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Objectives: Currently available research data points to COVID-19-related multi-organ system damage. This study aims to evaluate the impact of SARS-CoV-2 on the reproductive health, that is, plasma levels of FSH, LH, estradiol, AMH, and antral follicular count, of women undergoing level II ART techniques. Methods: This is a multicenter, prospective, and observational study by the reproductive medicine centers of Palermo’s Ospedali Riuniti Villa Sofia-Cervello Hospital and Vanvitelli University. From September 2022 to March 2024, 203 patients aged 24–43 were enrolled, all with diagnosed infertility and a history of SARS-CoV-2 infection. Symptomatic women, patients testing positive for HIV or other liver viruses, and patients with a history of ovarian cancer or who had taken gonadotoxic drugs were excluded. Plasma measurements of FSH, LH, estradiol, AMH, and antral follicular count were performed before and after infection. Results: The analysis accounting for the concentration of anti-Müllerian hormone (AMH) before and after COVID-19 infection shows an average concentration decrease from 1.33 ng/mL before SARS-CoV-2 infection to 0.97 ng/mL after infection. Average decrease after infection was −27.4%; average reduction of 1 follicle (95% CI: from −0.74 to −1.33) was reported following SARS-CoV-2 infection. Levels of E2 before and after SARS-CoV-2 infection did not vary significantly. Average FSH and LH levels before and after SARS-CoV-2 infection pointed to an increase. Conclusions: SARS-CoV-2 infection damages female reproductive health, causing significant reductions in AMH (−27.4%) and AFC (−1 antral follicle) values and an increase in FSH (+13.6%) and LH (+13.4%) values. No effect on E2 levels was reported. The pandemic has also affected the ability of infertile patients to access ART procedures, and that calls for a novel, updated blueprint designed to enhance our preparedness in the event that similar circumstances should occur again.

Ovarian cancer represents the fifth cause of cancer death among women, carrying one of the worst prognoses among gynaecological malignancies. The need to achieve no residual disease after surgery in order to optimize prognosis of advanced-stage ovarian cancer introduced the idea of neoadjuvant chemotherapy. The present review aims to summarize current state-of-the-art evidence regarding the efficacy and safety of neoadjuvant chemotherapy as well as novel insights regarding the usage of modern therapeutic regimens in the context of neoadjuvant chemotherapy. The last decade has been characterized by the breakthrough scientific evidence that neoadjuvant chemotherapy followed by interval debulking surgery for advanced-stage ovarian cancer may be comparable to primary debulking surgery. Neoadjuvant chemotherapy followed by interval debulking surgery is an acceptable – if not preferable – therapeutic approach in advanced-staged ovarian cancer patients because it is associated with higher optimal debulking surgery, fewer complications, and non-inferior survival outcomes. The addition of bevacizumab to chemotherapy contributes significantly to survival outcomes without causing side effects that outbalance the benefits. Patients with recurrent high-grade serous ovarian cancer and a germline or breast cancer mutation should be offered maintenance olaparib after a response to platinum-based chemotherapy. Finally, the role of hyperthermic intraperitoneal chemotherapy in the context of neoadjuvant chemotherapy remains unjustified.

Utero-cutaneous fistula is an extremely rare condition characterized by an abnormal communication between the anterior wall of the uterus and the abdominal wall. The causes include multiple caesarean sections, incomplete hysterorrhaphy, miscarriages, uterine cavity revision, retention of placental material after delivery, use of drains, post-operative infections, or injuries. Herein, we report a case of a 38-year-old female, who underwent caesarean section 42 days earlier and presented to the emergency room complaining of fever, abdominal pain, and purulent discharge from the abdominal wall from 6 days. Her medical history included 2 previous term caesarean section deliveries and an hysteroscopic polypectomy 2 years earlier. A pelvic computed tomography scan with contrast medium showed fluid/super-fluid phlogistic collection reported at the anterior wall of the uterus with a continuous solution of the uterine wall itself. Magnetic resonance imaging demonstrated the presence of a probable hyperintense fistula, extended for 30 mm and 16 mm of thickness, which ended in the subcutaneous area with an abscess joint without continuous solution with the skin. A laparotomic surgical procedure was successfully performed. Histopathology confirmed the surgical suspect of utero-cutaneous fistula. Although utero-cutaneous fistula is an extremely rare complication, it should be considered if after caesarean section delivery signs and symptoms of skin inflammation and/or infection persist.

Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to tumor development and angiogenesis in different types of cancer. Recently, complex interactions among coding and non-coding RNA have been elucidated, further shedding light on the complexity of the roles these molecules fulfill in cancer formation. In this context, knowledge about the role of miR in BC has significantly improved, highlighting the deregulation of these molecules as additional factors influencing BC occurrence, development and classification. A considerable number of papers has been published over the past few years regarding the role of miR-125 in human pathology in general and in several types of cancer formation in particular. Interestingly, miR-125 family members have been recently linked to BC formation as well, and complex interactions (competing endogenous RNA networks, or ceRNET) between this molecule and target mRNA have been described. In this review, we summarize the state-of-the-art about research on this topic.

(1) Background: The peripherally inserted central catheter (PICC) is commonly used in medicine. The tip position was shown to be a major determinant in PICC function and related complications. Recent advances in ECG guidance might facilitate daily practice. This study aimed to compare two ECG techniques, in terms of their tip-position accuracy, puncture site layout, and signal quality; (2) Methods: This randomized open study (1:1) included 320 participants. One PICC guidance technique used ECG signal transmission with saline (ST); the other technique used a guidewire (WT). Techniques were compared by the distance between the catheter tip and the cavoatrial junction (DCAJ) on chest X-rays, insertion-point hemostasis time, and the extracorporeal catheter length between the hub and the insertion point; (3) Results: The mean DCAJs were significantly different between ST (1.36 cm, 95% CI: 1.22–1.37) and WT (1.12 cm, 95% CI: 0.98–1.25; p = 0.013) groups. When DCAJs were classified as optimal, suboptimal, or inadequate, the difference between techniques had limited clinical impact (p = 0.085). However, the hemostasis time at the puncture site was significantly better with WT (no delay in 82% of patients) compared to ST (no delay in 50% of patients; p < 0.001). Conversely, ST achieved optimal and suboptimal extracorporeal lengths significantly more frequently than WT (100% vs. 66%; p < 0.001); (4) Conclusions: ECG guidance technologies achieved significantly different tip placements, but the difference had minimal clinical impact. Nevertheless, each technique displayed an important drawback at the PICC insertion point: the extracorporeal catheter was significantly longer with WT and the hemostasis delay was significantly longer with ST.

ObjectivesIn randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression.MethodsPatients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring).ResultsIn the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction—the most suitable method based on published guidelines and trial characteristics—produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction.ConclusionsAfter adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.

Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and mono-saccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and well-designed randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.

Background: Coronary CT angiography (CCTA) is increasingly used as a non-invasive tool to assess coronary artery disease (CAD). However, CCTA is subject to motion artifacts, potentially limiting its clinical utility. Despite faster (0.35 and 0.28 s/rot) gantry rotation times, low (60–65 bpm) heartbeat is recommended, and the use of β-blockers is often needed. Technological advancements have resulted in the development of faster rotation speeds (0.23 s/rot). However, their added value in patients not premedicated with β-blockers remains unclear. This prospective single-center, two-arm, randomized, controlled trial aims to assess the influence of fast rotation on coronary motion artifacts, diagnostic accuracy of CCTA for CAD, and patient safety. Methods: We will randomize a total of 142 patients aged ≥ 50 scheduled for an aortic stenosis work-up to receive CCTA with either a fast (0.23) or standard (0.28 s/rot) gantry speed. Primary outcome: rate of CCTAs with coronary motion artifacts hindering interpretation. Secondary outcomes: assessable coronary segments rate, diagnostic accuracy against invasive coronary angiography (ICA), motion artifact magnitude per segment, contrast-to-noise ratio (CNR), and patient ionizing radiation dose. The local ethics committee has approved the protocol. Potential significance: FAST-CCT may improve motion artifact reduction and diagnosis quality, thus eliminating the need for rate control and β-blocker administration. Clinicaltrials.gov identifier: NCT05709652.

Heterotopic pregnancy is a rare but intriguing disease, which poses a high risk for pregnant women and for intrauterine pregnancy. Clinically, it is mainly characterized by pain and vaginal bleeding. b-hCG serum dosage is used to detect the pregnancy, but transvaginal ultrasound is needed to diagnose heterotopic pregnancy. From all the risk factors, the assisted reproductive treatments represent the most important, especially when multiple embryos are transferred. Patients with a heterotopic pregnancy are at risk of having a spontaneous or medically induced abortion, and for this reason appropriate and tailored treatment should be considered, pursuing the optimal risk/benefit ratio. Although conservative treatments are available in the case of only extrauterine pregnancy, such as methotrexate, often the laparoscopic approach seems unavoidable in heterotopic pregnancy. To preserve the intrauterine pregnancy, a conservative treatment is remarkable, both salpingotomy or salpingostomy. In this case report, we present a successful laparoscopic treatment of an extrauterine pregnancy with the prosecution of the intrauterine pregnancy up to the third trimester. In particular, a 25-year-old girl referred to the Villa Sofia Cervello Hospital complaining of abdominopelvic pain and vaginal bleeding for 2 days. The salpingectomy approach was performed, and every anatomical piece was sent for histopathology.

Objective: The scientific community has recently directed its attention towards investigating the role of androgens in female sexuality. This narrative review aims to elucidate the central and peripheral androgen-mediated mechanisms involved in female sexual health and function. Additionally, the current state of androgen therapeutic options is discussed. Mechanism: We searched several scientific literature databases, including EMBASE, MEDLINE, PubMed Central, and Scopus, utilizing keywords, index terms, and MeSH terms, such as “androgen*”, “female sexuality”, “female sexual function”, “women’s sexual dysfunctions”, “androgen therapy in women”, and various combinations thereof. Findings in Brief: Progesterone or estrogens are commonly prescribed as first-line treatments for female sexual dysfunctions. However, these medications may frequently lead to therapeutic failure and cause harm by increasing sex-hormone-binding-globulin plasma levels and decreasing testosterone plasma concentrations. Currently, there are limited androgen therapies available for women, and the evidence for their effectiveness and safety is still limited. Conclusions: The knowledge of neuroendocrine interactions that underlie sexual arousal and pleasure is rapidly expanding, and ongoing research is striving to develop more appropriate clinical practices for managing sexual dysfunctions in women.

Background: For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published from January 2010 to November 2020. Methods: Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50–0.86), 1–12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04–2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54–1.10), 1–12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3–5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83–2.60)], immune-mediated AEs [1.75 (0.33–7.49)], and all-cause discontinuation due to AEs [1.21 (0.58–2.61)]. Conclusions: Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

Abstract To verify whether myo-inositol plus α-lactalbumin may reduce insulin resistance and excessive fetal growth in women with gestational diabetes mellitus. In a 12-month period, 120 women with a diagnosis of gestational diabetes mellitus were consecutively enrolled with an allocation of 1:1 in each group and randomly treated with myo-inositol plus α-lactalbumin plus folic acid (treated group) or folic acid (control group) for 2 months. Primary outcome was the variation of insulin resistance through the study evaluated by HOMA-IR. Secondary outcome was the evaluation, through the study, of fetal growth by ultrasound measurements of abdominal circumference centiles and estimated fat thickness. Some clinical outcomes were also considered. After 2 months, in the treated group, a significant reduction in insulin resistance (HOMA values 3.1 ± 1.4 vs 6.1 ± 3.4, p = 0.0002) and fetal growth was shown (Abdominal circumference centiles 54.9 ± 23.5 vs 67.5 ± 22.6, P = 0.006). Among clinical outcomes, a significant decrease in the rate of women who needed insulin (6.7% vs 20.3%, p = 0.03) and of pre-term birth (0 vs 15.2%, p = 0.007) was evidenced. A combination of myo-inositol and α-lactalbumin may reduce insulin resistance and excessive fetal growth. Clinical trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov , NCT 03763669, first posted date 04/12/2018; last posted date December 06/12/2018.

Pregnancy does not appear to increase susceptibility to SARS-CoV-2 infection, but some physiological changes, such as the reduction of residual functional volumes, elevation of the diaphragm, and impaired cellular immunity, may increase the risk of severe disease and result in a higher risk of complications. The article’s primary objective is to evaluate the factors associated with symptomatic COVID-19 disease in pregnancy. The secondary objective is to describe maternal and neonatal outcomes and cases of vertical transmission of the infection. All pregnant women hospitalized with SARS-CoV2 infection were included in a prospective study in the UOC of Obstetrics and Gynecology, AOOR Villa Sofia—Cervello, Palermo, between May 2020 and April 2021. The patients who requested the termination of the pregnancy according to Law 194/78 were excluded. We included 165 pregnancies with a total number of 134 deliveries. Overall, 88.5% of the patients were asymptomatic at the time of admission and 11.5% were symptomatic. Of them, 1.8% of the patients required hospital admission in the intensive care unit. Symptoms occurrences were positively associated with the increase in maternal BMI (OR 1.17; p = 0.002), the prematurity (OR 4.71; p = 0.022), and at a lower birth weight (OR 0.99; p = 0.007). One infant tested positive for SARS-CoV2 nasopharyngeal swab; 11.4% of newborns had IgG anti SARS-CoV2 at birth; IgM was positive in 2.4% of newborns. There was no difference statistically significant difference in the vertical transmission of the infection among the group of symptomatic pregnant women and that of asymptomatic pregnant women.

Intracavitary electrocardiography is an accurate guidance technique for peripherally inserted central catheters (PICC) tip location that is spreading widely among providers using non x-ray-based facilities. The principle behind this technology relies on the transmission of the electrocardiographic signal at the tip of the catheter and its use as an internal mobile electrode, allowing the system to identify the cavo-atrial junction (CAJ) through internal P-wave amplitude modulations. The gain in popularity of intracavitary electrography and its large diffusion have led manufacturers to offer various devices with heterogeneous properties, among which clinician who place PICCs have to choose. It is therefore important to understand differences between available techniques and devices. The potential impact might not only affect availability and costs but also the clinical impact through advantages and limitations regarding electric signal transmission PICC selection. Current perspectives on intracavitary electrocardiography will also be discussed, to give the reader a global view of the management of electrocardiographically guided PICCs, especially in an environment without x-ray support.

IntroductionKlippel–Trenaunay syndrome (KTS) is a rare vascular congenital disorder characterized by the classical triad of port-wine stains, abnormal growth of soft tissues and bones, and vascular malformations. The involvement of the genitourinary tract and of the uterus in particular is extremely infrequent but relevant for possible consequences.MethodsWe performed an extensive review of the literature using the Pubmed, Scopus and ISI web of knowledge database to identify all cases of KTS with uterine involvement. The search was done using the MeSH term “Klippel–Trenaunay syndrome” AND “uterine” OR “uterus.” We considered publications only in the English language with no limits of time. We selected a total of 11 records of KTS with uterine involvement, including those affecting pregnant women.ResultsKlippel–Trenaunay syndrome was described for the first time in the year 1900 in two patients with hemangiomatous lesions of the skin associated with varicose veins and asymmetric soft tissue and bone hypertrophy. Uterine involvement is a rare condition and can cause severe menorrhagia. Diagnosis is based on physical signs and symptoms. CT scans and MRI are first-choice test procedures to evaluate both the extension of the lesion and the infiltration of deeper tissues before treatment. The management of Klippel–Trenaunay syndrome should be personalized using careful diagnosis, prevention and treatment of complications.ConclusionKlippel–Trenaunay syndrome is a rare vascular malformation with a wide variability of manifestations. There are no univocal and clear guidelines that suggest the most adequate monitoring of the possible complications of the disease. Treatment is generally conservative, but in case of recurrent bleeding, surgery may be needed.

Endovascular interventions (EVI) are increasingly performed as minimally-invasive alternatives to surgery and have many advantages, including a decreased need for general anesthesia. However, EVI can be stressful for patients and often lead to anxiety and pain related to the procedure. The use of local anesthetics, anxiolytics, and analgesic drugs can help avoid general anesthesia. Nevertheless, these drugs have potential side effects. Alternative nonpharmacological therapies can improve patients’ experience during conscious interventions and reduce the need for additional medications. The added value of virtually augmented self-hypnosis (VA-HYPO) and its potential to reduce pain and anxiety during peripheral and visceral arterial and venous EVI is unknown. This is a prospective two-arm trial designed to randomize 100 patients in two groups according to the use or not of VA-HYPO during peripheral EVI as a complementary nonpharmacological technique to improve patient comfort. The main objective is to compare per-procedural anxiety, and the secondary aim is to compare the rated per-procedural pain in both groups. The potential significance is that VA-HYPO may improve patients’ experience during peripheral and visceral arterial and venous EVI and other minimally invasive interventions performed under local anesthesia. Trial registration: Our study is registered on clinicaltrials.gov, with trial registration number: NCT04561596.

There is a rising incidence of infertility worldwide, and many couples experience difficulties conceiving nowadays. Thyroid autoimmunity (TAI) is recognized as one of the major female infertility causes related to a diminished ovarian reserve and potentially impaired oocyte maturation and embryo development, causing adverse pregnancy outcomes. Growing evidence has highlighted its impact on spontaneously achieved pregnancy and pregnancy achieved by in vitro fertilization. Despite the influence of thyroid hormones on the male reproductive system, there is insufficient data on the association between TAI and male infertility. In past years, significant progress has been achieved in cell and gene therapies as emerging treatment options for infertility. Cell therapies utilize living cells to restore healthy tissue microenvironment and homeostasis and usually involve platelet-rich plasma and various stem cells. Using stem cells as therapeutic agents has many advantages, including simple sampling, abundant sources, poor immunogenicity, and elimination of ethical concerns. Mesenchymal Stem Cells (MSCs) represent a heterogeneous fraction of self-renewal, multipotent non-hematopoietic stem cells that display profound immunomodulatory and immunosuppressive features and promising therapeutic effects. Infertility has a genetic component in about half of all cases, although most of its genetic causes are still unknown. Hence, it is essential to identify genes involved in meiosis, DNA repair, ovarian development, steroidogenesis, and folliculogenesis, as well as those involved in spermatogenesis in order to develop potential gene therapies for infertility. Despite advances in therapy approaches such as biological agents, autoimmune disorders remain impossible to cure. Recent research demonstrates the remarkable therapeutic effectiveness of MSCs in a wide array of autoimmune diseases. TAI is one of many autoimmune disorders that can benefit from the use of MSCs, which can be derived from bone marrow and adipose tissue. Cell and gene therapies hold great potential for treating autoimmune conditions, although further research is still needed.

Pregnant women are at higher risk of severe Coronavirus disease 2019 (COVID-19) complications than non-pregnant women. The initial exclusion of pregnant women from anti-SARS-CoV-2 vaccines clinical trials has caused a lack of conclusive data about safety and efficacy for this vulnerable population. This cross-sectional study aims to define the factors related to vaccination adherence in a sample of women experiencing high-risk pregnancies. The recruited women completed a questionnaire based on the Health Belief Model. Data were analyzed to evaluate the associations between socio-demographic variables and vaccination acceptance through descriptive, univariate and multivariate logistic analyses. Among the 233 women enrolled, 65.2% (n = 152) declared that they would accept the anti-SARS-CoV-2 vaccine. Multivariate analysis showed that vaccination acceptance was associated with a high educational level (aOR = 4.52, p = 0.001), a low perception of barriers to vaccination (aOR = 1.58, p = 0.005) and the gynecologist’s advice (aOR = 3.18, p = 0.01). About a third of pregnant women are still hesitant about the anti-SARS-CoV-2 vaccine, probably because of the conflicting information received from media, friends, acquaintances and health institutions. Determining factors linked to vaccine hesitancy among pregnant women is useful for creating vaccination strategies that increase vaccination uptake.

BackgroundTeaching medical ultrasound has increased in popularity in medical schools with hands-on workshops as an essential part of teaching. However, the lockdown due to COVID-19 kept medical schools from conducting these workshops. ObjectiveThe aim of this paper is to describe an alternative method used by our medical school to allow our students to acquire the essential psychomotor skills to produce ultrasound images. MethodsOur students took online ultrasound courses. Consequently, they had to practice ultrasound exercises on a virtual simulator, using the mouse of their computer to control a simulated transducer. Our team measured the precision reached at the completion of simulation exercises. Before and after completion of the courses and simulator’s exercises, students had to complete a questionnaire dedicated to psychomotor skills. A general evaluation questionnaire was also submitted. ResultsA total of 193 students returned the precourse questionnaire. A total of 184 performed all the simulator exercises and 181 answered the postcourse questionnaire. Of the 180 general evaluation questionnaires that were sent out, 136 (76%) were returned. The average precourse score was 4.23 (SD 2.14). After exercising, the average postcourse score was 6.36 (SD 1.82), with a significant improvement (P

Infertility is a global health issue affecting women and men of reproductive age with increasing incidence worldwide, in part due to greater awareness and better diagnosis. Assisted reproduction technologies (ART) are considered the ultimate step in the treatment of infertility. Recently, artificial intelligence (AI) has been progressively used in the many fields of medicine, integrating knowledge and computer science through machine learning algorithms. AI has the potential to improve infertility diagnosis and ART outcomes estimated as pregnancy and/or live birth rate, especially with recurrent ART failure. A broad-ranging review has been conducted, focusing on clinical AI applications up until September 2022, which could be estimated in terms of possible applications, such as ultrasound monitoring of folliculogenesis, endometrial receptivity, embryo selection based on quality and viability, and prediction of post implantation embryo development, in order to eliminate potential contributing risk factors. Oocyte morphology assessment is highly relevant in terms of successful fertilization rate, as well as during oocyte freezing for fertility preservation, and substantially valuable in oocyte donation cycles. AI has great implications in the assessment of male infertility, with computerised semen analysis systems already in use and a broad spectrum of possible AI-based applications in environmental and lifestyle evaluation to predict semen quality. In addition, considerable progress has been made in terms of harnessing AI in cases of idiopathic infertility, to improve the stratification of infertile/fertile couples based on their biological and clinical signatures. With AI as a very powerful tool of the future, our review is meant to summarise current AI applications and investigations in contemporary reproduction medicine, mainly focusing on the nonsurgical aspects of it; in addition, the authors have briefly explored the frames of reference and guiding principles for the definition and implementation of legal, regulatory, and ethical standards for AI in healthcare.

In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.

Molecular and histopathological analysis of melanoma subtypes has revealed distinct epidemiological, genetic, and clinical features. However, immunotherapy for advanced metastatic melanoma patients does not differ based on subtype. Response to immune checkpoint inhibitors (ICI) has been shown to vary, therefore, predictive biomarkers are needed in the design of precision treatments. Targeted sequencing and histopathological analysis (CD8 and CD20 immunohistochemistry) were performed on subtypes of metastatic melanoma (cutaneous melanoma (CM, n = 10); head and neck melanoma (HNM, n = 7); uveal melanoma (UM, n = 4); acral lentiginous melanoma (AM, n = 1) and mucosal melanoma (MM, n = 1) treated with ICI). Progression-free survival (PFS) was significantly associated with high CD8 expression (p = 0.025) and mutations in DNA damage repair (DDR) pathway genes (p = 0.012) in all subtypes but not with CD20 expression. Our study identified that immune cell infiltration and DDR gene mutations may have an impact in response to ICI treatment in metastatic melanoma but differs among subtypes. Therefore, a comprehensive understanding of the immune infiltration cells’ role and DDR gene mutations in metastatic melanoma may identify prognostic biomarkers.

Background: Cystic Fibrosis (CF) is a genetic disease which is responsible for different systemic conditions. In particular, CF could be responsible for infertility, especially in the male partner due to congenital bilateral absence of vas deferens (CBAVD). Moreover, in Assisted Reproductive Techniques CF screening is performed in order to detect possible risks for the newborn. For this reason, CF testing is one of the main genetic screening performed in infertile couples. Methods: In this scenario, we present a prospective observational study in CF testing with Next Generation Sequencing (NGS) technique on 360 subjects referring to an In-Vitro Fertilization center. Results: 360 subjects were screened for CFTR. Of them, 19 subjects presented CF causing variants, 44 subjects presented CFTR-RD associated, 22 subjects had variants of uncertain significance and 19 subjects with no clinical consequences. Conclusion: Results clarify proportions of the main CF mutations. Actually, there are no more advanced techniques rather than Next Generation Sequencing (NGS) technique, although it is not yet widely used as a test for the identification of the CF carrier.

Background: Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients. Methods: Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m 2 ). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF). Results: A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1–72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12–54) months in TN patients versus 38 (22–71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity. Conclusions: We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further. Trial Registration ClinicalTrials.gov Identifier: NCT00911716.

Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.