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Background: Contamination and transmission of different Listeria monocytogenes strains along food chain are a serious threat to public health and food safety. Understanding the distribution of diseases in time and space-time is fundamental in the epidemiological study and in preventive medicine programs. The aim of this study is to estimate listeriosis incidence along 10-years period and to perform space-time cluster analysis of listeriosis cases in Marche Region, Italy. Methods: The number of observed listeriosis cases/year was derived from regional data of surveillance of notifiable diseases and hospital discharge form. The capture and recapture method (C-R method) was applied to estimate the real incidence of listeriosis cases in Marche Region and the space-time scan statistics analysis was performed to detect clusters of space-time of listeriosis cases and add precision to the conventional epidemiological analysis. Results: The C-R method estimation of listeriosis cases was 119 in the 10- year period (2010–2019), with an average of 31.93 % of unobserved cases (lost cases). The estimated mean annual incidence of listeriosis was 0.77 per 100,000 inhabitants (95 %CI 0.65–0.92), accounting for 6.07 % of additional listeriosis cases per year than observed cases. Using the scan statistic, the two most likely clusters were identified, one of these was statistically significant (p

A 43-year-old patient with a history of uterine fibromatosis was referred to our hospital for menometrorrhagia and pelvic pain. At the pelvic ultrasound, a highly-vascularized myometrial lesion in volumetric increase was described. An elongated, solid, hypoechoic, painless, and highly vascularized left parauterine mass was identified. On histological examination, a uterine smooth muscle tumor of uncertain malignant potential (STUMP) with intravascular invasion of the left uterine vein was diagnosed. The adnexa and peritoneum were free of disease. On a retrospective evaluation of the ultrasound images, we noticed that the intravascular lesion showed sonographic features comparable to the original mass. Moreover, the Color Doppler (CD) analysis revealed an interrupted blood flow within the left uterine vein. In this case, the ultrasound proved to be an accurate diagnostic tool. When inhomogeneous uterine masses are suspected, and a parauterine/paraadnexal mass surrounded by irregular vessels are identified, the sonographer should take into account a risk of intravascular invasion. The patency of uterine and ovarian vessels should be accurately evaluated, to guide a tailored patient surgical approach.

AbstractObjective The objective of this study was to evaluate the attitude of obstetricians/gynecologists toward indicating an elective cesarean delivery in pregnant patients with a previous myomectomy.Materials and Methods Web-based multiple-choice questions survey evaluating the attitude to indicate a cesarean with a composite summated score (range 56–280) from a 56-item Likert scale: score 56–112: weak attitude, 113–168: moderate, 169–224: strong, and 225–280: very strong. The reliability of the score (internal consistency) was evaluated with Cronbach’s alpha coefficient. The association between the score and participants’ characteristics was determined with a bivariate analysis followed by linear regression analysis. The “global importance” of each risk factor was defined as the prevalence of the answers: “moderately important”, “very important”, and “extremely important” on the Likert scale. Factors with a “global importance” >75% were considered “crucial” in influencing the choice to indicate a cesarean.Results One-hundred-twenty obstetricians/gynecologists responded (response rate 70.6%). The mean ± SD composite summated score was 137 ± 31; 30 (25.0%) participants presented a "weak attitude to cesarean", 68 (56.7%) a "moderate attitude", 22 (18.3%) a "strong attitude", and none a "very strong attitude". The Cronbach’s alpha was 0.934 (high internal consistency). A self-reported number of myomectomies performed per year >50 was associated with a lower score (-25 points, 95% CI −50 to −1, p = 0.04). Eight criteria resulted “crucial” in indicating a cesarean: opening of the endometrial cavity, monopolar electrosurgery, time surgery-pregnancy

The HtrA serine peptidase 1 (HTRA1) is a multidomain secretory protein with serine–protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HTRA1 is normally expressed in the human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in the early phases of human placenta development. The aim of this study was to evaluate the functional role of HTRA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE). BeWo and HTR8/SVneo cells expressing HTRA1 were used as syncytiotrophoblast and cytotrophoblast models, respectively. Oxidative stress was induced by treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HTRA1 expression. In addition, HTRA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility, and invasion processes. Our main data showed that oxidative stress significantly increased HTRA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HTRA1 has a pivotal role in cell motility and invasion processes. In particular, HTRA1 overexpression increased while HTRA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. In conclusion, our results suggest an important role of HTRA1 in regulating extravillous cytotrophoblast invasion and motility during the early stage of placentation in the first trimester of gestation, suggesting a key role of this serine protease in PE onset.

Pregnancy is generally studied as a biological interaction between a mother and a fetus; however, the father, with his characteristics, lifestyle, genetics, and living environment, is by no means unrelated to the outcome of pregnancy. The half of the fetal genetic heritage of paternal derivation can be decisive in cases of inherited chromosomal disorders, and can be the result of de novo genetic alterations. In addition to the strictly pathological aspects, paternal genetics may transmit thrombophilic traits that affect the implantation and vascular construction of the feto-placental unit, lead to placenta-mediated diseases such as pre-eclampsia and fetal growth retardation, and contribute to the multifactorial genesis of preterm delivery. Biological aspects of immunological tolerance to paternal antigens also appear to be crucial for these pathologies. Finally, this review describes the biological findings by which the environment, exposure to pathogens, lifestyle, and nutritional style of the father affect fetal pathophysiological and epigenetic definition.

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget’s disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

Abstract Head and neck cancer, the sixth most common cancer worldwide, account for about 1 out of 20 malignant tumors. In recent years a reduction in the incidence of cervical cancer, but a concomitant major increase in the incidence of HPV-mediated oropharyngeal cancer caused by orogenital HPV transmission has been observed. Consequently, in wealthy countries oropharyngeal squamous-cell carcinomas (OPSCC) is now the most frequent HPV-related cancer, having overtaken cervical cancer. Without effective medical interventions, this incidence trend could continue for decades. As no specific precursor lesion has been consistently identified in the oral cavity and oropharynx, HPV vaccination is the logical intervention to successfully counteract also the rising incidence of OPSCCs. However, HPV vaccine uptake remains suboptimal, particularly in males, the population at higher risk of OPSCC. Alternative primary prevention measures, such as modifications in sexual behaviors, could be implemented based on knowledge of individual genital HPV status. Until recently, this information was not available at a population level, but the current gradual shift from cytology (Pap test) to primary HPV testing for cervical cancer screening is revealing the presence of oncogenic viral genotypes in millions of women. In the past, health authorities and professional organizations have not consistently recommended modifications in sexual behaviors to be adopted when a persistent high-risk HPV cervicovaginal infection was identified. However, given the above changing epidemiologic scenario and the recent availability of an immense amount of novel information on genital HPV infection, it is unclear whether patient counseling should change. The right of future partners to be informed of the risk could also be considered. However, any modification of the provided counseling should be based also on the actual likelihood of a beneficial effect on the incidence of HPV-associated oropharyngeal cancers. The risk is on one side to induce unjustified anxiety and provide ineffective instructions, on the other side to miss the opportunity to limit the spread of oral HPV infections. Thus, major health authorities and international gynecologic scientific societies should issue or update specific recommendations, also with the aim of preventing inconsistent health care professionals’ behaviors.

ObjectiveTo assess and compare the inter-rater agreement of the CDC criteria and the ASEPSIS score in identifying surgical site infections after cesarean section.MethodsProspective observational study including 110 patients subjected to a cesarean section at our institution. Surgical wounds were managed according to standard care and were photographed on the third, seventh, and thirtieth postoperative day or during any evaluation in case of complications. Three expert surgeons reviewed the prospectively gathered data and photographs and classified each wound using CDC criteria and the ASEPSIS score. The inter-rater agreements of CDC criteria and ASEPSIS score were determined with Krippendorff's Alpha with linear weights and compared with a confidence interval approach.ResultsThe weighted α coefficient for CDC criteria was 0.587 (95%CI, 0.411–0.763, p

Thrombotic microangiopathies (TMAs) comprise a distinct group of diseases with different manifestations that can occur in both pediatric and adult patients. They can be hereditary or acquired, with subtle onset or a rapidly progressive course, and they are particularly known for their morbidity and mortality. Pregnancy is a high-risk time for the development of several types of thrombotic microangiopathies. The three major syndromes are hemolysis, elevated liver function tests, and low platelets (HELLP); hemolytic uremic syndrome (HUS); and thrombotic thrombocytopenic purpura (TTP). Because of their rarity, clinical information and therapeutic results related to these conditions are often obtained from case reports, small series, registries, and reviews. The collection of individual observations, the evolution of diagnostic laboratories that have identified autoimmune and/or genetic abnormalities using von Willebrand factor post-secretion processing or genetic–functional alterations in the regulation of alternative complement pathways in some of these TMAs, and, most importantly, the introduction of advanced treatments, have enabled the preservation of affected organs and improved survival rates. Although TMAs may show different etiopathogenesis routes, they all show the presence of pathological lesions, which are characterized by endothelial damage and the formation of thrombi rich in platelets at the microvascular level, as a common denominator, and thrombotic damage to microcirculation pathways induces “mechanical” (microangiopathic) hemolytic anemia, the consumption of platelets, and ischemic organ damage. In this review, we highlight the current knowledge about the diagnosis and management of these complications during pregnancy.

Introduction: Colposcopy is an important part of the diagnostic work‐up of women with an abnormal cervical screening test as it is used to guide the collection of biopsies. Although quality assurance has been used in the evaluation of screening programs, not much is known about quality indicators for the diagnostics and treatment of screen‐positive women. Therefore, the European Federation for Colposcopy developed quality indicators aiming to support colposcopy practice across Europe. We performed a survey of colposcopy cases to determine if the quality indicators are understandable, relevant, and reproducible. Material and Methods: We conducted a survey among all members of the European Federation for Colposcopy Quality and Standards Group from November 2022 to March 2023. Members were asked to collect information on a total of 17 quality indicators for 50 women who had been newly referred for colposcopy due to an abnormal screening test between January 1, 2020 to December 31, 2021. Results were reported descriptively. Results: We included data on 609 cases from 12 members across Europe. The majority of the quality indicators were either achieved or within reach of the agreed standard, often due to few countries with outlying data. One quality indicator had very low performance, although stratified results indicated that two countries had different clinical management of the patient type thereby skewing the results. In addition, discrepancies between the number of cases included in each quality indicator raised concerns regarding potential misunderstanding of the quality indicator and its objective. Conclusions: Quality indicators on colposcopy must be understandable to those collecting data, highlighting the importance of validating quality indicators before data collection. [ABSTRACT FROM AUTHOR]

Luca Giannella,1 Giovanni Delli Carpini,1 Jacopo Di Giuseppe,1 Giorgio Bogani,2 Barbara Gardella,3 Ermelinda Monti,4 Carlo Antonio Liverani,4 Alessandro Ghelardi,5 Salvatore Insinga,1 Michele Montanari,1 Francesco Raspagliesi,2 Arsenio Spinillo,3 Paolo Vercellini,4 Elena Roncella,4 Andrea Ciavattini1 1Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Ancona, Italy; 2Gynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy; 3Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy; 4Gynaecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy; 5Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, Massa, ItalyCorrespondence: Andrea CiavattiniWoman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, via Filippo Corridoni, 16, Ancona, 60123, ItalyTel +390715962172Fax +3907136576Email ciavattini.a@libero.itAim: In the post-vaccination era, the starting age and time intervals of cervical screening could change (older age and longer screening intervals). This scenario may be achieved by significantly reducing human papillomavirus (HPV) 16/18 prevalence (genotypes included in the current vaccines). In this regard, assessing the trend over time of these HPV infections in high-grade cervical lesions can provide information on the objective. The present study aimed to evaluate the trend of HPV 16/18 over the years 2007– 2018 in women with cervical intraepithelial neoplasia (CIN) grade 3.Methods: This is a retrospective multi-institutional study including HPV genotyped and unvaccinated women under 30 with CIN3. The sample was divided into the following periods: 2007– 2010, 2011– 2014, 2015– 2018. HPV genotypes were grouped in genotypes 16/18, genotypes 31/33/35/52/58/67 (genetically related to HPV16), genotypes 39/45/59/68/70 (genetically related to HPV18), genotypes 31/33/45/52/58 (high-risk types included in the nonavalent vaccine), possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85), low-risk HPV (genotypes 6/11/40/42/43/44/54/55/61). The trend between periods and HPV genotypes was measured using the Cochran–Armitage test for trend.Results: The final analysis included 474 participants. HPV 16/18 prevalence decreased significantly over the years (77.8% vs 68.9% vs 66.0%, respectively, Ptrend=0.027). Possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85) showed a significant negative prevalence trend over time (4.9% vs 1.1% vs 1.3%, respectively, Ptrend=0.046). Finally, there was a significant positive trend over the years for high-risk HPV genotypes 31/33/45/52/58 in women under 25 (9.9% vs 17.0% vs 24.0%, respectively, Ptrend=0.048).Conclusion: The prevalence of CIN3 lesions related to HPV 16/18 genotypes decreased over time from 2007 to 2018. These data highlight a herd effect of the HPV vaccine. However, fifteen years after HPV vaccine introduction, we are still a long way from herd immunity. The increase in high-risk types 31/33/45/52/58 will need to be reassessed when the nonavalent vaccine impact will be more reliable.Keywords: cervical cancer, cervical intraepithelial neoplasia, cervical cancer screening program, HPV vaccine, HPV-16/18

Placentation is a key and tightly regulated process that ensures the normal development of the placenta and fetal growth. Preeclampsia (PE) is a hypertensive pregnancy-related disorder involving about 5–8% of all pregnancies and clinically characterized by de novo maternal hypertension and proteinuria. In addition, PE pregnancies are also characterized by increased oxidative stress and inflammation. The NRF2/KEAP1 signaling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. ROS activate NRF2, allowing its binding to the antioxidant response element (ARE) region present in the promoter of several antioxidant genes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase that neutralize ROS, protecting cells against oxidative stress damages. In this review, we analyze the current literature regarding the role of the NRF2/KEAP1 pathway in preeclamptic pregnancies, discussing the main cellular modulators of this pathway. Moreover, we also discuss the main natural and synthetic compounds that can regulate this pathway in in vivo and in vitro models.

Quality Control (QC) and Quality Assurance (QA) principles are essential for effective cervical cancer prevention. Being a crucial diagnostic step, colposcopy’s sensitivity and specificity improvements are strongly advocated worldwide since inter- and intra-observer differences are the main limiting factors. The objective of the present study was the evaluation of colposcopy accuracy through the results of a QC/QA assessment from a survey in Italian tertiary-level academic and teaching hospitals. A web-based, user-friendly platform based on 100 colposcopic digital images was forwarded to colposcopists with different levels of experience. Seventy-three participants were asked to identify colposcopic patterns, provide personal impressions, and indicate the correct clinical practice. The data were correlated with a panel of experts’ evaluation and with the clinical/pathological data of the cases. Overall sensitivity and specificity with the threshold of CIN2+ accounted for 73.7% and 87.7%, respectively, with minor differences between senior and junior candidates. Identification and interpretation of colposcopic patterns showed full agreement with the experts’ panel, ranging from 50% to 82%, in some instances with better results from junior colposcopists. Colposcopic impressions correlated with a 20% underestimation of CIN2+ lesions, with no differences linked to level of experience. Our results demonstrate the good diagnostic performance of colposcopy and the need for improving accuracy through QC assessments and adhesion to standard requirements and recommendations.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Simple Summary: Cervical cancer, a very aggressive gynecological malignancy that also affects young women, remains significantly prevalent despite worldwide efforts in HPV vaccination campaigns. Cervical cancer research is experiencing a period of significant change, with intense ongoing debates on issues that could potentially transform current guidelines. Therefore, in light of these changes, guidelines and protocols will soon need significant updates. Hence, this paper aims to summarize and compare the most recent recommendations published by international gynecological oncology societies for patients with cervical cancer. A comparative analysis of American, Asian, and European guidelines was conducted to evaluate the different recommendations for diagnostic, surgical, medical, and follow-up management. Cervical cancer continues to have a significant incidence, despite global efforts in HPV vaccination campaigns. Managing this condition involves a diverse team of healthcare professionals. Research in this field is undergoing a period of great revolution in multiple areas, and international guidelines will soon have to adapt to new scientific evidence. This could be true mainly in locally advanced stages, and it could also be true for minimal invasive surgery. This paper aims to summarize and compare the most recent recommendations published by international gynecological oncological societies for patients with cervical cancer. From their comparison, common aspects and disagreements emerged, especially in the diagnostic pathway and follow-up strategies. Several issues that remain to be debated in the literature were addressed and compared, highlighting similarities and differences, from the role of the sentinel lymph node in early stages to that of the adjuvant hysterectomy in locally advanced tumors. On the surgical side, for this last subset of patients, currently, a laparotomic approach is recommended. At the same time, the advent of immunotherapy has just opened up new and promising scenarios in systemic treatment for locally advanced cervical cancer, and international guidelines will soon introduce it into their algorithms. [ABSTRACT FROM AUTHOR]

A 43-year-old patient with a history of uterine fibromatosis was referred to our hospital for menometrorrhagia and pelvic pain. At the pelvic ultrasound, a highly-vascularized myometrial lesion in volumetric increase was described. An elongated, solid, hypoechoic, painless, and highly vascularized left parauterine mass was identified. On histological examination, a uterine smooth muscle tumor of uncertain malignant potential (STUMP) with intravascular invasion of the left uterine vein was diagnosed. The adnexa and peritoneum were free of disease. On a retrospective evaluation of the ultrasound images, we noticed that the intravascular lesion showed sonographic features comparable to the original mass. Moreover, the Color Doppler (CD) analysis revealed an interrupted blood flow within the left uterine vein. In this case, the ultrasound proved to be an accurate diagnostic tool. When inhomogeneous uterine masses are suspected, and a parauterine/paraadnexal mass surrounded by irregular vessels are identified, the sonographer should take into account a risk of intravascular invasion. The patency of uterine and ovarian vessels should be accurately evaluated, to guide a tailored patient surgical approach. [ABSTRACT FROM AUTHOR]

AbstractFoetal ductus arteriosus (DA) constriction can be found in complex foetal heart malformations, but rarely as an isolated defect. Although many cases of DA constriction are usually related to Non-steroidal Anti-Inflammatory Drugs (NSAIDs) maternal intake, other causes remain without an established aetiology and are referred to as idiopathic. Recently, a wide range of risks factors or substances (polyphenol-rich foods intake, naphazoline, fluoxetine, caffeine and pesticides) showed a definitive effect upon the pathway of inflammation, causing DA constriction. We report a case of a premature DA constriction in a woman whose possible risk factor was identified in her maternal occupational exposure to solvents and a comprehensive literature review of 176 cases of NSAID-unrelated DA constriction. A 30-year-old Asian woman was referred to our institution at 33 gestational weeks and 0 days because of suspicion of premature DA constriction. The woman had no history of medication intake, including NSAIDs, alcohol, tobacco or polyphenol-rich-food consumption during pregnancy. A detailed foetal echocardiography revealed a normal cardiac anatomy with hypertrophic, hypokinetic and a dilated right ventricle due to right pressure overload, holosystolic tricuspid regurgitation, and, at the level of the DA, high systolic and diastolic velocities, indicating premature ductal restriction. The right outflow showed dilatation of the pulmonary artery with narrow DA. An urgent caesarean section was performed at 33 gestational weeks and 4 days due to worsening of DA PI and signs of right pressure overload, despite the interruption of exposure to solvents. We assume a relationship exists between premature DA constriction and a maternal occupational exposure to solvents. This hypothesis is reinforced by the presence of associated foetal malformations in in two of the patient’s children. Further research is needed to confirm the role of exposure to solvents and toxic chemicals in the pathogenesis of DA constriction, also with experimental animal models.KEY MESSAGESMany cases of DA constriction are usually related to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) maternal intake.A wide range of risks factors or substances (polyphenol-rich foods intake, naphazoline, fluoxetine, caffeine and pesticides) can cause foetal DA constriction.Further investigation are needed to confirm the role of maternal exposure to solvents in the pathogenesis of DA constriction.

The appearance of severe vulvovaginal varicosities (VVs) is challenging in pregnancy. The management of VVs may require a multidisciplinary approach, including radiologists, vascular surgeons, and obstetricians. We report a rare case of enormous VVs and pubic varicosities and summarize similar cases in the literature. A woman in her 20s with a full-term pregnancy visited our hospital for severe VVs and pubic varicosities. She had been in a spoke maternity unit where a cesarean section was scheduled. After a multidisciplinary evaluation, we offered her the chance to have a vaginal delivery (VD). The woman had an uneventful VD, and VVs disappeared after 40 days. A comprehensive literature search on this topic showed 11 cases of VVs during pregnancy (five VDs and six cesarean sections). The presence of VVs represented the indication for surgery in 70% of cases. Severe complications occurred in 20% of VDs vs. 50% of CSs. In pregnant women with VVs, the risk-benefit ratio suggests a chance of having VD.