Triple Negative Breast Cancer: Molecular Subtype-Specific Immune Landscapes with Therapeutic Implications.

Triple Negative Breast Cancer (TNBC) is characterized by distinct molecular subtypes with unique biological and clinical features. This systematic review aimed to identify articles examining the differences in the tumor immune microenvironment (TIME) across different TNBC molecular subtypes. Six studies meeting inclusion criteria were analyzed, utilizing gene expression profiling and bioinformatic analyses to classify TNBC samples into molecular subtypes, as well as immunohistochemistry and cell deconvolution methods to characterize the TIME. Results revealed significant heterogeneity in immune cell composition among TNBC subtypes, with the immunomodulatory (IM) subtype demonstrating robust immune infiltration, composed mainly of adaptive immune cells along with an increased density of CTLA-4+ and PD-1+ TILs, high PD-L1 tumor cell expression, and upregulation of FOXP3+ Tregs. A more immunosuppressive TIME with a predominance of innate immune cells and lower levels of tumor-infiltrating lymphocytes (TILs) was observed in luminal androgen receptor (LAR) tumors. In mesenchymal stem-like (MSL) tumors, the TIME was mainly composed of innate immune cells, with a high number of M2 tumor-associated macrophages (TAMs), while the BL and M tumors displayed poor adaptive and innate immune responses, indicating an "immune-cold" phenotype. Differential activation of signaling pathways, genomic diversity, and metabolic reprogramming were identified as contributors to TIME heterogeneity. Understanding this interplay is crucial for tailoring therapeutic strategies, especially regarding immunotherapy.

Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study.

Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers.

Prophylactic Antibiotics before Gynecologic Surgery: A Comprehensive Review of Guidelines.

Surgical site infections (SSIs) refer to infections in the incision, organ, or postoperative space. As common healthcare-associated infections, SSIs correlate with prolonged hospital stay, additional procedures, ICU stay, and higher mortality rates. Around 8-10% of gynecologic surgery patients may experience infectious complications, influenced by microbial contamination, surgical nature, and patient factors. The goal of this narrative review is to compare and merge recommendations from globally published guidelines concerning the utilization of antibiotics in the perioperative phase. A comparative descriptive/narrative review of the guidelines issued by the American College of Obstetrics and Gynecology (ACOG), Society of Obstetricians and Gynecologists of Canada (SOGC), Royal College of Obstetricians and Gynecologists (RCOG), National Institute for Health and Care Excellence (NICE), Royal Australian and New Zealand College of Obstetricians and Gynecologists (RANZCOG), European Society of Gynecologic Oncology (ESGO), Société Française d' Anésthesie et de Réanimation (SFAR), Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), and Hellenic Society of Obstetrics and Gynecology (HSOG) was conducted. For hysterectomy, first/second-generation cephalosporins are suggested, with metronidazole as an option. Laparoscopy without entering the bowel or vagina typically does not require prophylaxis. Uterine evacuation and hysteroscopy may involve doxycycline or azithromycin based on risk factors, whereas, for vulvectomy, cefazolin is recommended. Urogynecology procedures may include cefazolin with metronidazole. In cases of penicillin allergy, cephalosporins are suggested, and, for obese patients, adjusted doses are advised. Additional doses may be needed for prolonged procedures or excessive blood loss. Timing recommendations are 15-60 min before incision, adjusting for specific antibiotics. Clear indications exist for certain surgeries like hysterectomy, termination of pregnancy, and urogynecologic procedures. Conversely, procedures such as intrauterine device insertion, hysteroscopy, and laparoscopy typically do not necessitate antibiotic prophylaxis. For several other procedures, the evidence is inconclusive, while considering dose, timing, and indications can mitigate infectious complications and provide benefits for the healthcare system.

Clinical significance and main parameters promoting the breast­feeding strategy (Review).

Breastfeeding provides numerous nutritional and immunological benefits, promotes neurological and cognitive development, and protects against chronic and infectious diseases, rendering it beneficial to the survival and well-being of infants. According to international recommendations, infants should be exclusively breastfed for the first 6 months. However, despite global health recommendations and funding initiatives, exclusive breastfeeding rates remain low worldwide. A number of studies attribute the low rates to factors that can be grouped into demographic, psychosocial, economic and midwifery factors, and outline the profile of each mother who opts to exclusively breastfeed her infant. In addition, the number of previous pregnancies, induced labor, the use of epidurals at birth or the possibility of the newborn being delivered prematurely, and the need for admission to an intensive care unit are the factors that reduce the likelihood of exclusive breastfeeding. Further research is required to understand the factors influencing the initiation and maintenance of exclusive breastfeeding, as international interventions have been ineffective. The aim of the present review was to provide an up-to-date summary of these various factors in an aim to assist health care professionals and policy makers in developing effective interventions with which to promote and support exclusive breastfeeding.

Human papillomaviruses and breast cancer: A systematic review and meta­analysis.

Breast cancer (BC) is the leading malignancy worldwide. The association between human papillomavirus (HPV) and BC is debatable. The present systematic review and meta-analysis aimed to assess the prevalence of HPV DNA in malignant breast tumors. An extensive search of the PubMed and SCOPUS databases was carried out for case-control studies published between January 1, 2003 and January 7, 2023, which compared HPV DNA detection in breast tissue specimens of female patients with BC and women with absent or benign breast disorders. Once the initial title/abstract screening was completed by two independent investigators, the full texts of the included studies from that stage were reviewed by the aforementioned investigators to determine if they should be included in the present study. Data extraction was independently conducted by two investigators. A third investigator was consulted to resolve disagreements through free discussion. MedCalc was used for quantitative synthesis. The significance of association was estimated by pooled odds ratios (ORs) with 95% confidence intervals (CIs) calculated using the random-effects model. A total of 23 primary studies, including 3,243 subjects (2,027 patients and 1,216 controls), were eligible for quantitative analysis. HPV prevalence in patients with BC and controls was 21.95 and 8.96%, respectively. The prevalence of HPV differed significantly between the two groups (OR 3.83; 95% CI 2.03-7.25; P<0.01). Heterogeneity among studies was quantified using the I2 index which was 69.57% (95% CI 51.89-80.75). The risk of bias was assessed using an appropriate tool contributed by the CLARITY Group at McMaster University. Seven studies had a low risk of bias, 15 studies had a moderate risk of bias and only one study had a serious risk of bias. These results reinforce the hypothesis that HPV is involved in BC development and progression, indicating a possible role of HPV vaccination in BC prevention.

Sentinel lymph node biopsy for breast cancer during pregnancy: A comprehensive update.

BACKGROUND: Pregnant patients diagnosed with breast cancer (PrBC) may receive substantially different treatments compared to general population, considering that certain treatment options cannot be applied during pregnancy due to their potential harmful effects to the foetus. Regarding the use of sentinel lymph node biopsy (SLNB) in pregnant patients, potential concerns include foetal harm from radiation exposure, possible teratogenic effects of blue dyes and maternal anaphylaxis to isosulfan. OBJECTIVE: The main objective of the present systematic review is to summarize and present current knowledge and up-to-date evidence about the safety and efficacy of SLNB in PABC. METHODS: MEDLINE, Google Scholar and UpToDate databases were searched up to 22 January 2023. Articles studying the safety and effectiveness of SLNB in patients for PrBC were eligible for inclusion in the present review. RESULTS: In total, 63 articles that met the inclusion criteria were included in this study. Forty-seven articles were strongly in favour of performing SLNB in PABC, 4 articles were partially in favour, 10 articles were strongly against and 2 articles were partially against performing SLNB in PABC. Sub-categorization based on type of study showed that the majority of studies in favour were of higher level of evidence than those against. Furthermore, there were overall 12 studies reporting on outcomes. There were overall 382 women with PrBC that underwent SLNB. Full data were reported for 237 cases. Overall live birth rate was 95.8%, while overall neonatal complication rate was 3.4%. No case of maternal side effects or anaphylactic reaction, maternal death, stillbirth and neonatal death was reported (0%). CONCLUSIONS: Sentinel lymph node biopsy seems to be safe and effective technique for breast cancer during pregnancy.

Uterine Arteries Resistance in Pregnant Women with Gestational Diabetes Mellitus, Diabetes Mellitus Type 1, Diabetes Mellitus Type 2, and Uncomplicated Pregnancies.

BACKGROUND: The examination of the uterine arteries using Doppler in the first trimester of pregnancy serves as a valuable tool for evaluating the uteroplacental circulation. Diabetes mellitus is associated with altered placental implantation and pregnancy-related pathologies, such as preeclampsia. The aim of this study was to compare the uterine arteries' pulsatility indices (UtA PI) in women with diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), gestational diabetes mellitus (GDM), and uncomplicated pregnancies. METHODS: This was a retrospective case-control trial including pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, presenting for first-trimester ultrasound screening in two tertiary university hospitals between 2013 and 2023. The first-trimester UtA pulsatility index (PI), expressed in multiples of medians (MoMs), was compared between the four groups. RESULTS: Out of 15,638 pregnant women, 58 women with DM1, 67 women with DM2, 65 women with GDM, and 65 women with uncomplicated pregnancies were included. The mean UtA PI were 1.00 ± 0.26 MoMs, 1.04 ± 0.32 MoMs, 1.02 ± 0.31 MoMs, and 1.08 ± 0.33 MoMs in pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, respectively (p > 0.05). CONCLUSIONS: Potential alterations in the implantation of the placenta in pregnant women with diabetes were not displayed in the first-trimester pulsatility indices of the uterine arteries, as there were no changes between the groups.

Mixed High-Risk Endometrial Carcinoma Initially Presented With Atypical Squamous Cells of Undetermined Significance (ASC-US) Cytology: Lessons to Be Learned.

Endometrial carcinoma represents the most common gynecologic malignancy, affecting mainly postmenopausal women. Early detection and proper management may allow not only a successful treatment but also an acceptable quality of life. Although its usual clinical manifestations, such as vaginal bleeding or a mass stuck out of the cervix, often arouse medical concern, in some cases, there is a dilemma regarding the differential diagnosis of endocervical cancer. Additionally, tumors arising from and confined to the uterine isthmus may often pose a greater diagnostic challenge. Defining the primary origin of the carcinoma is of paramount importance as the treatment plan may be widely different in these two scenarios. Magnetic Resonance Imaging (MRI), markers, and biopsy with immunohistochemistry could facilitate the diagnostic process, but the final diagnosis may even be made from the final surgical specimen in such demanding cases. We present the case of a mixed-type, stage IIIC2, endometrial carcinoma arising from the lower uterine segment initially suspected from atypical squamous cells of undetermined significance (ASC-US) cytology.

The Impact of a Single Supervised Exercise Session in the Third Trimester of Pregnancy on the Physical Activity Levels of Pregnant Women-A Pilot Study.

BACKGROUND: Despite the numerous beneficial effects of physical exercise during pregnancy, the levels of physical activity remain low. The aim of the study is to investigate the impact of a single supervised physical exercise session on the overall physical activity levels of pregnant women. METHODS: During the third trimester, pregnant women attending our outpatient clinic were requested to assess their physical activity levels using the International Physical Activity Questionnaire (IPAQ). Additionally, they were invited to participate in a supervised 30 min mild-moderate-intensity aerobic exercise session (stationary bike ergometer) under the guidance of medical personnel. Subsequently, physical activity levels were reevaluated at the time of delivery. RESULTS: Prior to the intervention, 3 out of 50 (6%) women engaged in mild-moderate physical activity for 150 min per week, while 20 out of 50 (40%) women participated in mild-moderate activity for 15-30 min, twice a week. Following the intervention, these percentages increased to 10 out of 50 (20%) and 31 out of 50 (62%), respectively (p < 0.05). CONCLUSIONS: This pilot study suggests that a single exercise session supervised by medical personnel may significantly improve the low physical activity levels observed in pregnant women.

Pregnancy outcomes in the different phenotypes of gestational diabetes mellitus based on the oral glucose tolerance test. A systematic review and meta-analysis.

AIMS: To assess the prevalence variation in pregnancy outcomes of the different phenotypes of gestational diabetes mellitus (GDM). MATERIALS: Cohort, cross sectional and case control studies grouping together pregnant women with GDM, based on the results of oral glucose tolerance test(OGTT) and reporting pregnancy outcomes in each group, were included. The primary outcomes were (i)large for gestational age and ii)hypertensive disorders of pregnancy (HDP). The secondary outcomes included (i)insulin treatment, ii)admission to neonatal intensive care unit, iii)preterm birth, iv)small for gestational age and v)caesarean section. The pooled proportions of the outcomes of interest were calculated for each phenotype. RESULTS: 8 studies (n = 20.928 women with GDM) were included. The pooled prevalence of LGA, HDP and insulin treatment were 20 %, 8 % and 24 % respectively in women with abnormal fasting plasma glucose,10 %, 6 % and 9 % respectively in women with abnormal post-load plasma glucose and 14 %,14 % and 30 % in women with abnormal combined plasma glucose. CONCLUSIONS: Pregnant women with abnormal fasting plasma glucose, present with the highest prevalence of LGA, while those with abnormal combined plasma glucose, present with the highest prevalence of HDP. Pregnant women with abnormal post-load plasma glucose present with the lowest need for insulin treatment.

HIPEC for gynaecological malignancies: A last update (Review).

Advanced-stage gynaecological cancer represents a clinical entity with challenging surgical treatment in an effort to optimize prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS) has been reported as a method potentially eligible to improve prognosis. However, no definitive conclusions have yet been made on which types of cancer and which context HIPEC may actually have a beneficial impact. The present review discusses the efficacy and safety of HIPEC as a treatment option for patients with primary/recurrent ovarian, endometrial and cervix cancer, as well as peritoneal sarcomatosis. A literature search was conducted using MeSH terms for each topic in the PubMed database and supplemented with a manual search to retrieve additional articles eligible for inclusion/fulfilling the inclusion criteria. The implementation of HIPEC appears to be beneficial in terms of survival in patients with epithelial ovarian carcinoma (EOC) following neoadjuvant chemotherapy, as well as in patients with recurrent EOC. Statistical superiority is not justified by current studies regarding other gynaecological malignancies with peritoneal dissemination. Furthermore, as regards safety, HIPEC following CRS does not appear to significantly increase the mortality and morbidity rates compared to the use of CRS alone. The rationale for using HIPEC and CRS in the treatment of ovarian cancer, particularly in the neoadjuvant setting, as well as for recurrences, is adequately evidenced, with acceptable safety and post-operative complication rate profiles. Its current place in the multimodal strategy for patients with peritoneal metastases remains uncertain, however. Randomized clinical trials are warranted to further examine the use of HIPEC and establish the optimal regimen and temperature settings. The role of optimal cytoreduction and no residual disease, as well as the proper patient selection remain basic parameters for maximizing survival parameters.

Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real-time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients.

BACKGROUND: Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples. METHODS: Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT-PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases. RESULTS: A total of three different HPV types were identified within the patient sample. HPV-39 was found only in the control group, in 1.8% of patients, while HPV-59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV-16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV-16 was exclusively in IDC, HPV-39 was present in one cyst diagnosed sample and HPV-59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis. CONCLUSION: More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.

Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal Adverse Outcomes.

Breast cancer is a common type of cancer diagnosed during pregnancy, with increasing incidence over the last years, as more women choose to delay childbearing. Compared to breast cancer in general population, pregnancy-associated breast cancer (PABC) is significantly different in its terms of epidemiology, diagnostic and therapeutic management, while it exhibits particularly aggressive behavior, deriving from its unique molecular and biological profile. Although not fully elucidated, the pathophysiological basis of PABC can be traced back to a combination of hormonal and immune changes during pregnancy, breast involution and altered gene expression. There is considerable controversy in the existing literature about the influence of PABC on pregnancy outcomes, regarding both short- and long-term effects on maternal and fetal/neonatal health. The majority of PABC patients have advanced-stage disease at initial diagnosis and face a significantly poorer prognosis, with decreased survival rates. The most commonly reported adverse obstetrical-fetal events are preterm delivery and prematurity-associated neonatal morbidity, while other neonatal treatment-associated complications might also occur, even when safe therapeutic options are applied during pregnancy. The objective of the present comprehensive review was to summarize current knowledge and up-to-date evidence about the pathophysiological, molecular and biological basis of PABC, as well as its association with adverse maternal, obstetrical, fetal and neonatal outcomes.

Therapeutic Management and Prognostic Factors for Ovarian Malignant Tumours in Adolescents: A Comprehensive Review of Current Guidelines.

Background: Ovarian malignant tumours are rarely diagnosed in adolescents but may have a significant impact on their survival, future fertility and quality of life. The management of such cases is rather complex and requires expertise and careful planning according to scarce existing evidence and recommendations. Objective: The aim of this study was to review and compare recommendations from published guidelines regarding the diagnosis, prognosis and treatment of malignant ovarian tumours in adolescents. Evidence acquisition: A comparative descriptive/narrative review of guidelines issued by L'Observatoire des Tumeurs Malignes Rares Gynécologiques, the British Society for Paediatric & Adolescent Gynaecology, the European Society for Medical Oncology, the European Society of Gynecological Oncology-European Society for Paediatric Oncology and the European Cooperative Study Group for Pediatric Rare Tumors was conducted. Results: All guidelines recommend a thorough diagnostic work-up, consisting of both imaging tests and serum tumour marker measurement, as well as the use of immunohistochemical methods to confirm the diagnosis and complete surgical staging prior to constructing the treatment plan. There is a lack of recommendations regarding the assessment of prognostic factors, with only one guideline providing detailed information. Treatment strategies, as suggested by the majority of guidelines and with only a few discrepancies between them, should include both surgery and adjuvant therapies, mainly chemotherapy, with great emphasis on fertility preservation when it is considered oncologically safe and on the significance of regular and long-term follow-up. Conclusions: There is a significant degree of agreement among recommendations of existing guidelines. The reported differences, although limited, highlight the need for the adoption of an international consensus in order to further improve the management of adolescent ovarian cancer.

Sarcoma Botryoides: Optimal Therapeutic Management and Prognosis of an Unfavorable Malignant Neoplasm of Female Children.

Embryonal rhabdomyosarcoma (ERMS) is a rare malignancy and occurs primarily in the first two decades of life. Botryoid rhabdomyosarcoma is an aggressive subtype of ERMS that often manifests in the genital tract of female infants and children. Due to its rarity, the optimal treatment approach has been a matter of debate. We conducted a search in the PubMed database and supplemented it with a manual search to retrieve additional papers eligible for inclusion. We retrieved 13 case reports and case series, from which we summarized that the current trend is to approach each patient with a personalized treatment plan. This consists of a combination of local debulking surgery and adjuvant or neoadjuvant chemotherapy (NACT). Effort is made in every approach to avoid radiation for the sake of preserving fertility. Radical surgeries and radiation still have a role to play in extensive disease and in cases of relapse. Despite the rarity and aggressiveness of this tumor, disease-free survival and overall prognosis is excellent, especially when it is diagnosed early, compared with other subtypes of rhabdomyosarcoma (RMS). We conclude that the practice of a multidisciplinary approach is appropriate, with favorable outcomes; however, larger-scale studies need to be organized to have a definite consensus on optimal management.

Diagnostic comparison of electrical impedance spectroscopy with colposcopy and HPV mRNA-testing in the prediction of CIN2+ women in Greece.

AIM: To compare the diagnostic parameters of electrical impedance spectroscopy (EIS) via ZedScan, a device that measures spectra to differentiate between normal and abnormal cervical tissues, when used as an adjunct to colposcopies in the diagnosis of HSILs/CIN2+ in Greek women with abnormal referral cytology toward colposcopy alone and HPV mRNA-testing. METHODS: This study analyzed 86 women, patients of the Colposcopy and Cervical Pathology Clinic of 2nd Obstetrics and Gynecology Department, Aristotle University of Thessaloniki at Hippokration General Hospital, between January 2022 and September 2022. During the visits, women were subjected to cytology, colposcopy alone and then with EIS/ZedScan and histological sampling. RESULTS: Common use of colposcopies and EIS/ZedScan allowed detecting an additional 14 cases of CIN2+ (16.2%) that colposcopy alone failed to report. EIS enhanced the sensitivity of colposcopy from 80.65% to 100% equal with that of HPV-mRNA test while retaining a high specificity (94.74%) which is much higher than specificity of HPV mRNA-testing (65.45%). EIS-assisted colposcopy had the highest value combination of positive and negative predictive values (96.15% and 100%) compared to colposcopy alone (100% and 75%) and HPV mRNA-testing (72.46% and 100%). CONCLUSIONS: Colposcopies performed with EIS/ZedScan demonstrated effectiveness in the diagnosing of CIN2+ leading to a significant increase in the number of CIN2+ that would have been missed if only colposcopy was applied especially in women with LSIL referral cytology. EIS/ZedScan seems to possess the ideal diagnostic threshold for sensitivity, specificity, and predictive values for CIN2+ compared to colposcopy alone and HPV mRNA-testing.

Prevalence of preeclampsia and uterine arteries resistance in the different phenotypes of gestational diabetes mellitus.

AIMS: This study aims to investigate the different phenotypes of Gestational Diabetes Mellitus (GDM), in correlation to preeclampsia and uterine arteries resistance. MATERIALS: This is a prospective cohort study including women with and without GDM per the IADPSG criteria. Three phenotypes of GDM emerged, women with only abnormal fasting (AF) glucose levels, women with only abnormal post-load (AP) glucose levels at 60' and/or 120' and women with abnormal combined (AC) fasting and post-load glucose values. All women underwent uterine arteries doppler examination in the three trimesters and assessed for preeclampsia development. Linear regression was used to express the trajectories of uterine arteries resistance throughout the pregnancy. RESULTS: 6928 pregnant women were included, 5274 without GDM and 1654 with GDM. 546, 781 and 327 of GDM pregnancies presented with AF, AP and AC phenotypes respectively. Prevalence of preeclampsia was 17.9%, 26.8% and 30% in the AF, AP and AC phenotypes respectively (p < 0.001). In women who developed preeclampsia, AC phenotype presented with statistically different trajectory of Uterine Arteries Pulsatility Index Percentiles b = 0.129 than women without GDM and women with AP GDM phenotype b = -0.015 and b = -0.016 respectively. CONCLUSIONS: The combined abnormal phenotype presents with the highest rate of preeclampsia and the most distinct pattern of uterine arteries resistance.

Decreased flow-mediated dilation in gestational diabetes in pregnancy and post-partum. A systematic review and meta-analysis.

AIMS: Gestational diabetes mellitus (GDM) is a common medical complication during pregnancy. Endothelial dysfunction is considered an early step in the progression of atherosclerosis that may contribute to subclinical target organ damage. This meta-analysis aimed to systemically review the existing data regarding endothelial dysfunction between women with and without GDM during pregnancy and post-partum using flow-mediated dilation (FMD). MATERIALS AND METHODS: Eligible studies (cohort and observational) published until October 2021 were identified in the MEDLINE, Scopus, Cochrane Library database and grey literature sources were searched. RESULTS: The search yielded 2272 studies, of which 17 were fully reviewed and 12 studies (N = 740 pregnant women) were finally included. Pregnant women with GDM exhibited a significantly lower FMD compared to pregnant women without GDM (pooled mean difference -3.12; 95% CI -5.36 to -0.88). Moreover, in the immediate (1-6 months) post-partum period, women with previous GDM showed lower FMD compared to healthy women without GDM history (pooled mean difference -7.52; 95% CI -9.44 to -5.59), whereas FMD did not differ in the late post-partum period (more than 4 years). CONCLUSIONS: Flow-mediated dilation is decreased in women with GDM during pregnancy and in the immediate post-partum period, compared to women without GDM, indicating that the endothelial dysfunction noted during the pregnancy in those women persists in the immediate post-partum period too. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42021283113 (www. CLINICALTRIALS: gov).

Sentinel Lymph Node Staging in Early-Stage Cervical Cancer: A Comprehensive Review.

Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for the final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false-negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.

The expression and possible role of corticotropin-releasing hormone family peptides and their corresponding receptors in gynaecological malignancies and premalignant conditions: a systematic review.

The aim of this systematic review is to investigate the impact of corticotropin-releasing hormone (CRH) family peptides and their corresponding receptors on human physiology and disease onset, with a specific focus on gynaecological malignancies such as breast, endometrial, ovarian, vulvar, and cervical cancer. A comprehensive systematic review of 3 medical databases was conducted by 2 independent reviewers. We reviewed studies that explored the expression and role of CRH peptides in various aspects of cancer biology, in the context of breast, endometrial, ovarian, vulvar, and cervical cancer. Our findings reveal that CRH family peptides and their receptors, CRHR1 and CRHR2, are expressed in diverse gynaecological tissues, including cancer cells. Notably, we observed differential expression patterns among different gynaecological cancer types and stages, indicating potential associations with tumour aggressiveness and patient prognosis. Furthermore, CRH peptides were found to exert significant influences on critical cellular processes, such as cell proliferation, migration, invasion, and immune response, in gynaecological cancers. These findings highlight the multifaceted roles of CRH family peptides in gynaecological malignancies and emphasize the need for further research in this field. Therefore, understanding the mechanisms underlying the involvement of CRH family peptides in tumourigenesis may open new avenues for targeted therapeutic strategies in gynaecological malignancies.