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Gynecologic cancer is a major global health burden, and improvements in screening, surgical techniques, and systemic therapies have significantly prolonged survival. As a result, cardiopulmonary disease has emerged as a leading non-cancer cause of morbidity and mortality among gynecologic cancer survivors. Obesity, which is highly prevalent in this population, substantially increases cardiopulmonary risk by contributing to metabolic syndrome, cardiovascular disease, chronic inflammation, and reduced cardiopulmonary reserve. This narrative review summarizes current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of cardiopulmonary complications in obese patients with gynecologic malignancy. We review the contribution of obesity-related metabolic and endothelial dysfunction, cancer-associated hypercoagulability, and treatment-related toxicities, with particular emphasis on complications arising from surgery, chemotherapy, and radiotherapy. Epidemiologic data demonstrate a markedly increased burden of cardiovascular and pulmonary disease in obese gynecologic cancer patients, including higher rates of myocardial injury, heart failure, venous thromboembolism, and postoperative respiratory complications. Surgical treatment, although central to oncologic management, imposes substantial cardiopulmonary stress, placing obese patients at heightened perioperative risk. Future studies should focus on preoperative risk stratification, optimization of obesity-related comorbidities, and multidisciplinary perioperative management, including enhanced recovery pathways, as well as appropriate use of high-dependency or intensive care monitoring to reduce morbidity and improve both oncologic and long-term non-oncologic outcomes in this population.

Background/Objectives: Cervical cancer (CC) is the fourth most common gynecologic malignancy, disproportionately affecting women in low- and middle-income countries. Despite the effectiveness of HPV vaccination and screening strategies, CC poses a major global health issue, accounting for approximately 94% of annual deaths. Τhis review aims to summarize the current evidence regarding adjuvant treatment indications for surgically treated cervical cancer patients and identify areas where further research is required. Methods: After a literature search, a comprehensive review of the existing guidelines, clinical trials, and cohort studies related to cervical cancer treatment was conducted, focusing on the role of adjuvant therapy in patients classified as at low, intermediate, and high risk for recurrence, who may require no further treatment. Results: Adjuvant therapy is generally unnecessary for low-risk patients, while high-risk patients with lymph node invasion, parametrial involvement, or large tumor size require chemoradiation (CRT). Ιntermediate-risk patients fall into a grey zone, where the necessity of adjuvant therapy is still debatable. Guidelines emphasize the need for individualization in treatment strategies, since, based on the published studies, careful surgery alone and observation can provide similar outcomes to adjuvant therapy. Conclusions: This review emphasizes that achieving monotherapy remains pivotal to optimize outcomes and minimize overtreatment. Definitive adjuvant treatment is indicated for high-risk cases, and intermediate-risk patients may benefit from careful observation following adequate surgical intervention, pointing out the necessity of well-designed clinical trials.

Purpose While cell-free DNA (cfDNA) screening has emerged as a screening modality for common aneuploidies, further research and several publications over the past decade suggested some correlation between the low concentrations of cfDNA and a number of pregnancy-related complications. The primary goal of this systematic review and meta-analysis was to assess the potential value of low-ff levels in the prediction of subsequent PE/PIH, GDM, SGA/FGR, and PTB. The meta-analysis results aim at summarizing the currently available literature data and determining the clinical relevance of this biochemical marker and the potential necessity for additional investigation of its utility in complications other than the detection of common aneuploidies. Methods This systematic review and meta-analysis was designed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. It included all observational studies that reported low -ff levels after the performance of non-invasive prenatal testing (NIPT) as part of the screening for chromosomal abnormalities and their association with adverse pregnancy outcomes, namely the subsequent development of hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and the detection of small for gestational age fetuses or growth-restricted fetuses. The Medline (1966–2041), Scopus (2004–2024), Clinicaltrials.gov (2008–2024), EMBASE (1980–2024), Cochrane Central Register of Controlled Trials CENTRAL (1999–2024) and Google Scholar (2004–2024) databases were used in our primary search along with the reference lists of electronically retrieved full-text papers. The date of our last search was set at February 29, 2024. Results Our search identified 128 potentially relevant studies and,overall, 8 studies were included in the present systematic review that enrolled a total of 72,507 patients. Low ff of cfDNA cfDNA was positively associated with HDP (OR 1.66, 95% CI 1.34, 2.06, I-square test: 56%). Low ff of cfDNA was positively associated with GDM (OR 1.27, 95% CI 1.03, 1.56, I-square test: 76%). Furthermore, low ff levels were positively associated with SGA/FGR (OR 1.63, 95% CI 1.32, 2.03, I-square test: 0%). Low ff levels were positively correlated with the risk for PTB but the association did not manage to reach a statistical significant level (OR 1.22, 95% CI 0.89, 1.67, I-square test: 66%). Conclusion Our study suggests that low ff is associated with increased risk of adverse perinatal outcomes, including PE/PIH, GDM, and SGA/FGR. However, the relationship between ff and PTB remains unclear due to conflicting evidence. It should be emphasized that further research is needed to reveal the underlying mechanisms behind the association of low ff with adverse pregnancy outcomes and explore its potential role in an overall prenatal screening, which could potentially not be limited to detecting aneuploidies.

Background: It is well established in the literature that pregnancy-associated plasma protein-A (PAPP-A) is linked to several adverse pregnancy outcomes, including pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB) in singleton pregnancies. However, data regarding such an association in twin pregnancies are lacking. The primary goal of this systematic review and meta-analysis was to assess the potential value of low PAPP-A levels in the prediction of the subsequent development of hypertensive disorders of pregnancy (HDPs), PTB, and small for gestational age (SGA)/FGR fetuses in twin pregnancies and investigate its association with the development of gestational diabetes, intrauterine death (IUD) of at least one twin, and birth weight discordance (BWD) among the fetuses. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 July 2024. All observational studies reporting low PAPP-A levels after the performance of the first-trimester combined test as part of the screening for chromosomal abnormalities with reported adverse pregnancy outcomes were included. Results: The current systematic review encompassed a total of 11 studies (among which 6 were included in the current meta-analysis) that enrolled a total of 3741 patients. Low PAPP-A levels were not associated with HDPs (OR 1.25, 95% CI 0.78, 2.02, I-square test: 13%). Low PAPP-A levels were positively associated with both the development of preterm birth prior to 32 (OR 2.85, 95% CI 1.70, 4.77, I-square test: 0%) and 34 weeks of gestational age (OR 2.09, 95% CI 1.34, 3.28, I-square test: 0%). Furthermore, low PAPP-A levels were positively associated with SGA/FGR (OR 1.58, 95% CI 1.04, 2.41, I-square test: 0%). Prediction intervals indicated that the sample size that was used did not suffice to support these findings in future studies. Conclusions: Our study indicated that low PAPP-A levels are correlated with an increased incidence of adverse perinatal outcomes in twin pregnancies. Identifying women at elevated risk for such adversities in twin pregnancies may facilitate appropriate management and potential interventions, but additional studies are required to identify the underlying mechanism linking PAPP-A with those obstetrical complications.

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021–2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415–6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887–13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400–9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51–15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02–16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05–15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

BackgroundVascular clamping of the uterine vessels and the ovarian and broad ligaments during vaginal hysterectomies is more difficult than in traditional abdominal hysterectomies. We aimed to assess the efficacy of electrosurgical bipolar vessel sealing systems (EBVS) as an adequate alternative to traditional suturing that could facilitate the accomplishment of securing the vascular pedicles.MethodsWe searched MEDLINE (1966–2013), Scopus (2004–2013), POPLINE (1973–2013), Cochrane Central (1999–2013) and Google Scholar (2004–2013) search engines, along with reference lists from all included studies.ResultsEight randomized trials were selected, including 772 patients. We found that operative duration did not differ significantly among women treated with EBVS and those treated with traditional suture ligation (MD −16.86, 95 % CI −34.77, 1.05). Intraoperative blood loss on the other hand was significantly lower in the EBVS-treated group (MD −49.47, 95 % CI −67.60, −31.35). There were no significant differences in intraoperative complication rates (OR 0.96, 95 % CI 0.46, 2.01), major postoperative complication rates (OR 0.61, 95 % CI 0.29, 1.32) or minor complications (OR 1.63, 95 % CI 0.67, 3.92).ConclusionOur meta-analysis showed that EBVS seem to produce less intraoperative blood loss during vascular clamping, without significantly lowering intraoperative time or complication rate. However, the heterogeneity of included studies preclude firm conclusions. Future studies examine consistently their safety, and cost-effectiveness, and whether the application of such units will enhance the rates of vaginal hysterectomies.

Fetal alcohol spectrum disorder (FASD) is one of the main causes of mental retardation worldwide. Nearly 1% of children in North America are affected from antenatal exposure to ethanol. Its economic burden in industrialized countries is increasing. It is estimated that, in the United States, 4.0 billion dollars are annually expended in the treatment and rehabilitation of these patients. As a pathologic entity, they present with a broad symptomatology. Fetal alcohol syndrome (FAS) is the most readily recognized clinical manifestation of these disorders. Various factors seem to contribute in the pathogenesis of FASD-related cognitive disorders. During the last 20 years, several potential pretranslational and posttranslational factors have been extensively studied in various experimental animal models. Research has specifically focused on several neurotransmitters, insulin resistance, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, abnormal glycosylation of several proteins, oxidative stress, nutritional antioxidants, and various epigenetic factors. The purpose of the present review is to summarize the clinical manifestations of this disorder during childhood and adolescence and to summarize the possible pathophysiologic and epigenetic pathways that have been implicated in the pathophysiology of FASD.

Background: Human Papilloma Virus has been considered as the main cause for cervical cancer. In this study we investigated epigenetic changes and especially methylation of specific sites of HPV genome. The main goal was to correlate methylation status with histological grade as well as to determine its accuracy in predicting the disease severity by establishing optimum methylation cutoffs. Methods: In total, sections from 145 cases genotyped as HPV16 were obtained from formalin- fixed, paraffin-embedded tissue of cervical biopsies, conization or hysterectomy specimens. Highly accurate pyrosequencing of bisulfite converted DNA, was used to quantify the methylation percentages of UTR promoter, enhancer and 5' UTR, E6 CpGs 494, 502, 506 and E7 CpGs 765, 780, 790. The samples were separated in different groupings based on the histological outcome. Statistical analysis was performed by SAS 9.4 for Windows and methylation cutoffs were identified by MATLAB programming language. Results: The most important methylation sites were at the enhancer and especially UTR 7535 and 7553 sites. Specifically for CIN3+ (i.e. HSIL or SCC) discrimination, a balanced sensitivity vs. specificity (68.1%, 66.2% respectively) with positive predictive value (PPV) and negative predictive value (NPV) (66.2%, 68.2% respectively) was achieved for UTR 7535 methylation of 6.1% cutoff with overall accuracy 67.1%, while for UTR 7553 a sensitivity 60.9%, specificity 69.0%, PPV=65.6%, NPV=64.5% and overall accuracy=65.0% at threshold 10.1% was observed. Conclusion: Viral HPV16 genome was found methylated in NF-1 binding sites of UTR in cases with high grade disease. Methylation percentages of E6 and E7 CpG sites were elevated at the cancer group.