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Background/objectives: Microbiota modification at the endometrial level can favor gynecological diseases and impair women's fertility. The overgrowth of pathogen microorganisms is related to the contemporary alteration of estrogen-metabolizing bacteria, including β-glucuronidase, thereby enhancing estrogen-related inflammatory states and decreasing anti-inflammatory cells. The possible connection between estrobolome impairment and gynecological diseases has been suggested in animal models. Nevertheless, in humans, coherent evidence on the estrobolome alteration and functionality of the female reproductive tract is still lacking. The objective of this study was to explore alterations in estrogen-related signaling and the putative link with endometrial dysbiosis., Methods: Women with infertility and repeated implantation failure (RIF, N = 40) were enrolled in order to explore the putative link between estrogen metabolism and endometrial dysbiosis. Endometrial biopsies were used to measure inflammatory and growth factor molecules. β-glucuronidase enzyme activity and estrogen receptor (ER) expression were also assessed., Results: Herein, increased levels of inflammatory molecules (i.e., IL-1β and HIF-1α) and decreased levels of the growth factor IGF-1 were found in the endometrial biopsies of patients presenting dysbiosis compared to eubiotic ones. β-glucuronidase activity and the expression of ERβ were significantly enhanced in patients in the dysbiosis group. Interestingly, Lactobacilli abundance was inversely related to β-glucuronidase activity and to ERβ expression, thus suggesting that an alteration of the estrogen-activating enzyme may affect the expression of ERs as well., Conclusions: Overall, these preliminary data suggested a link between endometrial dysbiosis and estrobolome impairment as possible synergistic contributing factors to women infertility and RIF.

The decline in children's vaccination coverage and the resurgence of preventable infectious diseases draw attention to parents' vaccine hesitancy. Our study introduces two validated tools to independently assess vaccine hesitancy and health literacy among parents with school-age children. We developed a Vaccine Confidence Index (VCI) from 10 Likert items, exploring their relationships through exploratory and confirmatory factor analyses. We modified the IMETER (Italian medical term recognition test) to measure health literacy. We assessed the internal consistency of the modified IMETER and the 10 Likert items using Cronbach's alpha test (α) and McDonald's omega total coefficient (ω) with good results (ω = 0.92, α = 0.90; ω = 0.87, α = 0.82 respectively). We used these tools within a questionnaire conducted on 743 parents recruited from pediatric clinic waiting rooms in Italy, collecting demographic data, information sources on vaccines and vaccine-preventable diseases knowledge. The VCI resulting from factor analyses consisted of six items on a ten-point Likert scale, reflecting the ratio of positive to negative items. The survey revealed significant variations in the VCI according to individual features such as education, use of social networks, or Health institutions as sources of information. Multivariate logistic regression identified an association between vaccine intention and the VCI. Health literacy was functional for 91.2% of participants, but knowledge about vaccine-preventable diseases was generally low. The VCI showed no significant association with health literacy and vaccine-preventable diseases knowledge. The VCI and the modified IMETER effectively assess vaccination attitude and health literacy, offering valuable public health tools for tailoring vaccination campaigns to hesitant population subgroups.

In dental clinics, the infections may be acquired through contaminated devices, air, and water. Aerosolized water may contain bacteria, grown into the biofilm of dental unit waterlines (DUWLs). We evaluated a disinfection method based on water osmosis and chlorination with chlorine dioxide (O-CD), applied to DUWL of five dental clinics. Municipal water was chlorinated with O-CD device before feeding all DUWLs. Samplings were performed on water/air samples in order to research total microbial counts at 22-37 °C, Pseudomonas aeruginosa , Legionella spp., and chlorine values. Water was collected from the taps, spittoons, and air/water syringes. Air was sampled before, during, and after 15 min of aerosolizing procedure. Legionella and P. aeruginosa resulted as absent in all water samples, which presented total microbial counts almost always at 0 CFU/mL. Mean values of total chlorine ranged from 0.18-0.23 mg/L. Air samples resulted as free from Legionella spp. and Pseudomonas aeruginosa. Total microbial counts decreased from the pre-aerosolizing (mean 2.1 × 10 2 CFU/m 3 ) to the post-aerosolizing samples (mean 1.5 × 10 CFU/m 3 ), while chlorine values increased from 0 to 0.06 mg/L. O-CD resulted as effective against the biofilm formation in DUWLs. The presence of residual activity of chlorine dioxide also allowed the bacteria reduction from air, at least at one meter from the aerosolizing source.

An abnormal endometrial microbiota has been suggested to impair the process of embryo implantation, thus leading to repeated implantation failure (RIF) in women undergoing in vitro fertilization (IVF). However, the molecular mechanisms linking uterine microbiota and IVF out-comes are still an open question. The aim of this cohort study was to outline the relationship between endometrial microbiota, inflammation and IVF outcomes. To this purpose, endometrial microbiota and selected components of the “cytokine network” were analyzed in women presenting RIF and divided between eubiosis and dysbiosis groups, according to the percentage of endometrial lactobacilli (≥90% or <90%, respectively). The Dysbiosis group presented significantly higher tissue concentrations of the inflammatory markers (IL-6, IL-1β, HIF-1α and COX-2) and significantly lower levels of the anti-inflammatory/well-being factors, IL-10 and IGF-1, with respect to women with eubiosis. Moreover, the Lactobacillus percentage was negatively related to the concentrations of the inflammatory molecules and positively related to IL-10/IGF-1. Interestingly, the number of IVF attempts was directly related to the levels of the inflammatory factors COX-2, IL-1β and HIF-1α in the eubiosis group. Overall, endometrial dysbiosis was demonstrated to be associated with inflammation-related endometrial changes affecting the process of embryo implantation, underlining the importance of assessing uterine microbiota in patients undergoing IVF.

Background: Vaccination of healthcare workers (HCWs) is a crucial element to overcome the COVID-19 pandemic. The aim of this survey was to assess attitudes, sources of information and practices among Italian Healthcare workers (HCWs) in relation to COVID-19 vaccination. Methods: From 19 February to 23 April 2021, an anonymous voluntary questionnaire was sent to the mailing list of the main National Health Service structures. Data were collected through the SurveyMonkey platform. Results: A total of 2137 HCWs answered. Hesitancy towards COVID-19 vaccination was more frequent in females, in those with lower concern about COVID-19, and in nurses, auxiliary nurses (AN) and healthcare assistants. Hesitant professionals were more likely to not recommend vaccination to their patients or relatives, while a high concern about COVID-19 was related to an increased rate of recommendation to family members. HCWs were mostly in favor of mandatory vaccination (61.22%). Female sex, a lower education level, greater hesitancy and refusal to adhere to flu vaccination campaigns were predictors influencing the aversion to mandatory vaccination. All categories of HCWs referred mainly to institutional sources of information, while scientific literature was more used by professionals working in the northern regions of Italy and in infection control, infectious diseases, emergencies and critical areas. HCWs working in south-central regions, nurses, AN, healthcare technicians, administrators and HCWs with a lower education level were more likely to rely on internet, television, newspapers, and the opinions of family and friends. Conclusions: Communication in support of COVID-19 immunization campaigns should consider the differences between the various HCWs professional categories in order to efficiently reach all professionals, including the most hesitant ones.

Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The Epithelial-Mesenchymal Transition (EMT), an inflammation-related process, can be a further contributing factor to EMS. This study aimed to investigate, among various cytokines and EMT markers (Cadherins, TGF-β, HIF-1α), diagnostic markers of EMS and prognostic factors of in vitro fertilization (IVF) outcomes. Herein, EMS patients manifested higher serum levels of the inflammatory molecules IL-6, IL-8, and IL-12 and a decrease in the concentrations of the anti-inflammatory IL-10. Moreover, biochemical markers associated with the EMT process were more elevated in serum and follicular fluid (FF) of EMS patients than in controls. At the end, the number of good-quality embryos was inversely related to serum IL-6 and EMT markers. Interestingly, serum IL-6 and FF IL-10 concentrations differentiated EMS patients from controls. Finally, serum IL-8 and E-Cadherin levels, as well as FF IL-10, predicted positive IVF outcome with great accuracy. Our data confirm the pivotal role of inflammatory mediators (i.e., IL-6 and IL-10) in EMS pathogenesis and suggest that EMT-related markers are elevated in EMS patients and can be predictive of IVF outcome.

Three generations of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs) have been developed for treating advanced/metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations, while a fourth generation is undergoing preclinical assessment. Although initially effective, acquired resistance to EGFR-TKIs usually arises within a year due to the emergence of clones harboring multiple resistance mechanisms. Therefore, the combination of EGFR-TKIs with other therapeutic agents has emerged as a potential strategy to overcome resistance and improve clinical outcomes. However, results obtained so far are ambiguous and ideal therapies for patients who experience disease progression during treatment with EGFR-TKIs remain elusive. This review provides an updated landscape of EGFR-TKIs, along with a description of the mechanisms causing resistance to these drugs. Moreover, it discusses the current knowledge, limitations, and future perspective regarding the use of EGFR-TKIs in combination with other anticancer agents, supporting the need for bench-to-bedside approaches in selected populations., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Endoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases., Objectives: To evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG., Setting: Retrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center., Methods: EID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)-guided deployment of DPS or lumen apposing metal stents., Results: A total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818)., Conclusion: Early EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Study Objective: To show feasibility of using indocyanine green (ICG) in endometriosis surgery, especially bowel endometriosis shaving, and to discuss its potential benefits., Design: Stepwise demonstration of this technique with narrated video footage., Setting: Endometriosis is a common benign chronic disorder, characterized by the presence of endometrial tissue outside the uterus. Deep infiltrating endometriosis (DIE) represents the most aggressive presentation. Robot-assisted laparoscopy represents an important innovation and has opened new perspectives for the treatment of endometriosis, offering numerous advantages especially in the most complex procedures, particularly when extragenital endometriosis diffusely involves pelvic structures including the bowel and the urinary tract [1]. Endometriosis affects the bowel in 30% of DIE cases, and it is usually associated with ovarian and ureteral involvement; therefore, a multidisciplinary team with both general and gynecologic surgeons is required. The goal of endometriosis surgery in these cases is to obtain long-term outcomes without compromising intestinal function. One possible treatment is laparoscopic shave excision, which consists of dissection, keeping it as superficial as possible to avoid compromising bowel integrity [2]. Recent studies have shown that ICG can be useful to evaluate the size and depth of penetration of lesions during endometriosis surgery to understand shaving excision and to prevent a major iatrogenic intestinal complication [3-7]., Interventions: Total robot-assisted laparoscopic approach to a DIE case with adnexal, uterine, and intestinal endometriosis, with the presence of a nodular rectal lesion. The excision consisted of several key strategies to minimize iatrogenic rectal injury: CONCLUSION: The approach to DIE, particularly rectal endometriotic lesions, could be more accurate with ICG evaluation of vascular pertinence, in attempt to evaluate shaving feasibility of lesions in endometriosis laparoscopic robotic surgery., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of EGFR -mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR-21, miR-27a and miR-181a) as a surrogate for predicting EGFR-TKI performance in EGFR -mutated NSCLC patients., Methods: Plasma samples of 39 advanced EGFR -mutated NSCLC patients treated with EGFR-TKIs were collected at different points in time and miRNA levels were assessed by RT-PCR., Results: Higher basal values of miR-21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) ( p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR-21 ( p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR-TKI treatment showed that patients who experienced SD had an increase in miR-21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR ( p = 0.029). The same tendency was observed for miR-27a (FC = 3.1) and miR-181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR-21 levels in NSCLC cells that became resistant after exposure to EGFR-TKIs., Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR-21, and their dynamic change over time in predicting EGFR-TKI response in EGFR -mutated NSCLC.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive tumor characterized by early invasiveness, rapid progression and resistance to treatment. For more than twenty years, gemcitabine has been the main therapy for PDAC both in the palliative and adjuvant setting. After the introduction of FOLFIRINOX as an upfront treatment for metastatic disease, gemcitabine is still commonly used in combination with nab-paclitaxel as an alternative first-line regimen, as well as a monotherapy in elderly patients unfit for combination chemotherapy. As a hydrophilic nucleoside analogue, gemcitabine requires nucleoside transporters to permeate the plasma membrane, and a major role in the uptake of this drug is played by human equilibrative nucleoside transporter 1 (hENT-1). Several studies have proposed hENT-1 as a biomarker for gemcitabine efficacy in PDAC. A recent comprehensive multimodal analysis of hENT-1 status evaluated its predictive role by both immunohistochemistry (with five different antibodies), and quantitative-PCR, supporting the use of the 10D7G2 antibody. High hENT-1 levels observed with this antibody were associated with prolonged disease-free status and overall-survival in patients receiving gemcitabine adjuvant chemotherapy. This commentary aims to critically discuss this analysis and lists molecular factors influencing hENT-1 expression. Improved knowledge on these factors should help the identification of subgroups of patients who may benefit from specific therapies and overcome the limitations of traditional biomarker studies.

In Italy, the coronavirus disease 2019 (COVID-19) emergency took hold in Lombardy and Veneto at the end of February 2020 and spread unevenly among the other regions in the following weeks. In Tuscany, the progressive increase of hospitalized COVID-19 patients required the set-up of a regional task force to prepare for and effectively respond to the emergency. In this case report, we aim to describe the key elements that have been identified and implemented in our center, a 1082-bed hospital located in the Pisa district, to rapidly respond to the COVID-19 outbreak in order to guarantee safety of patients and healthcare workers.

Insulin resistance (IR) plays a central role in the onset of polycystic ovary syndrome (PCOS). Insulin so insulin-sensitizing like inositols have been proposed as first line therapy. Among them d-chiro-inositol (DCI) seems to improve glucose metabolism and to increase ovulation frequency. Other studies have demonstrated that alpha-lipoic acid (ALA), with its antioxidant role, can also improve endocrine and metabolic profile of PCOS patients especially with familial diabetes. This a retrospective observational study with the aim to evaluate possible advantages of an integrative preparation combining DCI 500 mg and ALA 300 mg in overweight/obese PCOS patients with or without diabetic relatives who underwent IVF. Twenty PCOS patients who were taking the integrative preparation underwent controlled ovarian hyperstimulation in our center. The group with diabetic relatives tended to have a lower dose of gonadotropin, shorter stimulation days, higher number of MII oocytes, and higher number of fertilized oocytes. A combined regimen of DCI and ALA could be an interesting strategy in overweight PCOS patients with familial diabetes underwent ART.

Background: The therapeutic value of lymphadenectomy in early stage endometrial cancer (EC) is still debated. Sentinel-lymph-node identified with indocyanine green (ICG) can replace lymphadenectomy in the staging of endometrial cancer minimizing the potential morbidity of a complete lymphadenectomy. The aim of this study was to analyze our initial experience using indocyanine green for sentinel-lymph-node mapping in a minimally robotic-assisted laparoscopic approach with Da Vinci XI near-infrared (NIR) fluorescence imaging system., Methods: A total of 23 patients who underwent robot-assisted laparoscopic surgery with the Da Vinci Xi Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) with NIR imaging and ICG fluorescence detection for early stage EC were retrospectively analyzed., Results: Sentinel-lymph-node mapping was achieved in 18 patients for a detection rate of 78.26%, bilateral pelvic detection was possible in 14 patients (60.9%) and no sentinel-lymph-node mapping was noted in 4 patients (17.4%). We compared 11 patients (Group 1) at intermediate and high- risk of recurrence who underwent sentinel-lymph- node mapping and pelvic lymphadenectomy and 12 patients (Group 2) at low risk of recurrence who underwent only sentinel-lymph-node mapping. A statistically significant difference was found for the average operation time and for the hospital stays., Conclusions: The high detection rate, absence of intraoperative or postoperative complications, the short time required for mapping and removal of the sentinel-lymph-nodes and the short duration of the hospital stay, support performing sentinel-lymph-node in all women with early endometrial cancer., (Copyright © 2019 Facts, Views & Vision.)

Background: Simulation in laparoscopic surgery is nowadays recognized as a valid instrument for learning and training surgeons in different procedures. However, its role as evaluation test and self-assessment tool to verify basic surgical skills is still under discussion., Methods: Thirty-three residents in obstetrics and gynecology at University of Pisa, Italy were recruited, and they received a simulation program consisting of 5 tasks. They had to perform basic laparoscopic surgery maneuvers as creating pneumoperitoneum, positioning trocars under vision, demonstrating the appropriate use of dominant and non-dominant hand and making single stitch and knot. They were evaluated with a modified OSATs scale., Results: Senior trainees had better score than junior trainees (p value< 0,005) and after different sessions of simulation scores of both groups significantly improved (p < 0,001), especially for the junior group. All the trainees reported self-assessments that matched with the evaluation of external observers demonstrating the importance of simulation also as auto-evaluation test., Conclusions: In this study, we demonstrated the role of simulation as powerful tool to evaluate and to self-assess surgical technical skills and to improve own capacities, with the use of a modified OSATs scale adapted to specific exercises.

Over the past four decades, the postponement of childbearing has continued to increase, significantly impacting the age of first-time mothers. Female age is the most significant factor influencing clinical outcome in in-vitro fertilization. To overcome the limits of the age-related decline of fertility is a challenge for fertility experts. In the decrease of fertility in late reproductive age, a lot of factors related with advancing women's age and general health can be considered, however the dominant regulator of this age-dependent loss of fertility is the ovary. The key factors in the ovarian aging are oxidative stress, abnormalities of the meiotic spindle, decrease of function and number of oocyte mitochondria, alteration of sirtuins and androgen deficiency. The aim of this review was to assess the main biological factors involved in the female reproductive ageing according to the recent literature, focusing on oocyte-dependent ones, as well as the possible therapeutic strategies in assisted reproductive technique.

Controlled ovarian stimulation (COH) in PCOS is a challenge for fertility expert both ovarian hyperstimulation syndrome (OHSS) and oocytes immaturity are the two major complication. Ovarian response to COH vary widely among POCS patients and while some patients are more likely to show resistance to COH, other experienced an exaggerated response. The aim of our study is to investigate a possible correlation between PCOS phenotypes and the variety of ovarian response to COH and ART outcomes in patients with different PCOS phenotypes. We retrospectively analyzed a total of 71 cycles performed in 44 PCOS infertile patients attending ART at Centre of Infertility and Assisted Reproduction of Pisa University between January 2013 and January 2016. Patientsundergoing IVF with GnRH-antagonist protocol and 150-225 UI/days of recombinant FSH; triggering was carried out using 250 mg of recombinant hCG or a GnRH analogous on the basis of the risk to OHSS. We observed that Phenotype B had a tendency to have a greater doses of gonadotropins used respect to all phenotypes. Phenotype A group showed a greater serum estrogen levels compared to all phenotypes groups, a greater number of follicles of diameter between 8-12 mm found by ultrasound on the day of triggering and a greater mean number of freeze embryo. Additionally serum AMH and antral follicles count (AFC) follow the same trend in the different phenotypes ad they were significantly higher in phenotype A and in phenotype D. In conclusion this study shows that the features of PCOS phenotypes reflect the variety of ovarian response to COH as well as the risks to develop OHSS. Serum AMH and AFC are related to the degree of ovulatory dysfunction making these 'added values' in identifying the different PCOS phenotypes. Phenotype A seems to be the phenotype with the higher risk to develop OHSS and the use of GnRH as a trigger seems to improve oocyte quality. To classify PCOS phenotype at diagnosis might help clinicians to identify patients at greater risk of OHSS, customize therapy and subsequently plan the trigger agent.

Introduction: Polycystic ovary syndrome (PCOS) is a common cause of female infertility affecting multiple aspects of a women's health., Areas Covered: The aim of this review is to summarize the existing evidence on the treatment of PCOS patients and to examine the actual available therapies to overcome the problem of infertility and improve the outcome of pregnancy. We analyse different treatment strategies such as lifestyle modification, bariatric surgery, insulin sensitizing agents, inositol, clomiphene citrate (CC), aromatase inhibitors, gonadotrophins, laparoscopic ovarian drilling, and assisted reproductive techniques (ART)., Expert Commentary: Lifestyle modification is the best initial management for obese PCOS patients seeking pregnancy and insulin sensitizing agents seem to have an important role in treating insulin resistance. Up to now, CC maintains a central role in the induction of ovulation and it has been confirmed as the first-line treatment; the use of gonadotrophins is considered the second-line in CC resistant patients; laparoscopic ovarian drilling is an alternative to gonadotrophins in patients who need laparoscopy for another reason. However, in anovulatory patients, ART represents the only possible alternative to obtain pregnancy. Larger and well-designed studies are needed to clarify the best way to improve the outcome of pregnancy in PCOS women.

The advent of robot-assisted laparoscopy (RAL) is an important innovation which has provided new perspectives for the treatment of endometriosis, and particularly of deep infiltrating endometriosis (DIE). RAL offers several technical advantages in the treatment of this complex disease, such as 3D view, tremor filtration and better surgical ergonomics, thus improving surgical performances without no increase in surgical time, blood loss, and intra- or postoperative complications, while also reducing the rate of conversion to laparotomy. Additionally, thanks to its reduced learning curve compared to conventional laparoscopy (CL), it facilitates the training of less experienced surgeons. For these reasons, DIE might be one of the best indications for RAL in gynecologic surgery. However, very few retrospective studies and small cases series, and only one randomized clinical trial have been published in this regard. Further randomized control trials comparing CL to RAL for different stages of endometriosis and different procedures performed are warranted in order to be able to define potential benefits of RAL for endometriosis surgery.

Recently, studies on inositol supplementation during in vitro fertilization program (IVF) have gained particular importance due to the effect of this molecule on reducing insulin resistance improving ovarian function, oocyte quality, and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoforms, especially myoinositol (MYO), are often used as prestimulation therapy in infertile patients undergoing IVF cycle. Inositol supplementation started three months before ovarian stimulation, resulting in significant improvements in hormonal responses, reducing the amount of FSH necessary for optimal follicle development and serum levels of 17beta-estradiol measured the day of hCG injection. As shown by growing number of trials, MYO supplementation improves oocyte quality by reducing the number of degenerated and immature oocytes, in this way increasing the quality of embryos produced. Inositol can also improve the quality of sperm parameters in those patients affected by oligoasthenoteratozoospermia.

Anatomical uterine element and functional components play a fundamental role in the enhancing of fertility are the major actors. Uterine pathologies, including congenital or acquired lesions, have been reported in 21 to 47% of patients undergoing in vitro fertilization cycles. Hysteroscopy is an important procedure in the study of one of the most important element of fertility: the uterus, even if its use in the world of infertility is discussed. There are many studies on safety and feasibility of the procedure and on patient compliance, but there is no consensus on its systemic use. This study, thanks to the wide literature about the use of hysteroscopic surgery to enhance fertility in most of the congenital and acquired problems affecting women in fertility age, allows defining that diagnostic and operative hysteroscopy is a rapid and safety technology to improve fertility.

Objective: To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of polycystic ovary syndrome (PCOS) patients., Design: Controlled clinical study., Setting: PCOS patients in a clinical research environment., Patients: 50 overweight PCOS patients were enrolled after informed consent., Interventions: All patients underwent hormonal evaluations and an oral glucose tolerance test (OGTT) before and after 12 weeks of therapy (Group A (n¼10): MYO 2 g plus folic acid 200 mg every day; Group B (n¼10): folic acid 200 mg every day). Ultrasound examinations and Ferriman-Gallwey score were also performed., Main Outcome Measures: Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio., Results: After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid., Conclusions: MYO administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.

Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 5-20% of women during the age of fertility. Prevalence of thyroid autoimmunity is significantly higher among infertile women, especially when the cause of infertility is endometriosis or polycystic ovary syndrome. Presence of thyroid autoimmunity does not interfere with normal embryo implantation and have been observed comparable pregnancy rates after assisted reproduction techniques in patients with or without thyroid autoimmunity. Instead, the risk of early miscarriage is substantially raised with the presence of thyroid autoimmunity, even if there was a condition of euthyroidism before pregnancy. Furthermore the controlled ovarian hyperstimulation, used as preparation for assisted reproduction techniques, can severely impair thyroid function increasing circulating estrogen levels. Systematic screening for thyroid disorders in women with a female cause of infertility is controversial but might be important to detect thyroid autoimmunity before to use assisted reproduction techniques and to follow-up these parameters in these patients after controlled ovarian hyperstimulation and during pregnancy.

Objective: To analyze the effect of dehydroepiandrosterone (DHEA) supplementation on follicular microenvironment and on in vitro fertilization (IVF) outcomes among poor responder patients., Study Design: We enrolled 24 patients diagnosed as poor responders based on ESHRE consensus criteria. One group received 25 mg/die three times daily of DHEA supplementation for 3 months previous to IVF cycle, while the other did not receive any treatment. COH was performed with rFSH and hMG, and a GnRH antagonist was administered according to a flexible protocol. We evaluated perifollicular vascularization of recruited follicles through power Doppler blood flow analysis and follicles were graded as described by Chui et al. Follicular fluids (FF) from F3-F4 follicles were collected, and FF levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor1 (HIF1) were measured., Results: FF levels of HIF1 were statistically significant lower in women treated with DHEA (14.76 ± 51.13 vs. 270.03 ± 262.18 pg/ml; p = 0.002). On the contrary, VEGF levels did not differ between the two groups. Concerning COH, in the DHEA-group the mean duration of treatment was significantly shorter (9.83 ± 1.85 vs. 12.09 ± 2.81; p = 0.023). Total numbers of oocytes retrieved, fertilized oocytes, good quality embryos, number of transferred embryos and clinical pregnancies tended to be higher in study group, but the results were not significant. On the other hand, considering the oocytes retrieved in selected F3-F4 follicles, there was a relation between HIF1 levels and oocytes quality. In fact, mature oocytes retrieved in selected follicles were significantly more numerous in DHEA-group (0.50 ± 0.52 vs. 0.08 ± 0.29; p = 0.018)., Conclusions: The improvement of reproductive parameters after DHEA supplementation in poor responders may be explained through the effect that this pro-hormone exerts on follicular microenvironment.

A large number of experimental and clinical studies published in recent years have demonstrated the beneficial role of probiotic bacteria in the health of the host. However, because the different receptors of the innate immune system can recognize only specific bacterial molecular patterns, knowledge of the role played by individual probiotic molecular patterns is essential to move from the current confused era of live probiotic bacteria to the era of the pharmacobiotic strategies. This article reviews the current knowledge on the probiotic activities of bacterial structural molecules (nucleic acids and surface molecules), which represent the fundamental basis to set up experimental and clinical studies in this emerging field with very promising and potentially invaluable future prospects.

Aim of the Study: To report the frequency of aberrant karyotype and mutated cystic fibrosis transmembrane conductance regulator (CFTR) gene, according to a careful application of Italian guidelines for genetic screening in infertile couple candidates for intrauterine insemination (IUI) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)., Materials and Methods: Two thousand and sixteen consecutive infertile couple candidates for Assisted Reproduction Techniques (ART) were screened for karyotype and 616 couples for CFTR analysis., Results: Regarding karyotype analysis, 59 chromosomal abnormalities were diagnosed in candidates for IVF/ICSI: 27 mutations in women corresponding to a frequency equal to 1.53% (27/1762; 95% confidence interval [CI], 0.96-2.1%) and 32 mutations in men corresponding to a frequency equal to 1.82% (32/1762; 95% CI, 1.2-2.44%) for men. The frequency differs according to the sperm count. In couple candidates for IUI techniques, no genetic abnormalities were found in male patients and only one aberration in a female patient with a frequency of 0.41% (1/245 CI 0.01-0.81%). Regarding CFTR analysis, excluding the 5T variant, we obtained 20 mutations in couples undergoing IVF/ICSI and 8 mutations in IUI group., Conclusion: Couples undergoing IVF/ICSI show a higher prevalence of aberrant karyotypes than general population, whereas the frequency of a mutation of the CFTR gene is similar. On the other hand, couples undergoing IUI do not differ from the general population either for karyotype or for CFTR mutations.

This study evaluated whether heparin administration could affect IVF outcome. A total of 172 women, aged <40years, without laboratory findings of thrombophilia and undergoing their first IVF cycle, were randomly allocated to treatment (n=86) and control (n=86) groups. Patients allocated to the treatment group received low-molecular-weight heparin dalteparin sodium 2500IU s.c. daily, in addition to routine luteal phase support, from oocyte retrieval up to the day of the pregnancy test or up to the ninth week of pregnancy in the cases of positive human chorionic gonadotrophin. From the day after the oocyte retrieval, all patients began standard supplementation with vaginal progesterone 200mg twice a day. At the sixth week of pregnancy, patients underwent an ultrasound scan to assess the number/viability of gestational sacs. Implantation rates were 15% and 12% in the dalteparin and control groups, respectively. The clinical pregnancy rates/embryo transfers were 26% (19/73) and 20% (16/80), in the dalteparin and control groups, respectively, with live birth rates/embryo transfer of 21% (15/73) and 16% (13/80). Despite the lack of statistical significance, the increase in pregnancies observed in the treatment group may be considered as an important clinical point in the optimization of IVF clinical outcome., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Importance of the Field: One of the main objectives in assisted reproduction techiques (ART) is the maturation of multiple follicles and the recovery of multiple good quality oocytes. To realize this, it is necessary to interfere with the mechanisms of selection and follicular dominance, characteristic of spontaneous mono-ovulatory cycles, by administering gonadotrophins. In 12 - 20% of the stimulation cycles, the response to ovarian stimulation in terms of follicular development is higher than expected, with the onset of the so-called ovarian hyperstimulation syndrome (OHSS). This is considered to be an exaggerated response: an iatrogenic - possibly life-threatening - complication of ovarian stimulation., Areas Covered in This Review: This review deals about reproductive, obstetric and gynecological aspects of OHSS., What the Reader Will Gain: Understanding the pathophysiology of OHSS is the key to establishing a correct pharmacotherapy. However, the mechanisms underlying OHSS have not yet been completely clarified. Treatment of OHSS is empirical, so prevention is the most important aspect in its management. Several studies support the role of vascular endothelial growth factor in the development of OHSS in humans, so future studies about anti-angiogenetic molecules seem to be an important goal in ART., Take Home Message: Methods to prevent OHSS.

Premature ovarian failure is a complex disorder that results in the early loss of ovarian function; however this disease must be separated from early menopause because these patients can sporadically ovulate and in literature are described pregnancies. The aetiology and the patho-physiology of premature ovarian failure are still matter of debate, but is commonly accepted that genetic factors play an important role. This review is aimed to present an overview of known inherited factor implied in the pathogenesis of this disorder to help physician in the counselling of affected pregnant women.

The polycystic ovarian syndrome (PCOS) includes a wide spectrum of clinical symptoms and signs. Three different diagnostic classifications have been proposed to define this disease. The first one, published in 1990, known as the "NIH criteria" requires the simultaneous presence of hyperandrogenism and menstrual dysfunction in order to diagnose PCOS. Later on, in 2003, an expert panel met in Rotterdam and added to the previous criteria the presence of polycystic ovarian morphology detected by transvaginal ultrasonography. The later classification broadened the spectrum of PCOS and also included women with oligomenorrhea and PCO without hyperandrogenism or hyperandrogenism and PCO without menstrual dysfunction. Finally, the Androgen Excess Society, published in 2006 new diagnostic criteria which required the presence of clinical or biochemical hyperandrogenism, with either PCO or menstrual dysfunction to diagnose PCOS. This review focuses on the diagnostic techniques and methods of treatment for PCOS patients. Special attention is given to the role of insulin resistance and the potential utility of insulin sensitizers in management of the syndrome. The benefit and utmost importance of lifestyle modification for the long-term health of these women is stressed as well. It is hoped that some clarity in this regard will allow more women to not only be diagnosed and managed properly for their presenting symptoms (hirsutism, irregular menses, etc.), but also to be educated and managed for the continuing health risk of insulin resistance throughout their lives.

Background: Inflammatory myoglandular polyp (IMGP) is a rare non-neoplastic polyp of the large bowel, commonly with a distal localization (rectosigmoid), obscure in its pathogenesis. Up till now, 60 cases of IMGP have been described in the literature, but none located in the cecum., Case Presentation: We report a case of a 53-year-old man who was admitted to our hospital for further evaluation of positive fecal occult blood test associated to anemia. A colonoscopy identified a red, sessile, lobulated polyp of the cecum, 4.2 cm in diameter, partially ulcerated. The histological examination of the biopsy revealed the presence of inflammatory granulation tissue with lymphocytic and eosinophil infiltration associated to a fibrous stroma: it was diagnosed as inflammatory fibroid polyp. Considering the polyp's features (absence of a peduncle and size) that could increase the risk of a polypectomy, a surgical resection was performed. Histological examination of the specimen revealed inflammatory granulation tissue in the lamina propria, hyperplastic glands with cystic dilatations, proliferation of smooth muscle and multiple erosions on the polyp surface: this polyp was finally diagnosed as IMGP. There was also another little polyp next to the ileocecal valve, not revealed at the colonoscopy, 0.8 cm in diameter, diagnosed as tubulovillous adenoma with low grade dysplasia., Conclusions: This is the first case of IMGP of the cecum. It is a benign lesion of unknown pathogenesis and must be considered different from other non-neoplastic polyps of the large bowel such as inflammatory cap polyps (ICP), inflammatory cloacogenic polyps, juvenile polyps (JP), inflammatory fibroid polyps (IFP), polyps secondary to mucosal prolapse syndrome (MPS), polypoid prolapsing mucosal folds of diverticular disease. When symptomatic, IMGP should be removed endoscopically, whereas surgical resection is reserved only in selected patients as in our case.

Background: The elevated serum and peritoneal cytokine concentrations responsible for the systemic response syndrome (SIRS) and multiorgan failure in patients with severe acute pancreatitis lead to high morbidity and mortality rates. Prompted by reports underlining the importance of reducing circulating inflammatory mediators in severe acute pancreatitis, we designed this study to evaluate the efficiency of laparotomy followed by continuous perioperative peritoneal lavage combined with postoperative continuous venovenous diahemofiltration (CVVDH) in managing critically ill patients refractory to intensive care therapy. As the major clinical outcome variables we measured morbidity, mortality and changes in the Acute Physiology and Chronic Health Evaluation (APACHE II) score and cytokine concentrations in serum and peritoneal lavage fluid over time., Methods: From a consecutive group of 23 patients hospitalized for acute pancreatitis, we studied 6 patients all with Apache II scores >/=19, who underwent emergency surgery for acute complications (5 for an abdominal compartment syndrome and 1 for septic shock) followed by continuous perioperative peritoneal lavage and postoperative CVVDH. CVVDH was started within 12 hours after surgery and maintained for at least 72 hours, until the multiorgan dysfunction syndrome improved. Samples were collected from serum, peritoneal lavage fluid and CVVDH dialysate for cytokine assay. Apache II scores were measured daily and their association with cytokine levels was assessed., Results: All six patients tolerated CVVDH well, and the procedure lasted a mean 6 days (range, 3-12). Five patients survived and one died of Acinetobacter infection after surgery (mortality rate 16.6%). The mean APACHE II score was >/= 19 (range 19-22) before laparotomy and decreased significantly during peritoneal lavage and postoperative CVVDH (P = 0.013 by matched-pairs Students t-test). The decrease in cytokine concentrations in serum and lavage fluid was associated with the decrease in APACHE II scores and high interleukin 6 (IL-6) and tumor necrosis factor (TNF) concentrations in the hemofiltrate., Conclusion: In critically ill patients with abdominal compartment syndrome, septic shock or high APACHE II scores related to severe acute pancreatitis, combining emergency laparotomy with continuous perioperative peritoneal lavage followed by postoperative CVVHD effectively reduces the local and systemic cytokines responsible for multiorgan dysfunction syndrome thus improving patients' outcome.

A non cirrhotic patient with esophageal varices and portal vein thrombosis had recurrent variceal bleeding unsuccessfully controlled by endoscopy and esophageal transection. Emergency transhepatic portography confirmed the thrombosed right branch of the portal vein, while the left branch appeared angulated, shifted and stenotic. A stent was successfully implanted into the left branch and the collateral vessels along the epatoduodenal ligament disappeared. In patients with esophageal variceal hemorrhage and portal thrombosis if endoscopy fails, emergency esophageal transection or nonselective portocaval shunting are indicated. The rare patients with only partial portal thrombosis can be treated directly with stenting through an angioradiologic approach.

The detoxification and sterilization radicular surfaces that have been produced by periodontal diseases could be accomplished after polishing (root planing) using the thermal elevation resulting from CO2 laser on continuous emission. In vitro experiments reveal that thermal elevations reached on the surfaces or in the depth are proportional to the dispersed energy. The thermal elevation in the depth (0.5-1 mm from the impact point) remained moderate because of the water absorption potentials of the radiations. Energies from 2 to 4.5 J can help obtain the combination of surface temperature elevation, which allows detoxification, and of a thermal elevation in the depth, compatible with vital tissues. This energy has to be delivered at an application time under 0.6 sec in continuous mode.

Horned gena (Hg), a sex-linked dominant mutation with semilethal effects in the imago stage, was found in Tribolium confusion. The Hg mutant is characterized by a pair of horns of variable size and shape that arises from the genoclypeal suture in mildly expressed beetles or a more pronounced horn-like structure resulting from a folding of the genal shelf near the compound eyes. In these beetles there is considerable stress on the exoskeleton of the head so that the cranium is fragmented between the eyes, leaving large, irregularly shaped areas of the head unprotected by cranial exoskeleton. These beetles die presumably because of bacterial infection or because they cannot retain moisture within their bodies. This mutation differs from the mutation V-Grube found in another tenebrionid, Tenebrio molitor. Taxonomic, genetic, and cytological evidence is presented suggesting that Hg is a gene of ancient origin, having existed at least since the genera of Tenebrionidae were being evolved.