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BACKGROUND Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis. METHODS We are conducting an ongoing phase 3 trial involving adults with biopsy-confirmed NASH and a fibrosis stage of FIB, F2, or F3 (stages range from FO [no fibrosis] to F4 [cirrhosis]). Patients were randomly assigned in a 1:1:1 ratio to receive once-daily resmetirom at a dose of 80 mg or 100 mg or placebo. The two primary end points at week 52 were NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by >2 points; scores range from 0 to 8, with higher scores indicating more severe disease) with no worsening of fibrosis, and an improvement (reduction) in fibrosis by at least one stage with no worsening of the NAFLD activity score. RESULTS Overall, 966 patients formed the primary analysis population (322 in the 80-mg resmetirom group, 323 in the 100-mg resmetirom group, and 321 in the placebo group). NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100-mg resmetirom group, as compared with 9.7% of those in the placebo group (P<0.001 for both comparisons with placebo). Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group, as compared with 14.2% of those in the placebo group (PcO.OOl for both comparisons with placebo). The change in low-density lipoprotein cholesterol levels from baseline to week 24 was -13.6% in the 80-mg resmetirom group and -16.3% in the 100-mg resmetirom group, as compared with 0.1% in the placebo group (PcO.OOl for both comparisons with placebo). Diarrhea and nausea were more frequent with resmetirom than with placebo. The incidence of serious adverse events was similar across trial groups: 10.9% in the 80-mg resmetirom group, 12.7% in the 100-mg resmetirom group, and 11.5% in the placebo group. CONCLUSIONS Both the 80-mg dose and the 100-mg dose of resmetirom were superior to placebo with respect to NASH resolution and improvement in liver fibrosis by at least one stage. (Funded by Madrigal Pharmaceuticals; MAESTRO-NASH ClinicaITrials.gov number, NCT03900429.). [ABSTRACT FROM AUTHOR]

Background and Aims: Resmetirom, liver-directed thyroid-hormone receptor-β agonist, received approval for metabolic dysfunction-associated steatohepatitis (MASH) treatment. We assessed health-related quality of life (HRQL) in patients with MASH treated with resmetirom., Approach and Results: Patients with MASH/NASH without cirrhosis and with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled phase III clinical trial with serial biopsy assessments at baseline and week 52 (MAESTRO-NASH, NCT03900429). HRQL was assessed using Chronic Liver Disease Questionnaire-NASH (CLDQ-NAFLD) and Liver Disease Quality of Life (LDQOL). Baseline HRQL score changes by treatment group (resmetirom 80 mg, resmetirom 100 mg, or placebo) and histological response (improvement of fibrosis without worsening of NAS or resolution of MASH/NASH without worsening of fibrosis) were compared after 52 weeks. Included were 966 intention-to-treat patients: 323 received resmetirom 100 mg, 322 resmetirom 80 mg, and 321 placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQL improvement in CLDQ-NAFLD Worry domain (mean +0.21 to +0.24, p < 0.05). At week 52, subjects who met histologic endpoints after treatment with resmetirom (100 mg and 80 mg pooled) experienced HRQL improvement in CLDQ-NAFLD Worry +0.46 (41% met minimal clinically important difference [MCID]), LDQOL domains: Role Emotional +3.0 (28% met MCID), Health Distress +8.1 (38% MCID), Stigma +3.5 (39% MCID), and total LDQOL +2.2 (35% MCID) (all p < 0.05). Similar improvements were noted in histologic responders from 100 mg or 80 mg resmetirom groups when separated-no improvements in placebo or nonresponders. Baseline F3 histologic responders had similar/more pronounced HRQL improvements., Conclusions: Patients with MASH/NASH with fibrosis improvement or the resolution of MASH with resmetirom experienced clinically meaningful and statistically significant HRQL improvements., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. MAESTRO-NAFLD-1 was a 52-week randomized, double-blind, placebo-controlled phase 3 trial evaluating the safety of resmetirom in adults with nonalcoholic fatty liver disease and presumed NASH. Patients were randomized to three double-blind arms (100 mg resmetirom (n = 325), 80 mg resmetirom (n = 327) or placebo (n = 320)) or open-label 100 mg resmetirom (n = 171). The primary end point was incidence of treatment-emergent adverse events (TEAEs) over 52 weeks and key secondary end points were LDL-C, apoB, triglycerides (over 24 weeks), hepatic fat (over 16 and 52 weeks) and liver stiffness (over 52 weeks). Resmetirom was safe and well tolerated. TEAEs occurred in 86.5% (open-label 100 mg resmetirom), 86.1% (100 mg resmetirom), 88.4% (80 mg resmetirom) and 81.8% (placebo) of patients. TEAEs in excess of placebo included diarrhea and nausea at the initiation of treatment. Key secondary end points included least square means difference from placebo at 80 mg, 100 mg resmetirom: LDL-C (-11.1%, -12.6%), apoB (-15.6%, -18.0%), triglycerides (-15.4%, -20.4%), 16-week hepatic fat (-34.9%, -38.6%), (P < 0.0001) and liver stiffness (-1.02, -1.70) and 52-week hepatic fat (-28.8, -33.9). These findings demonstrate resmetirom was safe and well tolerated in adults with presumed NASH, supporting a role for further clinical development. (ClinicalTrials.gov identifier NCT04197479 )., (© 2023. The Author(s).)

Background and Objectives : Since the Food and Drug Administration's (FDA) approval in 2005, the application of robotic surgery (RS) in gynecology has been adopted all over the world. This study aimed to provide an update on RS in benign gynecological pathology by reporting the scientific recommendations and high-value scientific literature available to date. Materials and Methods: A systematic review of the literature was performed. Prospective randomized clinical trials (RCT) and large retrospective trials were included in the present review. Results: Twenty-two studies were considered eligible for the review: eight studies regarding robotic myomectomy, five studies on robotic hysterectomy, five studies about RS in endometriosis treatment, and four studies on robotic pelvic organ prolapse (POP) treatment. Overall, 12 RCT and 10 retrospective studies were included in the analysis. In total 269,728 patients were enrolled, 1721 in the myomectomy group, 265,100 in the hysterectomy group, 1527 in the endometriosis surgical treatment group, and 1380 patients received treatment for POP. Conclusions: Currently, a minimally invasive approach is suggested in benign gynecological pathologies. According to the available evidence, RS has comparable clinical outcomes compared to laparoscopy (LPS). RS allowed a growing number of patients to gain access to MIS and benefit from a minimally invasive treatment, due to a flattened learning curve and enhanced dexterity and visualization.

Objective: This study aimed to analyze the effects of a six-month therapy with ulipristal acetate (UPA) on myoma size and endometrial thickness in premenopausal women., Material and Methods: Seventy-four women undergoing conservative therapy with UPA were enrolled for this study. All women underwent transvaginal ultrasound evaluation to assess the endometrial thickness, and the number and size of myomas at the beginning and after six months. Hysteroscopy and biopsy were performed after six months, if necessary., Results: After six months of treatment, sonographic examination showed a statistically significant ( p  < .05) reduction of the size of the largest myoma (56.3 ± 5.1 vs. 31.7 ± 10.1 mm) and a statistically significant ( p  < .05) increase in endometrial thickness (5.9 ± 2.1 vs. 9.7 ± 3.4 mm). Twenty-two patients with endometrial thickness >10 mm or nonhomogeneous pattern and ten patients with metrorrhagia underwent hysteroscopy: the most frequent finding was the combination of endometrial hypotrophy, floating surface, and chicken-wire vascular pattern aspect (14 cases, 43.7%). Histologic findings showed no case of complex hyperplasia., Conclusion: UPA is a safe, effective and assured method to decrease symptoms, reduce the need for surgery in premenopausal women suitable for the treatment.

Background: Endocannabinoids/endovanilloid (EC/EV) system and inflammation are recognized as key regulators of cell-signaling pathways in female reproduction. The knowledge of predictive biomarkers involved in preterm birth (PTB) represents an important goal to make an early diagnosis. The aim of the study was to investigate the role of EC/EV system and inflammation in human delivery, in placental samples from spontaneous deliveries., Methods: We examined the expression of genes encoding for the components of EC/EV system (CB1, CB2, TRPV1, MAGL, FAAH, DAGL, NAPE-PLD) and for inflammatory cytokines (IL-6, TNF-α) with qRT-PCR techniques, in human placental samples from preterm delivery (at 30 and at 34 weeks) compared to term delivery (40 weeks, control group)., Results: We found a marked increase of CB1, anandamide, and inflammatory cytokines, mainly TNF-α, together with TRPV1 down-regulation in term delivery group, compared to preterm groups (P<0.05)., Conclusions: Our findings highlighted the emergent pivotal role of the EC/EV system and inflammation in spontaneous term delivery and provided the framework for future studies that investigate the CB1/TRPV1 crosstalk in preterm birth. Particularly, we found a link between the stimulation of CB1 receptors and the antagonism of TRPV1 channels, that could be used in PTB prevention, through selected molecules.

Background and Objectives: Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of vasomotor hot flushes and night sleep disturbances in postmenopausal women. Materials and Methods: We performed an electronic search from the beginning of all databases to July 2019. All results were then limited to a randomized trial. Restrictions for language or geographic location were not utilized. Inclusion criteria were randomized clinical trials of physiological or surgical postmenopausal women experiencing hot flushes and sleep disturbances who were randomized to either low-dose paroxetine or placebo (i.e., formulations without active ingredients). The primary outcome evaluated was the mean weekly reduction of hot flushes. Results: Five randomized clinical trials, including 1482 postmenopausal women, were analyzed. Significant heterogeneity (I 2 = 90%) between studies was noted. Hot flushes episodes were significantly reduced in the treatment arm compared to placebo (mean difference (MD) -7.97 [-10.51, -5.92] episodes/week). Results on the improvement on sleep were limited by being reported in only two studies; however, no significant reduction of night-time awakenings was observed (MD, -0.40 awakenings/night [-1.38, 0.58 CI]). Conclusions: Low-dose paroxetine is an effective treatment for vasomotor menopause symptoms, including hot flushes.

Background: The aim of this study was to evaluate the diagnostic accuracy of endocervicoscopy as a preoperative examination to improve the outcome of the excisional treatment (LEEP) of high-grade cervical preneoplastic lesions., Methods: Patients with histologic diagnosis of CIN II-CIN III undergoing LEEP divided in two groups: in group A (85 women) a preoperative endocervicoscopy was performed, in group B (85 women) no additional examination was performed before LEEP. The size of the surgical specimen (H, D, W) and the margins of the lesion were evaluated., Results: Seventy-four women in group A and 80 in group B completed the follow-up. group A showed significant correlation between colposcopic examination and endocervicoscopic examination (P=0.001, k=0.30) and between endocervicoscopic and definitive histological examination (P<0.05, k=0.16). The depth of the operative sample was significantly lower (P<0.0001) in group A (0.91±0.4) than in group B (1.58±0.2), group A showed fewer patients B with positive endocervical margins than group B (3 vs. 17, P<002). Colposcopic, cytological and virological follow-up did not show significant differences between the two groups., Conclusions: Endocervicoscopy as preoperative tool for excisional treatment of cervical lesions showed high diagnostic effectiveness and allows to perform a conservative surgery.

Purpose: Contradictory reports exist in the literature regarding an association of cadmium with parameters of semen quality. The aim of the study was to assess cadmium levels in both blood and seminal plasma and to analyze the relationships between cadmium concentrations and lifestyle and semen parameters., Material and Methods: Fifty healthy male volunteers were recruited to provide semen and blood samples. Each patient completed an extensive questionnaire regarding his occupation, residence, social status, diet, water source, smoking habits, and medical and surgical history. Semen analysis was carried out according to WHO guidelines. Detection of cadmium in both semen and blood samples was carried out by means of atomic absorption spectrophotometer., Results: Mean concentrations of cadmium were 8.18 ± 1.6 ng/ml in blood samples and 2.56 ± 0.9 ng/ml in semen samples. Cadmium blood levels were significantly higher in men from industrialized areas and in current smokers, but were not correlated with semen levels. A significant positive correlation was found between cadmium blood levels, number of immotile spermatozoa, and teratozoospermia index (TZI). Significant inverse relationships between cadmium blood concentration and type-a and type a + b motility were found., Conclusions: The present data show a significant correlation between blood cadmium concentrations, cigarette smoking, occupational exposure, and parameters of semen quality. Such a reduction in spermiogenetic function could be an early marker of a toxic effect by cadmium pollution.

Aim: Persistent infection with high-risk Human Papilloma Virus (HPV) types is considered necessary for the development of cervical cancer. No such efficient antiviral agent exists at the present time. The aim of this study was to assess whether the use of topical products, vaginal ovules, containing betulinic acid and betulin may influence viral replication in vivo by promoting its negativity., Methods: We enrolled 62 patients at the colposcopy ambulatory with negative colposcopy or with congenital ectopic or normal transformation zone, but with HPV-test positive for high risk. We divided the patients into two groups: group A had no kind of treatment, group B has undergone a treatment with vaginal ovules containing betulinic acid and betulin. All patients have taken a new HPV-test six months after the first control., Results: After six months, we compared the percentage of negative HPV-test. We observed a percentage of negativity of 93% in group B versus 68% in group A. The data was statistically significant at χ2 test (P<0,05)., Conclusion: We believe that the results should be investigated further to confirm if there is a correlation between these substances and the increase in the rate of viral negativity.

Menopause is the interruption of menstrual and reproductive capacity, therefore, that occurs naturally in all women between 48 and 55 years, due to a lower production of gonadal steroids. The period becomes progressively irregular and lack of ovulation and menstrual flow decrease, and finally disappears. The time between the first symptoms and the cessation of the menstrual cycle is called menopause. With the onset of menopause the woman undergoes a series of changes related to estrogen deficiency, which occur in all tissues of the body. In this period one can distinguish an early stage, characterized by hot flashes, mood swings, night sweats and insomnia, and a late phase in which we highlight more symptoms related to the interruption of hormonal such as osteoporosis, obesity, at urogenital and increased incidence of cardiovascular disease. In Italy, only 5.2% of women aged 45-64 years used hormone replacement therapy, and only 20-30% follow a therapy for more than two years, both for psychological reasons, and for fear of side effects. Not surprisingly, therefore, phytoestrogens are given a high importance, as they are considered a natural alternative tank to to their plant origin. Interest in phytoestrogens was born from the observation that postmenopausal women who live in the East have a lower incidence of symptoms, cardiovascular disease, cancer and osteoporosis hormone use, compared to Western women.

Purpose: Metabolic syndrome and endothelial dysfunction play a relevant role in the cardiovascular risk in post-menopause. The aim of the study was to assess the effects of a low-dose hemihydrate estradiol and drospirenone combination on cardiovascular risk parameters in postmenopausal women with metabolic syndrome., Materials and Methods: Twenty-eight healthy women (group A) and 28 women with metabolic syndrome (group B) were treated with hemihydrate estradiol one mg + drospirenone two mg. At recruitment and after six months, clinical and laboratory parameters of metabolic syndrome were evaluated. Endothelial function was assessed measuring the flow-mediated dilatation of the brachial artery and the intima-media thickness of the common carotid artery., Results: After six months an overall improvement of metabolism was observed in both groups reaching statistical significance for triglycerides, total cholesterolemia, and systolic pressure in group B. A trend to lower baseline flow-mediated dilatation was also found in group B., Conclusions: Drospirenone improves cardiovascular risk factors and does not impair endothelial function in menopausal women with metabolic syndrome.

Aim: The aim of the study was to assess by what percentage the use of transvaginal ultrasound (TV, curettage) following voluntary interruption of pregnancy (IVG) reduces the incidence of haemorrhagic events resulting from incomplete drainage of the cavity during the first trimester of gestation., Methods: The present is a randomized prospective study involving 720 women who in the period between January 2005 and January 2007 underwent drainage of the cavity during the first trimester of gestation. The study group involved 360 women who were submitted to TV ultrasound using the Toshiba JustVision 400 system at the end of the surgical procedure. The control group also numbered 360 women; they, by contrast, did not undergo ultrasound examination at the end of surgery. In the study group, in those cases in which the ultrasound examination carried out with a TV probe highlighted an endometrial rima of thickness 8 mm, recurettage was carried out. Patients then underwent further gynecological and ultrasound control examination, 5-8 days after the surgical procedure., Results: The index of complications overall was 3.2%. Retained products of conception were encountered in 2 women in the study group (0.5%) and in 13 women from the control group (3.6%, P<0.05). Vaginal bleeding requiring hospitalization was observed in 2 women in the study group (0,5%) against 6 in the control group (1.6%, P=0.2). Cases of endometritis were diagnosed in only one woman in the study group (0.3%) against 5 in the control group (1.4%) and uterine perforation occurred in only one woman in the control group versus no case in the study group. There were no cases of retained products of conception in women presenting endometrial thickness <8 mm, a dimension obtained with the aid of ultrasound at the end of the surgical procedure., Conclusion: The use of ultrasound examination, carried out with the aid of a TV probe immediately following uterine drainage during the first trimester of pregnancy, may considerably reduce the incidence both of post-IVG haemorrhages due to incomplete curettage and of the total number of complications. Evaluation of endometrial thickness is of crucial importance. If this turns out to be =8 mm at the end of the surgical procedure, recurettage of the uterine cavity is indicated.

The term female adnexal tumor of probable Wolffian origin "FATWO" designs this tumor wich arises by the rare persisting remnants of the mesonephric duct (Wolffian duct). About 40 cases have been reported in literature. Few cases of recurrence have been reported, FATWO usually shows no signs of hormonal activity. We report a case of the youngest patient affected by FATWO in October 2002. At laparotomy the left adnexa were deformed by a well-capsulated mass, totally removed and sent to the pathologist with a specimen of peritoneal fluid and of the omentum. The histological examination showed a prevalent tubular structure with focal retiform area, without intraluminal mucines. Immunohistochemical findings of the case reported are similar to those described by other authors, except for inhibin which has not been detected by us. The cytofluorimetry showed the low presence of aneuploid cells, with a very low prolifing component (< 1%).