All failures occurred before loading. Significantly more complications occurred in augmented patients: eight complications occurred in 5 augmented patients (all of them complained of pain 1 month after bone harvesting from the iliac crest) versus no complications in the short implant (Fisher's exact test P = 0.013; difference in proportions = 0.38; 95% CI 0.11 to 0.65). Both groups presented a significant peri-implant marginal bone loss at 1 year after loading (P < 0.0001); -1.05 (0.20) mm for short implants and -1.01 (0.16) mm for the augmented group, respectively, with no statistically significant differences between the two groups (mean difference -0.04 mm; 95% CI -0.22 to 0.14; P = 0.59). All patients were fully satisfied with the treatment and would have it again. Conclusions: This pilot study suggests that short implants may be a suitable, cheaper and faster alternative to longer implants placed in bone augmented with autogenous bone for rehabilitating edentulous atrophic maxillae, however, these preliminary results need to be confirmed by larger trials with follow-ups of at least 5 years.
2015
- The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life
[Articolo su rivista]
Grandi, Giovanni; Toss, Angela; Cortesi, Laura; Botticelli, Laura; Volpe, Annibale; Cagnacci, Angelo
abstract
Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly
confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation
in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last
cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the
inhibition of ovulation and menstruation.The step by step process of transformation fromtypical endometrioma, through atypical
endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific
molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes
PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid
ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased
by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible
preventive strategies during reproductive life.
2014
- Intensity of menstrual pain and estimated angle of uterine flexion
[Articolo su rivista]
Cagnacci, Angelo; Grandi, Giovanni; Cannoletta, Marianna; Xholli, Anjeza; Piacenti, Ilaria; Volpe, Annibale
abstract
To assess the impact of ultrasound-estimated uterus position on the intensity of pelvic pain.
2014
- Modification of body composition and metabolism during oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol
[Articolo su rivista]
Grandi, Giovanni; Piacenti, Ilaria; Volpe, Annibale; Cagnacci, Angelo
abstract
To observe the influence on metabolism and body composition of two oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol (EE).
2014
- One abutment-one time versus a provisional abutment in immediately loaded post-extractive single implants: A 1-year follow-up of a multicentre randomised controlled trial
[Articolo su rivista]
Grandi, T.; Guazzi, P.; Samarani, R.; Maghaireh, H.; Grandi, G.
abstract
Purpose: To compare immediately loaded post-extractive single implants using a definitive abutment versus provisional abutment later replaced by custom-made abutment. Materials and methods: In two private clinics, 28 patients in need of one single post-extractive implant in the maxilla or mandible from the left second premolar to the right second premolar area were randomised shortly before tooth extraction to provisional abutment (PA) and definitive abutment (DA) groups. Three patients had to be excluded for buccal wall fracture after tooth extraction. In the PA group, implants were immediately restored using a platform-switched provisional titanium abutment and definitive platform-switched titanium abutments were used in the DA group. In both groups, a non-occluding provisional single crown was provided. Implants were definitively restored after 4 months. In the PA group, the abutment was removed and the impression was made directly on the implant platform. In the DA group an impression of the abutment was made using a retraction cord. Outcome measures were: implant failures; complications; and marginal peri-implant bone level changes. Patients were followed up to 1 year after loading. Results: Twelve patients were randomised to the DA group and 13 patients to the PA group. At the 12-month follow-up, no implant failed. One biological complication occurred in the DA group and one mechanical complication occurred in the PA group. All complications were successfully treated. One year after loading, implants in the DA group lost an average of 0.11 mm (SD: 0.06) of periimplant bone and implants in PA group about 0.58 mm (SD: 0.11). At the 12-month follow-up, there was a statistically significant difference in bone level change between groups (mean difference: 0.48 mm, CI 95% 0.40; 0.55, P < 0.0001). Conclusions: Within the limits of this study, the non-removal of abutments placed at the time of surgery resulted in the maintenance of 0.5 mm more bone levels around immediately restored postextractive single implants than repeated abutment removal, although this amount of bone maintenance may not have a clinical impact Con?icts of interest noti?cation: Dr Tommaso Grandi and Dr Paolo Guazzi serve as consultants for JDentalCare. This study was completely self-?nanced and no funding was sought or obtained, not even in the form of free materials.
2014
- Pharmacokinetic evaluation of desogestrel as a female contraceptive
[Articolo su rivista]
Grandi, Giovanni; Cagnacci, Angelo; Volpe, Annibale
abstract
Desogestrel (DSG) is a third-generation 19-nortestosterone derivative progestogen. It is contained in many oral contraceptive preparations, both combined (COCs) to ethinyl-estradiol (EE) or alone in a progestin-only pill (POP). Its principal metabolite (etonogestrel, ETN) is the only progestin used for intravaginal combined contraception and one of the most used for subdermal hormonal contraception.
2014
- Prospective measurement of blood pressure and heart rate over 24 h in women using combined oral contraceptives with estradiol
[Articolo su rivista]
Grandi, Giovanni; Xholli, Anjeza; Napolitano, Antonella; Piacenti, Ilaria; Bellafronte, Manuela; Cagnacci, Angelo
abstract
Combined oral contraceptives (COCs) containing ethinyl-estradiol are known to increase blood pressure (BP). We evaluated whether COCs containing estradiol (E2) influence 24-h ambulatory BP and heart rate (HR) in normotensive and normal-weight women.
2013
- A 3-year report from a multicentre randomised controlled trial: Immediately versus early loaded implants in partially edentulous patients
[Articolo su rivista]
Grandi, T.; Guazzi, P.; Samarani, R.; Grandi, G.
abstract
Purpose: To compare implant failure, prosthesis failure and radiographic bone level changes of immediate non-occlusal loading versus early loading in partially edentulous patients 3 years after implant placement. Materials and methods: A total of 80 patients with partial edentulism were selected for a two implant-supported immediate restoration and randomised to immediate loading (test group) or early loading (control group) after 2 months, 40 patients for each group. To be included in the study, implants had to be inserted with a torque =30 Ncm. In the test group, implants were provided with non-occluding temporary restorations. In the control group, healing abutments were attached and implants were left to heal nonsubmerged. Definitive prostheses were delivered 2 months after surgery with full occlusal contacts. The outcome variables were implant failure, prosthesis failure, complications and radiographic bone level changes at implants 3 years after loading. The assessor was blinded to group assignment. Results: Eighty-one implants were immediately loaded and 80 were early loaded. Two immediately loaded patients and 1 early loaded patient dropped out at 3 years. No implant failed. Two complications occurred in the immediate loading group and 1 in the early loading group. There were no significant differences in bone levels changes at 36 months between the two groups (P = 0.67; difference 0.2 mm; 95% CI -0.23, 0.63). Immediately loaded implants lost 0.90 mm (95% CI 0.63, 1.17) and early loaded implants 1.10 mm (95% CI 0.81, 1.39). Conclusion: If adequate primary stability was achieved, no statistically significant difference in failure rates, complications or bone level changes between implants loaded immediately or early were observed 3 years after placement in partially edentulous patients.
2013
- Clinical outcome and bone healing of implants placed with high insertion torque: 12-month results from a multicenter controlled cohort study
[Articolo su rivista]
Grandi, T.; Guazzi, P.; Samarani, R.; Grandi, G.
abstract
This study evaluated the clinical outcome and the crestal bone resorption of implants placed with high insertion torque (up to 80 N cm). 102 patients were treated with 156 tapered implants. 42 implants (control group) presented insertion torque between 30 and 45 N cm (mean = 37.4 SD 8.2). 114 implants (experimental group) were placed with insertion torque between 50 and 80 N cm (mean = 74.8 SD 7.9). All implants were early loaded after 2 months. Peri-implant marginal bone levels were assessed immediately after surgery, and at 6- and 12-month follow up examinations. At the 12-month follow up all implants were clinically stable. After 12 months, patients in the experimental group lost an average of 0.41 mm (CI 95% 0.522; 0.263) of crestal bone compared with 0.45 mm (CI 95% 0.561; 0.286) for those in the control group. There were no significant differences between the two groups. No direct or inverse relationship was observed between the insertion torque values and crestal bone resorption. The results show that the use of high insertion torque (up to 80 N cm) did not prevent osseointegration and did not increase bone resorption around tapered implants early loaded up to 1 year after implant placement. © 2012 International Association of Oral and Maxillofacial Surgeons.
2013
- Immediate provisionalisation of single postextractive implants versus implants placed in healed sites in the anterior maxilla: 1-year results from a multicentre controlled cohort study
[Articolo su rivista]
Grandi, T.; Guazzi, P.; Samarani, R.; Grandi, G.
abstract
Purpose: The purpose of the study was to compare the clinical and aesthetic outcome of single postextractive implants versus implants placed in a preserved socket after 4 months of healing in the anterior maxilla. All of the implants were immediately non-occlusally loaded. Materials and methods: A total of 50 patients were treated in the two groups of study. The Delayed Group had a maxillary tooth (premolar, canine, lateral or central incisor) removed, with immediate socket grafting, followed by implant placement and provisionalisation 4 months later. The Immediate Group had immediate implant placement and provisionalisation. Outcome measures were implant failures, biological and biomechanical complications, peri-implant radiographic bone level changes, and gingival aesthetics. Results: At the 12-month follow-up, two implants failed in the Immediate Group (8%) versus one in the Delayed Group (4%), with a comparable rate of implant failure (P = 0.55). No complications occurred for either group. The 12-month peri-implant bone resorption was similar in both groups (P = 0.23): 0.71 mm (95% CI 0.45, 0.97) in the Immediate Group versus 0.60 mm (95% CI 0.38, 0.82) in the Delayed Group. The mean difference in bone resorption was 0.13 mm (95% CI -0.21, 0.47). An ideal gingival marginal level was reached most frequently in the Delayed Group (83.3% versus 52.1%, P = 0.04). Rates of full closure of the papilla were similar between the two groups (82.6% for the Immediate Group versus 62.5% for the Delayed Group, P = 0.12). Conclusions: Given the limitation that this was not a randomised controlled trial, there were no differences in complications or crestal bone response at immediate post-extractive implants when compared to delayed implants. A delayed protocol might be considered in the aesthetic zone due to the gingival recession that occurs after post-extractive implant placement.
2013
- Intermenstrual pelvic pain, quality of life and mood
[Articolo su rivista]
Grandi, Giovanni; Xholli, Anjeza; Ferrari, Serena; Cannoletta, Marianna; Volpe, Annibale; Cagnacci, Angelo
abstract
BACKGROUND/AIMS:
To investigate the independent importance of different types of pelvic pain on quality of life and depressive symptoms.
METHODS:
A cross-sectional study was performed on patients with pelvic pain. A 10-cm visual-analogue scale (VAS) was used to investigate intensity of intermenstrual pelvic pain, dysmenorrhea or deep dyspareunia. The SF-36 form and the Zung Self-Rating Scale for Depression (SDS) were used to investigate quality of life and depressive symptoms, respectively.
RESULTS:
The final study group consisted of 248 patients, 175/248 (70.6%) with intermenstrual pelvic pain, 46/248 (18.5%) with dysmenorrhea and 27/248 (10.9%) with deep dyspareunia associated or not with dysmenorrhea. Mean VAS score for dysmenorrhea was higher than that for deep dyspareunia (p < 0.003) and intermenstrual pelvic pain (p < 0.0001). Women with intermenstrual pelvic pain had the worst SF-36 (p < 0.0001) and SDS (p < 0.002) scores. SF-36 was independently and inversely related to intermenstrual pelvic pain (CR -1.522; 95% CI -2.188 to -0.856; p < 0.0001), and less strongly to dysmenorrhea (CR -0.729; 95% CI -1.487 to 0.030; p = 0.06). Indeed, only the physical component summary of SF-36 was independently related to dysmenorrhea (CR -0.956; 95% CI -1.783 to -0.129; p = 0.024). The SDS score was independently related only to intermenstrual pelvic pain (CR 0.573; 95% CI 0.241-0.904; p = 0.0008).
CONCLUSIONS:
Patients with intermenstrual pelvic pain have the worst SF-36 and SDS scores. Intermenstrual pelvic pain seems to be more strongly associated with a reduced quality of life and depressive mood.
2012
- Fattori di rischio cardiovascolare, dolore mestruale e qualità di vita con contraccettivi orali contenenti estradiolo valerato/dienogest vs etinilestradiolo/clormadinone acetato: trial prospettico, randomizzato.
[Altro]
Grandi, G; Cannoletta, M; Xholli, A; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2012
- Immediate loading of four (all-on-4) post-extractive implants supporting mandibular cross-arch fixed prostheses: 18-month follow-up from a multicentre prospective cohort study
[Articolo su rivista]
Grandi, T.; Guazzi, P.; Samarani, R.; Grandi, G.
abstract
Aim: To evaluate the outcome of immediately loaded mandibular cross-arch prostheses according to the 'all-on-4' concept supported by implants placed in fresh extraction sockets up to 18 months after loading. Materials and methods: In total, 47 patients with a mean age of 62.3 years (range 52 to 78) were rehabilitated with an immediately loaded fixed cross-arch prosthesis supported by four post-extractive implants. A total of 188 implants were inserted. Patients received a provisional fixed dental prosthesis with a metal framework within 48 hours after surgery and a permanent one 6 months later. The patients were evaluated clinically and radiographically at implant placement and at 6-, 12- and 18-month follow-up examinations. Results: At the 18-month follow-up, no implant failed and all restorations were stable. Peri-implant bone levels amounted to 0.31 ± 0.12 mm after 6 months, 0.58 ± 0.112 mm after 12 months and 0.7 ± 0.107 mm after 18 months. No significant differences in bone loss were found between axially placed and tilted implants at the 6-month (0.06 mm; P = 0.115), the 12-month (0.12 mm; P = 0.062) and the 18-month follow-up (0.08 mm; P = 0.146). Three patients had a fracture of the provisional restoration, but all of the definitive prostheses remained stable throughout the study period without any complications. Conclusions: Within the limits of this study, it can be suggested that immediately loaded mandibular cross-arch fixed dental prostheses can be supported by four post-extractive implants, however larger and longer follow-ups are needed. Conflict-of-interest statement: Dr Tommaso Grandi and Dr Paolo Guazzi serve as consultants for JDentalCare. This study was completely self-financed and no funding was sought or obtained, not even in the form of free materials.
2012
- Immediate loading of two unsplinted implants retaining the existing complete mandibular denture in elderly edentulous patients: 1-year results from a multicentre prospective cohort study
[Articolo su rivista]
Grandi, T.; Guazzi, P.; Samarani, R.; Garuti, G.; Grandi, G.
abstract
Purpose: To evaluate the outcome of two freestanding implants immediately loaded retaining an existing mandibular complete denture in elderly edentulous patients up to 1 year after loading. Materials and methods: 42 patients with a mean age of 76.5 years (range 71 to 89) were selected for stabilising their mandibular complete denture with two implants placed mesial to the mandibular canine position bilaterally. Individual ball abutments were connected and torqued at 30 Ncm and the existing complete denture was immediately attached. No postoperative limitations to chewing function were given. The patients were evaluated clinically and radiographically at implant placement and at 6-and 12-month follow-up examinations. Results: At the 12-month follow-up no implant failed. Peri-implant bone resorption was 0.203 mm (CI 95% 0.322; 0.086) after 6 months and 0.298 mm (CI 95% 0.425; 0.173) after 12 months. Of the 42 cases, 3 had major prosthetic complications and 5 patients required minor extra maintenance appointments. Conclusions: Within the limits of this study, it can be suggested that the immediate loading of two unsplinted implants retaining the existing complete mandibular denture in elderly patients can result in favourable implant survival and peri-implant bone healing, however larger and longer follow-ups of 5 years or more are needed.
2012
- Lipid metabolism, insulin resistance, blood pressure and body composition with oral contraceptives containing astradiol valerato/dienogest vs ethinylestradiol/chlormadinone: a prospective, randomized trial.
[Altro]
Grandi, G; Palma, F; Ferrari, S; Xholli, A; Cannoletta, M; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2012
- Prevalence of menstrual pain in young women: what is dysmenorrhea
[Articolo su rivista]
Grandi, Giovanni; Ferrari, S; Xholli, A; Cannoletta, M; Palma, F; Romani, C; Volpe, Annibale; Cagnacci, Angelo
abstract
Objectives: This study aimed to determine the frequency of dysmenorrhea, as identified by different definitions, in a population of young women, and to investigate factors associated with this complaint.Materials and methods: A final group of 408 young women completed a self-assessment questionnaire. This was a cross-sectional analytical study.Results: Menstrual pain was reported by 84.1% of women, with 43.1% reporting that pain occurred during every period, and 41% reporting that pain occurred during some periods. Women with menstrual pain had an earlier menarche (P = 0.0002) and a longer menstrual flow (P = 0.006), and this group was characterized as having a higher prevalence of smokers (P = 0.031) and a lower prevalence of hormonal contraception users (P = 0.015). Pain intensity was correlated (r = 0.302, P < 0.0001) positively with menstrual flow length (CR = 0.336), history of abortions (CR = 3.640), and gynecological pathologies (CR = 0.948), and negatively with age at menarche (CR = –0.225), use of hormonal contraception (CR = –0.787), and history of gynecological surgery (CR = –2.115). Considering the parameters of menstrual pain, a need for medication, and inability to function normally (absenteeism from study or social activities) alone or together, the prevalence of dysmenorrhea is 84.1% when considering only menstrual pain, 55.2% when considering the association between menstrual pain and need for medication, 31.9% when considering the association between menstrual pain and absenteeism, and 25.3% when considering the association between menstrual pain, need for medication, and absenteeism (P < 0.0001). The probability of having more severe dysmenorrhea is directly related to pain intensity as measured by a visual analog scale, but does not coincide with it.Conclusion: Menstrual pain is a very common problem, but the need for medication and the inability to function normally occurs less frequently. Nevertheless, at least one in four women experiences distressing menstrual pain characterized by a need for medication and absenteeism from study or social activities
2011
- Molecole di adesione tissutale ed endometriosi
[Altro]
Xholli, A; Generali, M; Rivasi, F; Cannoletta, M; Grandi, G; Zanin, R; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2011
- Planning familiare e rischio di endometriosi in donne con dolore pelvico cronico
[Altro]
Grandi, G; Xholli, A; Cannoletta, M; Ferrari, S; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2011
- Prevalenza e caratteristiche del dolore mestruale in giovani donne
[Altro]
Grandi, G; Cannoletta, M; Xholli, A; Palma, F; Generali, M; Depietri, C; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2011
- Trattamento medico dell'endometriosi: progestinici e formulazioni estro-progestiniche
[Altro]
Cagnacci, Angelo; Grandi, G; Xholli, A; Depietri, C; Volpe, Annibale
abstract
-
2010
- Differenze nell’espressione delle molecole di adesione tissutale in donne affette da endometriosi
[Altro]
Generali, M; Rivasi, F; Cannoletta, M; Grandi, G; Xholli, A; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2010
- Hormonal Contraception in perimenopausal women
[Abstract in Rivista]
Cagnacci, Angelo; Ferrari, S; Tirelli, A; Zaninb, R; Grandi, G; Volpe, Annibale
abstract
-
2010
- Miglioramento della qualità di vita con contraccettivo orale in donne affette da dismenorrea primaria
[Altro]
Grandi, G; Matteo, G; Xholli, A; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2010
- Prevalenza e fattori di rischio di dismenorrea in studentesse universitarie italiane
[Altro]
Grandi, Giovanni; Generali, M; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2010
- Use of hormonal contraception in italian university students
[Abstract in Atti di Convegno]
Grandi, Giovanni; Generali, M; Volpe, Annibale; Cagnacci, Angelo
abstract
--
2009
- Eziologia del dolore pelvico cronico e qualità di vita.
[Altro]
Xholli, A; Grandi, G; Generali, M; Romani, C; Cazzato, L; Volpe, Annibale; Cagnacci, Angelo
abstract
-
2009
- Sintomi della menopausa; conseguenze a breve e a lungo termine.
[Altro]
Cagnacci, Angelo; Xholli, A; Grandi, G.
abstract
-
2009
- Soluzioni di design per viti di connessione implantare: studio agli elementi finiti.
[Abstract in Atti di Convegno]
Forabosco, Andrea; Grandi, Tommaso; Grandi, Giovanni; Giannetti, Luca; Bertoldi, Carlo
abstract
Vedi allegato