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Objectives: The main goal of our research was to explore correlations between a history of uterine myomectomy and maternal-fetal outcomes, throughout a comparison between vaginal deliveries in patients with or without a history of uterine myoma excision. Materials and methods: A prospective study was carried out at two tertiary care hospitals between January 2019 and January 2020. Women were assigned into two groups according to the history of laparoscopic or laparotomic myomectomy (Group 1) or without myomectomy (Group 2). Results: 80 women successfully delivered after myomectomy. Pregnancies with previous laparoscopic or laparotomic myomectomy were associated with a minor rate of spontaneous labor onset (RR 1.17; 95% CI 1.04 − 1.31) and with an increased rate of emergency cesarean section (RR 1.22; 95% CI 1.09 − 1.36). Moreover, myomectomy group had a significant number of indications to emergency cesarean section correlated to suspected uterine rupture (RR 1.19; 95% CI 1.02–1.39). There were no uterine ruptures or neonatal deaths recorded. First stage of labor was longer in the myomectomy group (316 vs 204 mins, p = 0.01). No differences in the rates of the prolonged first and second stage of labor, postpartum hemorrhage and vaginal laceration, and no neonatal adverse outcomes were found between groups. Conclusions: Pregnancies after myomectomy might be associated with an elevated rate of emergency cesarean section only due to a higher percentage of suspected uterine rupture, without a real hazard of adverse obstetric or neonatal outcomes.

Background This paper describes the clinical practice and performance of cell-free DNA sequencing-based non-invasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population. Methods The AMES-accredited laboratory offers NIPT in maternal blood as a screening test for fetal T21, T18, T13 and SCA. Samples were sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay. Results A retrospective analysis was performed on 36,456 consecutive maternal blood samples, including 35,650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies. Samples were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. A result indicative of a classic trisomy was found in 356 (1%) of singleton or twin samples: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of a SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing. NIPT results were confirmed in 99.2% (247/249) of T21 cases, 91.2% (62/68) of T18 cases, 84.4% (27/32) of T13 cases, and 86.7% (117/135) of SCA cases. In the 35,955 cases reported as unaffected by a classic trisomy or SCA, no false negative cases were reported. Assuming that false negative results would be reported, the sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47–100.0), T18 (95% Cl 94.17–100.0), and T13 (95% Cl 87.54–100.0). The specificities were 99.99% (95% Cl 99.98–100.0), 99.98% (95% Cl 99.96–100.0), 99.99% (95% Cl 99.97–100.0), and 99.95% (95% Cl 99.92–99.97) for T21, T18, T13, and SCA, respectively. Conclusion This retrospective analysis of a large cohort of consecutive patients who had whole-genome sequencing-based NIPT for classic trisomies and SCA shows excellent detection rates and low false positive rates.

Background Inside-out transobturator tape (tension-free vaginal tape–obturator [TVT-O]) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence (SUI). However, data reporting long-term outcomes are lacking. Objective To assess the efficacy and safety of TVT-O 10 yr after implantation for the treatment of female pure SUI. Design, setting, and participants A multicenter, prospective study was conducted in five tertiary referral centers in three countries. All consecutive women with urodynamically proven pure SUI treated by TVT-O were included. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. Intervention TVT-O implantation. Outcome measurements and statistical analysis Data regarding subjective outcomes (International Consultation on Incontinence Questionnaire–Short Form, Patient Global Impression of Improvement, and patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Univariable analysis was performed to investigate outcomes. Results and limitations One hundred sixty-eight women had TVT-O implantation. At 10-yr follow-up, 160 patients (95%) were available for the evaluation. We did not find any significant change of the surgical outcomes during this time. At 10 yr after surgery, 155 of 160 patients (97%) declared themselves cured ( p =0.7). Similarly, at 10-yr evaluation, 148 of 160 patients (92%) were objectively cured. No significant deterioration of objective cure rates was observed over time ( p =0.4). The history of failure of previous anti-incontinence procedures (hazard ratio: 5.34; 95% CI, 2.61–11.9; p =0.009) was the only predictor of recurrence of SUI. The onset of de novo overactive bladder was reported by 23 of 160 patients (14%) at 10-yr follow-up. No other late complications were reported. Conclusions The 10-yr results of this study showed that TVT-O is a highly effective and safe option for the treatment of SUI. Patient summary At long-term follow up, tension-free vaginal tape-obturator is highly effective and safe for the treatment of stress urinary incontinence.

In this study, we investigated the role of the endovanilloid/endocannabinoid system in the glucocorticoid-induced osteoclast overactivity. Receptorial and enzymatic component of the endovanilloid/endocannabinoid system are expressed in bone cells, and dysregulated when bone mass is reduced. Moreover, blockade or desensitization of vanilloid receptor 1 (TRPV1) and/or stimulation of cannabinoid receptor 2 (CB2) are beneficial for reducing number and activity of the bone cells modulating resorption, the osteoclasts. We have treated in vitro healthy woman derived osteoclasts with methylprednisolone in presence or not of CB2 or TRPV1 agonists/antagonists, analysing the effect on osteoclast function and morphology through a multidisciplinary approach. Moreover, a treatment with a protein kinase C inhibitor to evaluate osteoclast activity and endovanilloid/endocannabinoid component expression levels was performed in osteoclasts derived from healthy subjects in presence of not of methylprednisolone. Our results show, for the first time, that the endovanilloid/endocannabinoid system is dysregulated by the treatment with methylprednisolone, that the osteoclast activity is increased and that pharmacological compounds stimulating CB2 or inhibiting TRPV1 might reduce, possible inhibiting protein kinase C beta II, the methylprednisolone-induced osteoclast over-activation, suggesting their therapeutic use for protecting from the glucocorticoid-induced bone mass loss.

BACKGROUND: Recent studies in literature, have raised some doubts on the routine use of urodynamic testing. Many physicians and articles recommend a selective use of this tool, considering carefully risks and benefits. These recommendations are intended to guide clinicians in the right selection of the male and neurological patients to submit to an urodynamic evaluation. This is the second part of a previous article regarding the urodynamic recommendations in the female population. METHODS: We reviewed the literature, regarding the use of UDS in male and neurological population with lower urinary tract symptoms (LUTS). Specifically, we analyzed and compared the guidelines and recommendations of the most important urology and uro-gynaecology international scientific societies. These publications were used to create the evidence basis for characterizing the recommendations to perform urodynamic testing. A panel of 10 experts was composed and Delphi process was followed to obtain the panelist consensus. The final recommendations were approved by the unanimous consensus of the panel and compared with the best practice recommendations available in the literature. RESULTS: The recommendations are provided for diagnosis and management of common LUTS in male and neurological population. CONCLUSIONS: This review provides a summary of the most effective utilization of urodynamic studies for the global evaluation of patients with lower urinary tract symptoms, and how to use them when really needed, avoiding unnecessary costs and patient inconveniences.

Perinatal depression (PD) is a severe and disabling condition impacting negatively on children in terms of adverse neonatal outcomes and on the well-being of women and their families. All pregnant women attending the unit of Gynecology and Obstetrics Service of the University of Campania "L. Vanvitelli" will be screened for PD using the Edinburgh Postpartum Depression Scale (EPDS). Women with a score ≥10 at the EPDS will be invited to receive a full psychiatric assessment. The required sample size is of 126 women with PD which will be randomly allocated to either an experimental group, receiving a uni-familiar psychoeducational intervention, or to a control group, receiving the Best Treatment Option (BTO). Patients will be evaluated through several assessment instruments: Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), Manchester Short Assessment of Quality of Life (MANSA), Family Assessment Device (FAD), Family Coping Questionnaire (FCQ), and Pattern of Care Schedule (PCS). Patients will be evaluated at baseline, 3, 6, 9, and 12 months post-randomization. The severity of depressive symptoms at the HAM-D scale has been selected as primary outcome. Other outcome measures include improvement in the severity of anxiety symptoms, of global and personal functioning, an improvement in family members' coping strategies and in the level of quality of life. It has been highlighted the importance of developing screening and treating programs for PD, and our study will use rigorous study design to evaluate the efficacy of the adaption of a well-known family psychoeducational model to the treatment of PD. The aims of present trial are to: (1) develop an informative package for pregnant women with PD; (2) promote a screening programme for PD; (3) identify those (socio-demographic and pregnancy-related environmental) factors associated with a higher risk to develop a perinatal or postnatal depression; (4) evaluate the efficacy of a new experimental psychoeducational intervention in reducing the depressive symptoms during pregnancy compared to the BTO.

AIM: The role of urodynamic study (UDS) in the management of female stress urinary incontinence (SUI) is one of the most controversial and debated topic in urogynecology. Here, we aimed to systematically assess the most relevant available evidence on urodynamics' value in the management of women with stress urinary incontinence. METHODS: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was performed in May 2018. Only randomized clinical trials, prospective studies, or retrospective studies articles evaluating the use of urodynamic studies in women with stress urinary incontinence were included. RESULTS: After screening a total of 3055 records, 39 studies published from 1996 to 2018 were included. CONCLUSIONS: In an uncomplicated population of women with SUI, it is not demonstrated that preoperative urodynamic evaluation can improve the outcome of continence surgery; however, UDS provides additional information regarding lower urinary tract function that could guide the physician to make the right therapeutic choice. UDS should be considered mandatory before surgery in complicated patients, but its use should also be evaluated in index patients when the results may help counseling and management of these women.

To investigate regarding the safety and effectiveness of a balloon catheter (Aqueduct-100 device) to dilate the uterine cervix before operative hysteroscopies. Secondary objectives were to evaluate the duration of the dilatation procedure and to investigate on physicians' satisfaction with the device.

Iron deficiency and particularly iron deficiency anemia (IDA) can lead to negative health consequences. This review describes the importance of adherence and persistence (adhering to treatment for the recommended duration) with iron replacement therapy in the prevention of complications, particularly regarding its recommended dosing schedule.Comprehensive literature searches were performed of Medline and the Cochrane library from 2000 to 2018. Keywords included iron deficiency or IDA, compliance or adherence, persistence, health beliefs, risk factor, complications, dosing cycles, oral iron replacement therapy and recommendations for duration, ferrous compounds, iron supplementation, dietary iron, and delayed-action/slow-release preparations.Identified articles focused on IDA as a risk factor (particularly for worsened comorbidities or surgical outcomes), guidelines, adherence and persistence, and differences between iron formulations. Current guidelines and expert opinion continue to support oral iron supplementation as first-line therapy. While it is recommended to take iron therapy for 2 months to normalize hemoglobin, then 2-3 months to build up iron stores, many patients face difficulties in adhering to and persisting with the full iron treatment regimen. Patient education and understanding, social support, simple dosing, perceived efficacy including reduced symptoms and tolerability were factors noted to promote medication adherence and persistence. Adherence to iron therapies appears to be facilitated by using ferrous sulfate due to its optimal absorption, and particularly extended-release forms due to their improved tolerability for iron deficiency.Proper adherence and persistence with iron supplementation may prevent or reduce the risk of complications of iron deficiency and IDA.

The effectiveness for vasomotor symptoms and sleep disorders plus the long-term safety of a nutraceutical combination of agnus-castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli were assessed in postmenopausal women. A controlled study was carried out in menopausal women comparing this nutraceutical combination (ESP group) with a formulation containing isoflavones alone (C group) at the dosage recommended. The Kuppermann index, The Pittsburgh Sleep Quality Index (PSQI), and Short Form 36 (SF-36) were determined at baseline, three, six and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. One hundred and eighty women were enrolled in the study (100 in the ESP group and 80 in the C group). At the end of the treatment, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. The Kuppermann index and particularly the tendency for hot flashes progressively and significantly decreased in frequency and severity during ESP versus C treatment. At the same time, a significant increase in sleep quality and psychophysical wellness parameters was observed in the ESP versus C groups. No adverse events were observed. Agnus-castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. The endometrium, mammary glands and liver function were unaffected after 12 months of treatment.

BACKGROUND: The aim of this study was to compare resectoscopic and small-diameter hysteroscopic techniques for endometrial polypectomy in patients with "unfavorable" cervix.METHODS: Eighty women with a single 2-4 cm sized endometrial polyp, with unfavorable cervical anatomical conditions were enrolled in the study. Forty patients were treated with a 26F resectoscope requiring cervical dilatation (group A), forty patients were treated with a 5-mm hysteroscope requiring vaginoscopic approach (group B). Operative time, fluid absorption, complications, instrument failure, postoperative pain, overnight stay were analyzed. Operative visualization, operative difficulty and overall surgeon's satisfaction were assessed with a Visual Analogue Scale (VAS).RESULTS: Operative time was significantly longer in group A than in group B (18.3 +/- 7.4 vs. 11.3 +/- 5.2 minutes), the cumulative complication rate and the need of postoperative analgesics were higher in group A than in group B. VAS of surgical difficulty and surgeon's satisfaction were higher in group B than in group A.CONCLUSIONS: The small-diameter hysteroscopy is a safe and effective approach for endometrial polyp up to 4 cm in patients with unfavorable cervical canal at risk of cervical injury. BACKGROUND: To compare resectoscopic and small-diameter hysteroscopic techniques for endometrial polypectomy in patients with "unfavorable" cervix. METHODS: Eighty women with a single 2-4 cm sized endometrial polyp, with unfavorable cervical anatomical conditions were enrolled in the study. Forty patients were treated with a 26F resectoscope requiring cervical dilatation (group A), forty patients were treated with a 5-mm hysteroscope requiring vaginoscopic approach (group B). Operative time, fluid absorption, complications, instrument failure, postoperative pain, overnight stay were analyzed. Operative visualization, operative difficulty and overall surgeon's satisfaction were assessed with a visual analogue scale. RESULTS: Operative time was significantly longer in group A than in group B (18.3±7.4 vs 11.3±5.2 minutes), the cumulative complication rate and the need of post-operative analgesics were higher in group A than in group B. Visual analogue scale of surgical difficulty and surgeon's satisfaction were higher in group B than in group A. CONCLUSIONS: The small-diameter hysteroscopy is a safe and effective approach for endometrial polyp up to 4 cm in patients with unfavorable cervical canal at risk of cervical injury.

Surgery represents the mainstay of treatment for pelvic organ prolapse (POP). Among different surgical procedures, abdominal sacrocolpopexy (SC) is the gold standard for apical or multicompartmental POP. Research has recently focused on the role of robot-assisted sacrocolpopexy (RASC).To conduct a systematic review on the outcomes of RASC.PubMed, Scopus, and Web of Science databases as well as ClinicalTrials.gov were searched for English-language literature on RASC. A total of 509 articles were screened; 50 (10%) were selected, and 27 (5%) were included. Studies were evaluated per the Grading of Recommendations, Assessment, Development, and Evaluation system and the European Association of Urology guidelines.Overall, data on 1488 RASCs were collected from 27 studies, published from 2006 to 2013. Objective and subjective cures ranged from 84% to 100% and from 92% to 95%, respectively. Conversion rate to open surgery was1% (range: 0-5%). Intraoperative, severe postoperative complications, and mesh erosion rates were 3% (range: 0-19%), 2% (range: 0-8%), and 2% (range: 0-8%), respectively. Surgical-related outcomes have improved with increased experience, with an estimated learning curve of about 10-20 procedures. Laparoscopic SC is less costly than RASC, although the latter has lower costs than abdominal SC.RASC is a safe and feasible procedure for POP; it allows the execution of complex surgical steps via minimally invasive surgery without medium- and long-term anatomic detriments. Further prospective studies are needed to confirm these findings.We looked at the outcomes of robotic sacrocolpopexy for prolapse. We found that the use of robotic technology is safe and effective for the treatment of prolapse in women.

Studies have observed a significant heterogeneity in efficacy data for single-incision minislings (SIMS) as surgical treatment for female urinary incontinence (UI). Our study aim was to test the hypothesis that different vaginal kits for SIMS have different long-term outcomes. One hundred and twenty women with stress (SUI) or mixed (MUI) UI were enrolled in a multicenter randomized clinical trial (registration number NCT00751088) and treated with three different SIMS (Ajust®, MiniArc®, or TVT Secur System®). Duration of follow-up was at least 24 months from surgery. The primary outcome was the subjective cure rate at 24 months from surgery; secondary outcomes were rates of total failure and reoperations for UI. At study end, no difference was detected between groups in terms of total subjective cure rate [21 (52.5 %) vs. 26 (65.0 %) vs. 21 (52.5 %), in Ajust®, MiniArc®, and TVT Secur System® group, respectively; P = 0.412] or in terms of total failure rate [24 (60.0 %) vs. 22 (55.0 %) vs. 27 (67.5 %), in Ajust®, MiniArc®, and TVT Secur System® group, respectively; P = 0.432]. The proportion of patients who received a second surgery for UI was also not significantly different between groups [13 (32.5 %) vs. 10 (25.0 %) vs. 13 (32.5 %), in Ajust®, MiniArc®, and TVT Secur System®, respectively; P = 0.831]. The long-term efficacy of SIMS does not differ between the vaginal kits examined.

Uterine tumors with sex-cord-like differentiation are extremely rare types of uterine stromal neoplasm. These tumors were classified into two groups with considerable practical relevance because clinical behaviour of uterine tumor resembling ovarian sex cord tumor (UTROSCT) differs widely from its closely related endometrial stromal tumors with sex-cord-like elements (ESTSCLE). Treatment and prognosis of these tumors are unresolved issues because of the exiguous number of reported cases. We describe a rare case of endometrial stromal tumor with sex-cord-like differentiation successfully treated by resectoscopic surgery and conservation of the uterus, in an infertile patient affected by metrorrhagia. This procedure resulted in a pregnancy immediately after treatment and in a successful delivery. During 60 months of follow-up no evidence of recurrence was observed.

Objective To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. Study design This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with

The aim of the study was to determine, using perineal ultrasound, the physiological range for urethral mobility in normal women. Sixty healthy women were enrolled. The ultrasound parameters obtained with a perineal "static" and "dynamic" evaluation method were: pubic-urethral distance and inclination angle of the urethral axis. We propose a physiological range of pubic-urethral distance under stress in young women between 10 and 15 mm, the inclination angle of the urethral axis is between 60 and 100 degrees . In peri-post-menopause women we establish a non-rigid range of mobility in relation to age and parity: between 15 and 18 mm for the pubis-urethra distance and 80 degrees and 120 degrees for the angle of the urethral axis. Defining a range of normality for urethral mobility through ultrasound is useful for further studying therapeutic choices and help to identify the surgical correction and post-operative follow-up.

Objective: To investigate the effect of raloxifene on atherosclerosis progression in healthy postmenopausal women. Design: In a prospective fashion, a total of 155 healthy postmenopausal women were randomly assigned to receive raloxifene 60 mg/day or a matching placebo for 18 months. Atherosclerosis progression was evaluated by B-mode ultrasonography measuring the intima-media thickness (IMT) of the carotid arteries. Plasma levels of triglycerides, low-density lipoprotein cholesterol, soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, E-selectin, interleukin-6, tumor necrosis factor a, adiponectin, and the degree of insulin resistance by the homeostatic model assessment method were also determined. Results: The progression slope of carotid IMT was 0.0112 mm/18 months in the raloxifene group and 0.0857 mm/18 months in the placebo group (P < 0.004). Raloxifene treatment compared with placebo produced a significant decrease in plasma triglycerides (P < 0.02), low-density lipoprotein cholesterol (P < 0.02), soluble forms of intercellular adhesion molecule-1(P < 0.005) and vascular cell adhesion molecule-1 (P < 0.04), E-selectin (P < 0.02), interleukin-6 (P < 0.005), tumor necrosis factor a (P < 0.005) levels, and homeostatic model assessment index (P < 0.005) and a significant increase in plasma adiponectin levels (P < 0.001). Logistic regression analysis indicated that women receiving raloxifene had a lower risk of IMT progression (odds ratio = 0.41; 95% CI: 0.32-0.70). Conclusion: Raloxifene treatment, possibly through an increase in plasma adiponectin levels, may slow the progression of IMT in postmenopausal women.

Background The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement. Aim In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls. Methods We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay. Results In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1-3.4; p = 0.02) of presenting with an early menarche (age at menarche

Objective Human papillomavirus (HPV) has been recognized as the major etiologic agent of cervical squamous cell carcinoma. However, it has been demonstrated that HPV infection is usually a self-limited process and does not lead to significant epithelial lesions or cancer. Recent data indicate that persistent high-risk HPV (HR-HPV) infections have a significantly increased risk of developing incident high-grade cervical intraepithelial neoplasia and cervical cancer. Our aim, therefore, was to assess whether there exist HPV genotypes whose persistence can be considered powerful surrogates of a progressive disease. We retrospectively selected all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance, with a positive test for HR-HPV, different from HPV types 16 and 18, and assessed the significance of the risk of progression based on the persistence of the specific HR-HPV. Materials and methods We retrospectively queried the database of our Colposcopy Clinic for all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance and a positive test for HR-HPV, and we calculated the incidence of progression to lesions greater than or equal to low-grade squamous intraepithelial lesions after 6 months, according to the HPV type. Results A progression rate of 48.27% was found in patients tested positive for HPV-31 (Group 1), 38.46% in patients tested positive for HPV-45 (Group 2), and 5.73% in patients tested positive for HPV types other than HPV-16, HPV-18, HPV-31, and HPV-45 (Group 3). Conclusion Our data demonstrate that the persistence of HPV-31 and HPV-45 is strongly associated with the occurrence of squamous intraepithelial lesion.

The authors report a case of a 61-year-old woman diagnosed with large bladder diverticulum. Diagnosis was performed only after a series of investigations carried out for the occasional finding of hypercreatininaemia. Although the significant volumes of post void residual (PVR) and the relevant urine stagnation in the diverticulum, subjective symptomatology was absent and urinalysis and urine culture were negative. The scheduled therapeutic plan consisted of fosfomycin three grams every ten days for sixmonths, self-catheterization twice a day, voiding on a time schedule, and adequate fluid intake. The monthly scheduled follow-up at one year showed good general health, good compliance with the therapy, no urinary tract infections, a decrease in creatininemia to 1.2 mg/dl, and regression of nephrohydrosis to a mild stage. In conclusion, the absence of symptoms and negative urinalysis or urine culture allows expectant management despite the considerable size of the bladder diverticulum.

Introduction: Over the past 30 years, gonadotropin-releasing hormone agonists (GnRH-a) have been used to induce a hypoestrogenic status in women with endometriosis with the aim to cause an improvement in pain symptoms similar to that observed after menopause. Triptorelin is one of the most commonly used GnRH-a. Areas covered: This review offers an explanation of the mechanism of action, of the pharmacokinetics and pharmacodynamics of triptorelin and gives the readers a complete overview of the studies on the clinical efficacy, tolerability and safety of this agent in patients with endometriosis. Expert opinion: The studies reviewed in the current manuscript demonstrate the efficacy of triptorelin in improving pain symptoms caused by endometriosis. Further, this effect is confirmed by the reduction in the volume of the endometriotic nodules during treatment. Future research should evaluate whether the pre-operative administration of triptorelin prior to surgical excision of endometriomas may be useful in p...

INTRODUCTION: We assess the effectiveness of intravesical instillation of hyaluronic acid (HA) and chondroitin sulphate (CS) as a non-antibiotic treatment option for prophylaxis of recurrent urinary tract infections (UTIs) in female patients. METHODS: This was a retrospective cohort study involving 7 European institutions. We included patients with recurrent UTIs who received intravesical instillations of Ialuril (IBSA International) (50 mL HA 1.6% and CS 2% solution) between January 2010 and March 2012. Medication schedule, length of follow-up, recurrence infection time, number of UTIs/patients/year, patient quality of life, subjective symptoms score, and treatment-emergent side effects were recorded and analyzed. RESULTS: In total, 157 women (mean age: 54.2 ± 4.1 years) were included in the analysis. All patients had at least 12 months follow-up. After 4 weekly and 5 monthly HA-CS bladder instillations, UTI episodes decreased from 4.13 ± 1.14 to 0.44 ± 0.50 (p = 0.01) at 12 months, while recurrent UTI time prolonged from 94.8 ± 25.1 days to 178.4 ± 37.3 days (p = 0.01) at 12 months. An improvement in symptoms and quality of life was achieved. A medium-depth pain after medication instillation was the most reported side effect. Regression model analysis showed significant risk factors in developing new UTI episodes: being more than 50 years old and having more than 4 UTI episodes per year (OR 3.41; CI 95%; 1.51-7.71, p = 0.003 and OR 3.31; CI 95% 1.51-7.22; p = 0.003, respectively). Retrospective design and lack of a control group represent two main limitations of the study. CONCLUSIONS: Restoring glycosaminoglycans bladder layer therapy is a promising non-antibiotic therapy to prevent recurrent UTIs Introduction: We assess the effectiveness of intravesical instillation of hyaluronic acid (HA) and chondroitin sulphate (CS) as a non-antibiotic treatment option for prophylaxis of recurrent urinary tract infections (UTIs) in female patients.Methods: This was a retrospective cohort study involving 7 European institutions. We included patients with recurrent UTIs who received intravesical instillations of Ialuril (IBSA International) (50 mL HA 1.6% and CS 2% solution) between January 2010 and March 2012. Medication schedule, length of follow-up, recurrence infection time, number of UTIs/patients/year, patient quality of life, subjective symptoms score, and treatment-emergent side effects were recorded and analyzed.Results: In total, 157 women (mean age: 54.2 ± 4.1 years) were included in the analysis. All patients had at least 12 months followup. After 4 weekly and 5 monthly HA-CS bladder instillations, UTI episodes decreased from 4.13 ± 1.14 to 0.44 ± 0.50 (p = 0.01) at 12 months, while recurrent UTI time prolonged from 94.8 ± 25.1 days to 178.4 ± 37.3 days (p = 0.01) at 12 months. An improvement in symptoms and quality of life was achieved. A medium-depth pain after medication instillation was the most reported side effect. Regression model analysis showed significant risk factors in developing new UTI episodes: being more than 50 years old and having more than 4 UTI episodes per year (OR 3.41; CI 95%; 1.51-7.71, p = 0.003 and OR 3.31; CI 95% 1.51-7.22; p = 0.003, respectively). Retrospective design and lack of a control group represent two main limitations of the study.Conclusions: Restoring glycosaminoglycans bladder layer therapy is a promising non-antibiotic therapy to prevent recurrent UTIs.

To compare single-incision mini-slings (SIMSs) and retropubic tension-free vaginal tape (r-TVT) in terms of the long-term efficacy and safety for the treatment of female stress (SUI) or mixed urinary incontinence (MUI).Prospective multicenter cohort trial (registration number NCT00751088) (Canadian Task Force II).Department of Obstetrics and Gynecology, Italy.Two hundred-forty women with SUI/MUI.SIMS or r-TVT.The operative time and the use of analgesic tablets were significantly (p.001) higher and lower, respectively, in the r-TVT group versus the SIMS group. After 24 months of follow-up, no difference between the study arms was observed in terms of the complication rate (30/120 [25%] vs 19/120 [15.8%] for the r-TVT and SIMS arms, respectively; relative risk = 1.58; 95% confidence interval, 0.94-2.65; p = .083), whereas the subjective cure rate was significantly lower in the SIMS arm than in the r-TVT arm (57/103 [55.3%] vs 89/106 [84.0%] for the r-TVT and SIMS arms, respectively; relative risk = 0.66; 95% confidence interval, 0.54-0.80]; p.001). The proportion of retreated patients for SUI/MUI was significantly higher in the SIMS arm than in the r-TVT arm (37/103 [34.9%] vs 12/106 [11.3%] for SIMS and r-TVT arm, respectively; p.001).SIMS has no advantage in terms of safety over r-TVT and was found to be less effective than r-TVT. Thus, its use in the clinical practice should be questioned.

Approximately 20–30 % of women suffer from recurrent cystitis. Recently, the problem of bacterial internalization, especially by Escherichia coli, has been significantly emerging as the main cause of recurrent episodes. It is believed that such a process is favored by damage to the urothelial mucous membrane. Concerning this, intravesical therapy with hyaluronic acid alone or in association with chondroitin sulfate was shown to improve urothelium thickness and reduction of bacterial load in the urine. The aim of our study was to assess whether intravesical therapy with hyaluronic acid (HA) and chondroitin sulfate (CS) is more effective than antibiotic therapy in reducing episodes and symptoms of recurrent urinary tract infections. We compared the number of recurring episodes in three groups of patients affected by recurrent urinary tract infections assigned to three different therapeutic regimens: the first group was treated only with HA and CS, the second group with HA and CS associated with fosfomycin, and the third group was treated only with fosfomycin (F). We assessed the number of recurrent episodes for each patient that occurred during a 6- to 12-month follow-up. The results showed 72.7 % of patients in the HA-CS group, 75 % in the fosfomycin + HA-CS group, and only 30.4 % in the fosfomycin group were event free at follow-up. The results were analyzed using the Fisher’s exact test. In conclusion, intravesical therapy with hyaluronic acid and chondroitin sulfate is an effective therapeutic approach to treat and prevent episodes of recurrent cystitis.

Background Inside-out tension-free vaginal transobturator tape (TVT-O) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence (SUI), but data reporting long-term outcomes are scarce. Objective To evaluate the efficacy and safety of TVT-O 5-yr implantation for management of pure SUI in women. Design, setting, and participants A prospective observational study was conducted in four tertiary reference centers. Consecutive women presenting with urodynamically proven, pure SUI treated by TVT-O were included. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. Intervention TVT-O implantation without any associated procedure. Outcome measurements and statistical analysis Data regarding subjective outcomes (International Consultation on Incontinence-Short Form [ICIQ-SF], Patient Global Impression of Improvement, patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Multivariable analyses were performed to investigate outcomes. Results and limitations Of the 191 women included, 21 (11.0%) had previously undergone a failed anti-incontinence surgical procedure. Six (3.1%) patients were lost to follow-up. The 5-yr subjective and objective cure rates were 90.3% and 90.8%, respectively. De novo overactive bladder (OAB) was reported by 24.3% of patients at 5-yr follow-up. Median ICIQ-SF score significantly improved from 17 (interquartile range [IQR]:16–17) preoperatively to 0 (IQR: 0–2) ( p Failure of a previous anti-incontinence procedure was the only independent predictor of subjective recurrence of SUI (hazard ratio [HR]: 4.4; p =0.009) or objective (HR: 3.7; p =0.02). No predictive factor of de novo OAB was identified. Conclusions TVT-O implantation is a highly effective option for the treatment of women with pure SUI, showing a very high cure rate and a low incidence of complications after 5-yr follow-up.

Bone is a highly metabolically active tissue and its formation and resorption is at the base of bone remodelling. The critical importance of a balanced bone remodelling is demonstrated by human diseases, i.e. osteoporosis, in which a net increase in bone resorption is responsible of skeleton weakening and fracture risk. Oestrogens display anti-resorptive properties on bone metabolism. Indeed, the so-called post-menopausal osteoporosis occurs after interruption of gonad function and benefits from hormonal replacement treatment. Recently, an important role for the endocannabinoid system in the regulation of skeletal remodelling in human has also been shown. In particular, we showed that CB2 stimulation is able to reduce the number of human OCs in vitro. Here, we provide unprecedented evidence that 17-β-oestradiol administration inhibits activity and formation of human OCs in vitro, demonstrating that oestrogens are able to induce an increase of CB2 expression probably through the recruitment of a putative oestrogens responsive element in the CB2 encoding for gene. © 2012 Elsevier Ltd.

Background: One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings. Objective: To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up. Design, setting, and participants: This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. Intervention: Standard retropubic TVT. Measurements: Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes. Results and limitations: A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p > 0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9 cm H2O (hazard ratio [HR]: 16.2; p = 0.01) and maximum detrusor pressure during the voiding phase

Single-incision mini-slings (SIMS) are new minimally invasive devices used for female stress urinary incontinence (SUI). To date, several SIMS are available, but few and uncontrolled comparative data have assessed their safety and feasibility. The aim of the present clinical study was to compare three different SIMS in an ambulatory setting.One hundred and twenty patients with SUI were randomized to receive three SIMS: Ajust, MiniArc, and TVT Secur System. Surgical data were compared.Significantly (P0.05) lower surgical difficulty and higher patient satisfaction were detected in the MiniArc group when compared to the Ajust and TVT Secur System groups. A significantly (P0.05) higher feasibility under local anesthesia and in ambulatory setting was also detected for the MiniArc group. The overall complication rate was significantly (P0.05) lower in the MiniArc group than in the TVT Secur System group.MiniArc is simpler to insert under local anesthesia and in an ambulatory setting. It is safer than the TVT Secur System, and is related to higher patient satisfaction.

Human osteoclasts express functional TRPV1 channels, CB1/CB2 cannabinoid receptors and endocannabinoid/endovanilloid synthetic/catabolic enzymes. Pharmacologic manipulation of this system can modulate osteoclast activity. Here, through multidisciplinary approaches, we demonstrate that enzymes and receptors of the endocannabinoid/endovanilloid system are differently expressed in osteoclasts from menopausal women without or with osteoporosis. We report that in osteoclasts from osteoporotic patients, TRPV1 channels are upregulated and, if persistently stimulated with resiniferatoxin, become clustered to the plasma membrane while inducing a massive over-expression of CB2 receptors. By providing new evidence for a critical functional cross-talk between CB2 and TRPV1 receptors in osteoporosis, we speculate that TRPV1 desensitization, or its enhanced trafficking, together with TRPV1 agonist-induced CB2 receptor overexpression, might be critical to minimize calcium entry in osteoclasts, which could be in turn responsible of cell over-activation and higher bone resorption. Our data pave the way to the use of TRPV1 agonist together with CB2 agonists or CB1 antagonists in osteoporosis. © 2011.

Aim of our study was to evaluate the effectiveness of the association between N-Palmitoylethanolamine and transpolydatin in the management of chronic pelvic pain related to EMS.This was a randomized, double-blind, parallel-group, placebo-controlled clinical trial involving 61 subjects, submitted to a first line laparoscopic conservative surgery, who were randomized into 3 groups receiving: group A (n=21) the association N-Palmitoylethanolamine-transpolydatin 400 mg + 40 mg twice a day for 3 months; group B (n=20) the placebo for 3 months; group C (n=20) a single course of Celecoxib 200mg twice a day for 7 consecutive days. Assessments of the severity of pelvic endometriosis (pelvic pain, dysmenorrhoea and dyspareunia) were recorded before and after treatment on a questionnaire and a 10-point VAS. Differences between groups were verified with Kruskal-Wallis ANOVA for non-parametric multiple comparisons.A marked decrease in dysmenorrhoea, dyspareunia and pelvic pain was observed in all groups, and the association between N-Palmitoylethanolamine and transpolydatin resulted to be more effective than placebo (P.001). Additionally, the treatment with Celecoxib resulted in a decrease in pelvic pain more effective either than the association N-Palmitoylethanolamine and transpolydatin or placebo.These preliminary results show that the association between micronized N-Palmitoylethanolamine and transpolydatin is effective in the management of pelvic pain related to endometriosis after laparoscopy. Additionally, this association seems to be safe, shows an optimal control of pain and can be used in patients who are unable to receive other therapies.

The aim of the present study was to assess the relationship between lower urinary tract symptoms, anatomical findings, and baseline characteristics in women with pelvic organ prolapse (POP). A cross-sectional observational study was performed, enrolling consecutive women seeking cares for lower urinary tract symptoms (LUTS) with evidence of POP. Data regarding baseline characteristics, LUTS, and physical examination were gathered for each patient. Multivariate analysis (multiple linear regression (MLR)) and artificial neural networks (ANNs) were performed to design predicting models. A total of 1,344 women were included. Age, BMI, pelvic organ prolapse quantification (POP-Q) stage I, and previous surgery for urinary incontinence resulted predictors of urgency and stress incontinence. POP-Q stages III–IV were related to voiding dysfunction and POP symptoms. Age, BMI, and menopausal status resulted predictors for sexual dysfunction. Receiver operating characteristic comparison confirmed that ANNs were more accurate than MLRs in identifying predictors of LUTS. LUTS result from a fine interaction between baseline characteristics and anatomical findings. ANNs are valuable instrument for better understanding complex biological models.

Objective To evaluate the effects of low-dose hormone therapy (LD-HT) on bleeding pattern and vasomotor symptoms in perimenopausal women. Methods In a prospective, open-label study at an University clinic, 120 perimenopausal women suffering from irregular menstrual cycles and hot flushes were randomized to micronized 17β-estradiol 1 mg plus dydrogesterone 10 mg sequential added (LD-HT; group A: 60 subjects) or dydrogesterone 10 mg from day 15 to 28 (group B: 60 subjects). Number and severity of hot flushes and bleeding pattern were assessed throughout the study. Results Women in group A experienced a significant reduction in number of hot flushes while no significant variation was observed in group B. The incidence of cyclic bleeding was 86% in group A and 76% in group B, the mean duration was significantly lower in group A than in group B. Conclusions LD-HT may control both irregular bleeding and hot flushes in perimenopausal women.

Notch proteins are a transmembrane receptor family that is structurally and functionally conserved from worms to humans. The mammalian family of Notch proteins consists of several genes encoding Notch receptors and related Notch ligands. Notch signaling is involved in different aspects of the cell-fate decision tree: differentiation, proliferation, and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and correct fetal growth. Notch and its ligands also participate in vascular remodeling and stabilization. Vasculogenesis and blood regulation are of importance in the human placenta for normal fetal development and growth; any disorder of these systems leads to preeclampsia. Drawing on this background, we have investigated the expression of Notch-1, Notch-4, and Jagged-1, together with two members related to the Notch pathway in angiogenesis: VEGF and p21. Normal and preeclamptic human placentas have been evaluated by immunohistochemistry. In preeclamptic samples, a down-regulation of Notch pathway members occurs with a weak/moderate expression of the Notch protein members in all components of placenta compared with physiological placentas that, at term, exhibit the strong expression of Jagged-1 and a moderate expression of both Notch-1 and Notch-4 in all compartments of the placental villi. Moreover, preeclamptic samples also reveal a down-regulation of VEGF expression, together with a moderate nuclear expression of p21(Cip1) in the syncytiotrophoblast, cytotrophoblast, and endothelial cells. This down-regulation of VEGF in preeclamptic placentas, in turn, probably decreases Notch protein expression in placental compartments and in endothelial cells and could offer an ethiopathogenetic explanation for the onset of this pathology.

Objectives Connective tissue consists of fibroblasts and extracellular matrix (ECM) with collagen and elastic fibers, glycoproteins and proteoglycans (PGs) and it is considered an important factor of the supportive structures of the genitourinary region. Since PGs are essential for the organization of the collagen fibrils in the ECM, we investigated the presence of two PGs, fibromodulin and lumican, and of collagen type I in the periurethral connective tissue from women with stress urinary incontinence (SUI), compared to asymptomatic controls. Methods Thirty-two patients participated in the study and they were divided into four groups: premenopausal incontinents, premenopausal controls, postmenopausal incontinents and postmenopausal controls. All patients underwent gynaecologic surgical procedures and punch biopsies from the periurethral tissue were obtained. Immunohistochemistry for collagen type I, fibromodulin and lumican was performed on the histological slides. Results In premenopausal incontinents the immunoreactivity for collagen type I was weaker with an irregular distribution compared to premenopausal controls; while for fibromodulin, the staining was stronger in premenopausal incontinents than in premenopausal controls. Between the two postmenopausal groups there was not a significant difference in the intensity of collagen type I and fibromodulin staining that instead were less strong than in premenopausal groups. Lumican staining had the same distribution in the four groups. Conclusions Our results suggest an altered remodelling of connective tissue in the periurethral region of premenopausal patients with SUI, with a significant decrease of collagen content and an irregular organization and distribution of the collagen fibrils, compared to premenopausal controls. In the SUI patients this abnormal ECM remodelling, mainly related to the observed change in PGs expression, might affect significantly the tensile strength of the connective tissue and consequently the support that is provided by the urogenital suspensory apparatus to urethra and bladder base. Moreover, the significant decrease in collagen type I content in postmenopausal patients respect to premenopausal patients, suggests that age and hormonal factors could contribute to the pathological modifications of the supportive genitourinary connective tissues in the SUI patients.

Background: According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg. Objectives and Methods: The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-β-cyclodextrin (HPβCD) and progesterone/HPβCD associations. Results: The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPβCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPβCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the new formulation of progesterone was shown to be safe and not inferior to other products already on the market, with the exception of progesterone administered vaginally. Conclusions: As shown by the results of clinical studies presented in this review, the newly approved medicines containing cyclodextrins have been found to be as effective and as well-tolerated as other medicinal products that do not contain cyclodextrins. Moreover, the newly approved lower dose of diclofenac associated with cyclodextrins is consistent with the European Medicines Agency recommendations reported in the revision of the Assessment Report for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Cardiovascular Risk. Finally, the use of cyclodextrins led to significant increases in solubility and bioavailability of drugs, such as diclofenac and progesterone, and improvement in the efficacy and safety of these drugs.