Detection and Classification of Hysteroscopic Images Using Deep Learning.

BACKGROUND: Although hysteroscopy with endometrial biopsy is the gold standard in the diagnosis of endometrial pathology, the gynecologist experience is crucial for a correct diagnosis. Deep learning (DL), as an artificial intelligence method, might help to overcome this limitation. Unfortunately, only preliminary findings are available, with the absence of studies evaluating the performance of DL models in identifying intrauterine lesions and the possible aid related to the inclusion of clinical factors in the model. AIM: To develop a DL model as an automated tool for detecting and classifying endometrial pathologies from hysteroscopic images. METHODS: A monocentric observational retrospective cohort study was performed by reviewing clinical records, electronic databases, and stored videos of hysteroscopies from consecutive patients with pathologically confirmed intrauterine lesions at our Center from January 2021 to May 2021. Retrieved hysteroscopic images were used to build a DL model for the classification and identification of intracavitary uterine lesions with or without the aid of clinical factors. Study outcomes were DL model diagnostic metrics in the classification and identification of intracavitary uterine lesions with and without the aid of clinical factors. RESULTS: We reviewed 1500 images from 266 patients: 186 patients had benign focal lesions, 25 benign diffuse lesions, and 55 preneoplastic/neoplastic lesions. For both the classification and identification tasks, the best performance was achieved with the aid of clinical factors, with an overall precision of 80.11%, recall of 80.11%, specificity of 90.06%, F1 score of 80.11%, and accuracy of 86.74 for the classification task, and overall detection of 85.82%, precision of 93.12%, recall of 91.63%, and an F1 score of 92.37% for the identification task. CONCLUSION: Our DL model achieved a low diagnostic performance in the detection and classification of intracavitary uterine lesions from hysteroscopic images. Although the best diagnostic performance was obtained with the aid of clinical data, such an improvement was slight.

Possible Effect of Polycystic Ovary Syndrome (PCOS) on Cardiovascular Disease (CVD): An Update.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during the fertile period. Women with PCOS have an increased risk of developing major cardiovascular risk factors during the fertile period: obesity, impaired glucose tolerance, diabetes mellitus, dyslipidemia, and metabolic syndrome. The possible effect of PCOS on cardiovascular disease (CVD) has been reported in different studies, but the results are not clear for several reasons. Indeed, most of the studies analyzed a cohort of fertile women who, given their relatively young age, have a low frequency of cardiovascular diseases. In addition, longitudinal studies have a short follow-up period, insufficient to draw firm conclusions on this topic. Finally, pharmacological treatment is limited by the lack of specific drugs available to specifically treat PCOS. In this review, we report on studies that analyzed the possible effect of PCOS on the most common CVD (hypertension, arterial stiffness, atherosclerosis, and cardiovascular event) and available drugs used to reduce CVD in PCOS women.

Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study.

Background: The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. Methods: We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. Results: IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Conclusion: Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. Declaration: This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.

HPV-related lesions after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer: A focus on the potential role of vaccination.

OBJECTIVE: To date, no data supports the execution of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia (CIN2+) and early-stage cervical cancer. We aim to evaluate the potential effect of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer. METHODS: This is a multi-center retrospective study evaluating data of women who develop lower genital tract dysplasia (including anal, vulvar and vaginal intra-epithelial neoplasia) after having hysterectomy for CIN2+ and FIGO stage IA1- IB1 cervical cancer. RESULTS: Overall, charts for 77 patients who developed lower genital tract dysplasia were collected. The study population included 62 (80.5%) and 15 (19.5%) patients with CIN2+ and early-stage cervical cancer, respectively. The median (range) time between hysterectomy and diagnosis of develop lower genital tract dysplasia was 38 (range, 14-62) months. HPV types covered by the nonavalent HPV vaccination would potentially cover 94.8% of the development of lower genital tract dysplasia. Restricting the analysis to the 18 patients with available HPV data at the time of hysterectomy, the beneficial effect of nonvalent vaccination was 89%. However, considering that patients with persistent HPV types (with the same HPV types at the time of hysterectomy and who developed lower genital tract dysplasia) would not benefit from vaccination, we estimated the potential protective effect of vaccination to be 67% (12 out of 18 patients; four patients had a persistent infection for the same HPV type(s)). CONCLUSIONS: Our retrospective analysis supported the adoption of HPV vaccination in patients having treatment for HPV-related disease. Even in the absence of the uterine cervix, HPV vaccination would protect against develop lower genital tract dysplasia. Further prospective studies have to confirm our preliminary research.

Stratification of Amniotic Fluid Cells and Amniotic Fluid by Sex Opens Up New Perspectives on Fetal Health.

Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life, but knowledge of its influence on cell-depleted amniotic fluid (AF) and amniotic fluid cells (AFCs) is still neglected. We evaluated sex-related differences in AF and in AFCs to extend personalized medicine to prenatal life. AFCs and AF were obtained from healthy Caucasian pregnant women who underwent amniocentesis at the 16th-18th week of gestation for advanced maternal age. In the AF, inflammation biomarkers (TNFα, IL6, IL8, and IL4), malondialdehyde, nitrites, amino acids, and acylcarnitines were measured. Estrogen receptors and cell fate (autophagy, apoptosis, senescence) were measured in AFCs. TNFα, IL8, and IL4 were higher in female AF, whereas IL6, nitrites, and MDA were similar. Valine was higher in male AF, whereas several acylcarnitines were sexually different, suggesting a mitochondrial involvement in establishing sex differences. Female AFCs displayed higher expression of ERα protein and a higher ERα/ERß ratio. The ratio of LC3II/I, an index of autophagy, was higher in female AFCs, while LC3 gene was similar in both sexes. No significant sex differences were found in the expression of the lysosomal protein LAMP1, while p62 was higher in male AFCs. LAMP1 gene was upregulated in male AFCs, while p62 gene was upregulated in female ones. Finally, caspase 9 activity and senescence linked to telomeres were higher in female AFCs, while caspase 3 and ß-galactosidase activities were similar. This study supports the idea that sex differences start very early in prenatal life and influence specific parameters, suggesting that it may be relevant to appreciate sex differences to cover knowledge gaps. This might lead to improving the diagnosis of risk prediction for pregnancy complications and achieving a more satisfactory monitoring of fetus health, even preventing future diseases in adulthood.

Sex Influence on Autophagy Markers and miRNAs in Basal and Angiotensin II-Treated Human Umbilical Vein Endothelial Cells.

Cardiovascular diseases (CVD) display many sex and gender differences, and endothelial dysfunction, angiotensin II (Ang II), and autophagy represent key factors in the autophagic process Therefore, we studied whether Ang II modulates the mentioned processes in a sex-specific way in HUVECs obtained from healthy male and female newborns. In basal HUVECs, the Parkin gene and protein were higher in FHUVECs than in MHUVECs, while the Beclin-1 protein was more expressed in MHUVECs, and no other significant differences were detected. Ang II significantly increases LAMP-1 and p62 protein expression and decreases the expression of Parkin protein in comparison to basal in MHUVECs. In FHUVECs, Ang II significantly increases the expression of Beclin-1 gene and protein, and Parkin gene. The LC3 II/I ratio and LAMP-1 protein were significantly higher in MHUVECs than in FHUVECs, while Parkin protein was significantly more expressed in Ang II-treated FHUVECs than in male cells. Ang II affects the single miRNA levels: miR-126-3p and miR-133a-3p are downregulated and upregulated in MHUVECs and FHUVECs, respectively. MiR-223 is downregulated in MHUVEC and FHUVECs. Finally, miR-29b-3p and miR-133b are not affected by Ang II. Ang II effects and the relationship between miRNAs and organelles-specific autophagy is sex-dependent in HUVECs. This could lead to a better understanding of the mechanisms underlying sex differences in endothelial dysfunction, providing useful indications for innovative biomarkers and personalized therapeutic approaches.

What is the impact of stress on the onset and anti-thyroid drug therapy in patients with graves' disease: a systematic review and meta-analysis.

BACKGROUND: The effect of stress on Graves' disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves' disease. METHODS: Systematic searches of PubMed, MEDLINE, Embase, Web of Science, Scopus, Cochrane Library and PsycInfo were conducted from inception to 1 January 2023. Studies comparing the incidence of stressful life events (SLEs) that occurred before diagnosis and during drug therapy in cases diagnosed with GD and controls were included in the final analysis. RESULTS: Nine case-control studies and four cohort studies enrolling 2892 participants (1685 [58%] patients) were included. Meta-analysis revealed a high and significant effect-size index in a random effect model (d = 1.81, P = 0.01), indicating that stress is an important factor in the onset of GD. The relationship between SLEs and GD was stronger in studies with higher proportions of female patients (ß = 0.22, P < 0.01) and weaker in studies with older patients with GD (ß =-0.62, P < 0.01). However, stress did not significantly affect the outcome of antithyroid drug therapy for GD (d = 0.32, P = 0.09). CONCLUSIONS: The results of this meta-analysis suggest that stress is one of the environmental triggers for the onset of GD. Therefore, we recommend stress management assistance for individuals genetically susceptible to GD, especially for young females.

Intrahepatic cholestasis of pregnancy after ovarian hyperstimulation syndrome with wild-type ABCB4 gene: a peculiar case and literature review.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) in the first trimester occurring after ovarian hyperstimulation syndrome (OHSS) is a rare condition and few cases are reported in the literature. Hyperestrogenism may explain this problem in genetically predisposed women. The objective of this article is to report one of these rare cases and offer an overview of the other published cases. CASE PRESENTATION: We report a case of severe OHSS followed by ICP in the first trimester. The patient was admitted to the intensive care unit and was treated according to the guidelines for the management of OHSS. Moreover, the patient also received ursodeoxycholic acid for ICP, which brought to an improvement of her clinical conditions. The pregnancy continued without other complications until the 36th week of gestation, when the patient developed ICP in the third trimester and underwent cesarean section for increased bile acid levels and cardiotocographic (CTG) pathologic alterations. The newborn was a healthy baby weighing 2500 gr. We also reviewed other case reports published by other authors about this clinical condition. We present what is, to our knowledge, the first case of ICP developed in the first trimester of pregnancy after OHSS in which genetic polymorphisms of ABCB4 (MDR3) have been investigated. CONCLUSIONS: ICP in the first trimester might be induced by elevated serum estrogen levels after OHSS in genetically predisposed women. In these women, it might be useful to check for genetic polymorphisms to know if they have a predisposition for ICP recurrence in the third trimester of pregnancy.

Ten-year outcomes following laparoscopic and open abdominal radical hysterectomy for "low-risk" early-stage cervical cancer: A propensity-score based analysis.

OBJECTIVE: Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. METHODS: This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. RESULTS: Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100-310) vs. 184 (range, 150-240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100-1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). CONCLUSIONS: Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients.

Mesenchymal Stem Cell Behavior under Microgravity: From Stress Response to a Premature Senescence.

Mesenchymal stem cells are undifferentiated cells able to acquire different phenotypes under specific stimuli. Wharton's jelly is a tissue in the umbilical cord that contains mesenchymal stromal cells (MSCs) with a high plasticity and differentiation potential. Their regeneration capability is compromised by cell damage and aging. The main cause of cell damage is oxidative stress coming from an imbalance between oxidant and antioxidant species. Microgravity represents a stressing condition able to induce ROS production, ultimately leading to different subcellular compartment damages. Here, we analyzed molecular programs of stemness (Oct-4; SOX2; Nanog), cell senescence, p19, p21 (WAF1/CIP1), p53, and stress response in WJ-MSCs exposed to microgravity. From our results, we can infer that a simulated microgravity environment is able to influence WJ-MSC behavior by modulating the expression of stress and stemness-related genes, cell proliferation regulators, and both proapoptotic and antiapoptotic genes. Our results suggest a cellular adaptation addressed to survival occurring during the first hours of simulated microgravity, followed by a loss of stemness and proliferation capability, probably related to the appearance of a molecular program of senescence.

Membranous dysmenorrhoea in a woman undergoing hormone replacement preparation for embryo transfer - a peculiar case.

Membranous dysmenorrhoea is an uncommon condition characterized by the spontaneous flaking of endometrium into a single piece that maintains the shape of the uterus. The common symptom of membranous dysmenorrhoea is a colicky pain caused by uterine contractions. Because only a limited number of cases have been published in the literature, the case report we present is peculiar. This report describes a case of membranous dysmenorrhoea that occurred after an artificial frozen thawed embryo transfer cycle using vaginal progesterone. The patient, during hormone replacement treatment, reported an intense abdominal colicky pain resulting in the loss of membranous endometrial tissue. A histopathological exam was performed with a clear diagnosis of membranous dysmenorrhoea. Moreover, photos were recorded and provided together with this article. The importance of such a case report relies on the actual debate about the appropriate progesterone route of administration. Although different medical approaches exist, progesterone administration is the most widespread. However, the intramuscular, oral, and subcutaneous means of administration are gaining popularity. On this peculiar case report, the patient underwent a subsequent frozen thawed embryo transfer cycle with subcutaneous progesterone administration. The embryo transfer resulted first in a clinical pregnancy and subsequently in a spontaneous delivery without any complications.

Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization.

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.

Current Trends in Mucosal Melanomas: An Overview.

Primary mucosal melanomas (MMs) are uncommon tumors originating from melanocytes located in the mucous membranes at various anatomic sites within the body. MM significantly differs from cutaneous melanoma (CM) regarding epidemiology, genetic profile, clinical presentation, and response to therapies. Despite these differences, that have important implications for both disease diagnosis and prognosis, MMs are usually treated in the same way as CM but exhibit a lower response rate to immunotherapy leading to a poorer survival rate. Furthermore, a high inter-patient variability can be observed in relation to therapeutic response. Recently, novel "omics" techniques have evidenced that MM lesions have different genomic, molecular, and metabolic landscapes as compared with CM lesions, thus explaining the heterogeneity of the response. Such specific molecular aspects might be useful to identify new biomarkers aimed at improving the diagnosis and selection of MM patients who could benefit from immunotherapy or targeted therapy. In this review, we have focused on relevant molecular and clinical advancements for the different MM subtypes in order to describe the updated knowledge relating to main diagnostic, clinical, and therapeutic implications as well as to provide hints on likely future directions.

Telemedicine for Virtual Consultations During COVID-19 Pandemic in a Medically Assisted Reproduction Center: Patients' Perspective.

Background: Restrictive measures imposed to prevent COVID-19 contagion have caused an increase in waiting times for other health procedures. During the pandemic, utilization of telemedicine has increased to ensure patient care safely. The aim of this study was to evaluate the perspective of infertile patients who underwent virtual consultations for infertility. Materials and Methods: This was an observational study. A survey was submitted to patients who attended a virtual consultation at a single in vitro fertilization (IVF) unit between March 2020 and July 2021. The survey concerned their experience with telemedicine assessing the experience of video consulting and the software characteristics. Results: The survey response rate was 50.3% (n = 159). In total, 98.8% of patients positively rated the experience of telemedicine. Regarding the software itself, it was defined as intuitive and easy to use by 87.4% of patients. A majority (92.5%) of interviewed patients reported that they were able to receive the information and clear any doubts they had and 85.5% of interviewed patients would repeat the experience of video consultation. Conclusions: The acceptance of telemedicine was very high among infertile patients. However, IVF treatments have a strong emotional component and face-to-face consultation with medical staff might help to create the right climate of trust, and the empathy that can be demonstrated during a vis-à-vis meeting cannot be achieved through a screen. The use of telemedicine should be considered in those situations where it is not possible to attend an in-person consultation or when couples prefer it.

Use of Azithromycin in Pregnancy: More Doubts than Certainties.

Macrolides such as azithromycin are commonly prescribed antibiotics during pregnancy. The good oral bioavailability and transplacental transfer of azithromycin make this drug suitable for the treatment of sexually transmitted diseases, toxoplasmosis, and malaria. Moreover, azithromycin is useful both in the management of preterm pre-labor rupture of membranes and in the adjunctive prophylaxis for cesarean delivery. The aim of this comprehensive narrative review is to critically analyze and summarize the available literature on the main aspects of azithromycin use in pregnant women, with a special focus on adverse offspring outcomes associated with prenatal exposure to the drug. References for this review were identified through searches of MEDLINE, PubMed, and EMBASE. Fetal and neonatal outcomes following prenatal azithromycin exposure have been investigated in several studies, yielding conflicting results. Increased risks of spontaneous miscarriage, major congenital malformations, cardiovascular malformations, digestive system malformations, preterm birth, and low birth weight have been reported in some studies but not in others. Currently, there is no conclusive evidence to support that azithromycin use by pregnant women causes adverse outcomes in their offspring. Therefore, this agent should only be used during pregnancy when clinically indicated, if the benefits of treatment are expected to outweigh the potential risks.

Native tissue repair (NTR) versus transvaginal mesh interventions for the treatment of anterior vaginal prolapse: Systematic review and meta-analysis.

The aim of the present systematic review and meta-analysis was to compare native tissue repair (NTR) against transvaginal mesh augmentation for the repair of anterior vaginal prolapse. A total of 2289 articles were found but only 27 (24.8 %) were included in the review. Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were followed to guide the process of the systematic review and meta-analysis. The quality of the observational studies was evaluated according to the Scottish Intercollegiate Guidelines Network, whereas the quality of randomized control trials (RCT) was assessed by the Cochrane risk-of-bias scale. The mesh repair intervention was associated with a higher anatomical cure rate in comparison with NTR repair when the follow-up was ≤24 months [pooled risk difference (95 % CI): -0.18 % (-0.22 %; 0.13 %); p-value: <0.0001; I2: 36.0 %]. Studies reporting anatomical failure had similar findings [pooled risk difference (95 % CI): 0.17 % (0.01 %; 0.33 %); p-value: 0.03; I2: 88.6 %]. No differences in the risk of re-operation were observed between NTR repair and mesh augmentation. Pooled risk differences in the incidence of post-surgical and late complications were higher for the mesh repair intervention [-0.05 % (95 % CI: -0.10 %; 0.00 %) p-value: 0.05; I2: 68.3 %] [-0.05 % (95 % CI: -0.14 %; 0.03 %) p-value: 0.25; I2: 82.0 %]. Women who underwent mesh repair reported greater satisfaction than women who underwent NTR [pooled risk difference (95 % CI): -0.07 % (-0.16 %; 0.02 %); p-value: 0.15; I2: 65.3 %]. In conclusion, mesh repair surgery had higher anatomical cure and satisfaction rates, with no differences in re-operation rate, but had higher post-surgical and late complications in comparison with NTR.

Fetal Growth and Neonatal Outcomes in Pregestational Diabetes Mellitus in a Population with a High Prevalence of Diabetes.

The aim of this retrospective study, conducted in an Italian tertiary care hospital, was to evaluate maternal-fetal and neonatal clinical outcomes in a group of patients with pregestational diabetes mellitus (PGDM), such as diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), and maturity onset diabetes of the young (MODY). Overall, 174 pregnant women, nulliparous and multiparous, with a single pregnancy were enrolled. Data on pregnancy, childbirth, and newborns were collected from medical records. The selected patients were divided into two groups: the PGDM group (42 with DM1, 14 with DM2, and 2 with MODY), and the control group (116 patients with a negative pathological history of diabetes mellitus). We reported an incidence of preterm delivery of 55.2% in the PGDM group, including 59.5% of those with DM1 and 42.9% of those with DM2, vs. 6% in the controls. Fetal growth disorders, such as intrauterine growth retardation, small for gestational age, and fetal macrosomia were found in 19% and 3.6% in the case and control groups, respectively. A relationship between DM2 and gestational hypertension was found.

Metformin and vitamin D modulate adipose-derived stem cell differentiation towards the beige phenotype.

Adipose-derived stem cells (ADSCs) represent an ideal stem cell population for regenerative medicine. ADSC adipogenic differentiation is controlled by the activation of a specific transcriptional program, including epigenetic factors and key adipogenic genes. Under certain conditioned media, ADSCs can differentiate into several phenotypes. We previously demonstrated that bioactive molecules could counteract lipid accumulation and regulate adipogenesis, acting on inflammation and vitamin D metabolism. In the present paper, we aimed at evaluating the effect of metformin and vitamin D in targeting ADSC differentiation towards an intermediate phenotype, as beige adipocytes. We exposed ADSCs to different conditioned media and then we evaluated the levels of expression of main markers of adipogenesis, aP2, LPL and ACOT2. We also analysed the gene and protein expression of thermogenic UCP1 protein, and the expression of PARP1 and the beige specific marker TMEM26. Our results showed a novel effect of metformin and vitamin D not only in inhibiting adipogenesis, but also in inducing a specific 'brown-like' phenotype. These findings pave the way for their possible application in the control of de novo lipogenesis useful for the prevention of obesity and its related metabolic disorders.

Thyroid Dysfunction after Gonadotropin-Releasing Hormone Agonist Administration in Women with Thyroid Autoimmunity.

GnRH agonists (GnRHa) are a useful tool for pretreatment before artificial endometrial preparation for frozen-thawed embryo-transfer (FET). Their prolonged administration has been associated with thyroid dysfunction, both hyper and hypothyroidism. The aim of this study is to investigate the impact of GnRHa administration on thyroid function in women undergoing artificial endometrial preparation. Seventy-eight euthyroid women undergoing endometrial preparation with hormone replacement for FET were retrospectively reviewed. They were divided into two groups according to pretreatment with GnRHa (group A, 42 women) or with an oral contraceptive (group B, 36 women). Group A was subsequently divided into two subgroups according to thyroid autoimmunity presence. Thyroid function has been evaluated and compared among groups and subgroups. Our results did not show any statistically significant differences in age, body mass index, and basal thyroid stimulating hormone (TSH). Total estradiol dosage, duration of treatment, and endometrial thickness were comparable among groups. When TSH was measured 14 days after embryo transfer, no significant differences between the two groups were reported. Among women of group A, TSH was significantly higher only in women with thyroid autoimmunity. GnRHa seems to be associated with thyroid dysfunction in women with thyroid autoimmunity undergoing hormone replacement therapy for FET.

Sentinel Lymph Node Biopsy in Surgical Staging for High-Risk Groups of Endometrial Carcinoma Patients.

BACKGROUND: In endometrial carcinoma (EC) patients, sentinel lymph node (SLN) biopsy has shown the potential to reduce post-operative morbidity and long-term complications, and to improve the detection of low-volume metastasis through ultrastaging. However, while it has shown high sensitivity and feasibility in low-risk EC patient groups, its role in high-risk groups is still unclear. AIM: To assess the role of SLN biopsy through the cervical injection of indocyanine green (ICG) in high-risk groups of early-stage EC patients. MATERIALS AND METHODS: Seven electronic databases were searched from their inception to February 2021 for studies that allowed data extraction about detection rate and accuracy of SLN biopsy through the cervical injection of ICG in high-risk groups of early-stage EC patients. We calculated pooled sensitivity, false negative (FN) rate, detection rate of SLN per hemipelvis (DRh), detection rate of SLN per patients (DRp), and bilateral detection rate of SLN (DRb), with 95% confidence interval (CI). RESULTS: Five observational cohort studies (three prospective and two retrospective) assessing 578 high risk EC patients were included. SLN biopsy sensitivity in detecting EC metastasis was 0.90 (95% CI: 0.03-0.95). FN rate was 2.8% (95% CI: 0.6-11.6%). DRh was 88.4% (95% CI: 86-90.5%), DRp was 96.6% (95% CI: 94.7-97.8%), and DRb was 80% (95% CI: 75.4-83.9). CONCLUSION: SLN biopsy through ICG cervical injection may be routinely adopted instead of systematic pelvic and para-aortic lymphadenectomy in surgical staging for high-risk groups of early-stage EC patients, as well as in low-risk groups.