Aberrant right subclavian artery (ARSA) is the most frequent aortic-arch branching variant on prenatal sonography, and its clinical relevance is governed by the phenotypic context in which it is detected. Genotype-phenotype interpretation remains complicated by uneven genetic testing uptake and the additional anomaly burden carried in non-isolated cases. This retrospective single-center cohort comprised 350 singleton pregnancies in which ARSA was diagnosed prenatally at a tertiary perinatology center between January 2020 and April 2025. Cases were classified as isolated ARSA (n = 200), ARSA with soft markers (n = 80), or non-isolated ARSA (n = 70). The primary outcome was chromosomal abnormalities, reported with explicit denominator separation: whole-cohort prevalence and diagnostic yield among invasively tested fetuses. The 22q11.2 deletion case definition required dual confirmation by FISH and chromosomal microarray analysis (CMA). Marker- and anomaly-specific yields were examined to identify findings most strongly linked to chromosomal and adverse pregnancy outcomes. Genetic evaluation acceptance varied by phenotype (75.0% isolated, 92.5% soft markers, 92.9% non-isolated; p < 0.001). Whole-cohort chromosomal-abnormality prevalence was 4.5%, 17.5%, and 32.9%; diagnostic yield among invasively tested fetuses was 6.0%, 18.9%, and 35.4%. Trisomy 21 was the most frequent abnormality across phenotypes. Five 22q11.2 deletions (1/1/3 across phenotypes) fulfilled the dual-confirmation criteria; all three non-isolated 22q11.2 cases harbored a conotruncal cardiac anomaly. Marker co-occurrence (≥2 markers, 43.8% of soft-markers) and concurrent major anomalies (≥2, 44.3% of non-isolated) drove yield. Live-birth rates were 97.5%, 87.5%, and 71.4% (p < 0.001). On multivariable logistic regression, ARSA with soft markers (adjusted OR 4.52; 95% CI 1.86-10.96) and non-isolated ARSA (adjusted OR 10.51; 95% CI 4.52-24.44) remained independent predictors of chromosomal abnormality (optimism-corrected AUC 0.708). A compound phenotype (major anomaly + ≥2 soft markers) was present in 25.7% of non-isolated fetuses. Phenotype-based classification of prenatal ARSA reveals a significant risk gradient for chromosomal abnormality and adverse pregnancy outcome, with co-occurring markers and conotruncal anomalies emerging as the strongest individual signals. The findings support risk-concordant counseling: conservative invasive testing in confirmed isolated ARSA, intensified evaluation when soft markers co-occur, and a compound-phenotype-aware, anatomy-directed approach, including CMA and 22q11.2-targeted testing for conotruncal lesions, in the non-isolated subgroup.
To evaluate the association of anterior cerebral artery (ACA) and posterior cerebral artery (PCA) Doppler parameters with adverse perinatal outcomes in pregnancies complicated by late-onset fetal growth restriction (FGR), and assess their potential complementary prognostic role alongside conventional middle cerebral artery (MCA) Doppler assessment. This prospective observational study included 130 pregnancies diagnosed with late-onset FGR between 32 and 37 weeks of gestation at a tertiary perinatology center. Doppler evaluation included umbilical artery (UA), uterine artery, MCA, ACA, and PCA. The cerebroplacental ratio (CPR) was calculated as MCA PI/UA PI. The primary outcome was composite adverse perinatal outcome defined as perinatal death, 5-min Apgar score <7, umbilical artery pH < 7.20, neonatal intensive care unit (NICU) admission, or need for mechanical ventilation. Predictive performance of Doppler parameters was assessed using receiver operating characteristic (ROC) analysis and multivariable logistic regression. Composite adverse perinatal outcomes occurred in 45 pregnancies (34.6%). Pregnancies with adverse outcomes had significantly higher UA PI and lower cerebral Doppler indices, including MCA PI (p = 0.004), ACA PI (p = 0.021), PCA PI (p = 0.036), and CPR (p = 0.002). CPR showed the highest discriminative performance (AUC = 0.85; 95%CI: 0.77-0.92), followed by MCA PI (AUC = 0.80), ACA PI (AUC = 0.74), and PCA PI (AUC = 0.70). In multivariable analysis, MCA PI, ACA PI, PCA PI, and estimated fetal weight percentile were independent predictors of adverse perinatal outcome. In late-onset FGR, Doppler abnormalities in the anterior and posterior cerebral arteries were associated with adverse perinatal outcomes. Assessment of ACA and PCA Doppler parameters may provide complementary prognostic information regarding fetal cerebral hemodynamic adaptation alongside conventional MCA and CPR evaluation.
This study aimed to develop international expert consensus statements on chronic endometritis (CE) through a comprehensive literature review of existing evidence and a modified Delphi approach. Ten panelists of the Japan Society of Reproductive Medicine Female Reproductive Tract Special Interest Group on CE performed a comprehensive review of the literature and derived statements with related comments on six specific domains of interest on CE. A two-round modified e-Delphi questionnaire was conducted among 31 international experts to evaluate the statements. Twenty-three out of 24 statements, including 43 detailed items, on epidemiology (associated diseases and risk factors), symptomatology (asymptomatic or oligosymptomatic nature with subtle and nondescript gynecologic manifestations), etiology and pathogenesis (inflammation, infection, and clinical course), microbiology (associated pathogens), diagnosis (histopathology, immunohistochemistry, hysteroscopy, and microbiome analysis), and treatment (antibiotics, surgery, and multidrug resistance) finally reached a consensus. Notably, for the histopathologic diagnosis of CE, a threshold of ≥ 5 endometrial stromal plasma cells/10 high-power fields received an agreement rate of 81%. This comprehensive literature review and Delphi study provide a real-world clinical perspective on CE from diverse international experts. These consensus statements have the potential to lay a foundation for diagnostic criteria and/or clinical guidelines on CE.
Our goal was to summarize the previous management of pregnant women with LQTS, as well as to present the current guidelines in this area. We conducted a systematic search in multiple databases, including PubMed, Scopus, and Medline/Embase between 1984 and 2022. Original articles were eligible if they included pregnant patients suffering from congenital long QT syndrome with the three most common types 1-3. The subject-related articles were processed according to Preferred Reporting Items in Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two authors independently screened studies, extracted data, and assessed methodological quality. A total of 15 publications were included in the final report. In the literature, 18 cases of long QT syndrome with the most common types in pregnant women were included, for a final total of 20 cases. Despite the advances in medicine there is a lack of studies that can determine unequivocally, the only right way to manage pregnant women suffering from long QT syndrome. The question remains - does cesarean section objectively reduce the risk of cardiovascular complications in such cases? There is a strong need for further research in this scientific field, especially to create opportunities to reduce the performance of unjustified cesarean sections and thus improve mother and neonatal outcomes. It is believed that the actual incidence of LQTS is significantly higher than current statistics report, therefore, it is so vital to standardize the management of this group of patients.
Amniotic fluid sludge (AFS) is a sonographic finding associated with intra-amniotic infection and spontaneous preterm birth. The microbial composition of AFS remains poorly characterized. This systematic review and meta-analysis aimed to consolidate existing data on microbial prevalence in AFS and identify consistent microbial patterns. A systematic search of MEDLINE (PubMed), Dimensions, and OpenAlex was conducted from inception to February 11, 2026. Studies reporting the prevalence of microorganisms in AFS (minimum 10 cases) from pregnant women with AFS diagnosed via transvaginal ultrasound were included. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment, with a third reviewer resolving discrepancies. Random-effects meta-analysis of proportions was used to pool overall and pathogen-specific prevalence. Four studies comprising 85 women met inclusion criteria. The pooled prevalence of any microorganism was 35% (95%CI 22-48%), with moderate heterogeneity (I2 = 36.8%). Ureaplasma spp. were the most frequently detected pathogens (pooled prevalence 17%, 95%CI 8-27%). Sensitivity analysis revealed that sampling technique was a source of heterogeneity in this dataset; excluding the single study using transvaginal amniocentesis reduced the pooled prevalence to 28% (95%CI 17-41%) and eliminated statistical heterogeneity (I2 = 0.0%). Transvaginally collected samples exhibited significantly greater microbial diversity (median 2 vs. 1 microorganism/sample, p = 0.005) and contained vaginal commensals, suggesting possible contamination. In transabdominal cohorts, the pooled prevalence of microorganisms (any) in amniotic fluid sludge was 28% (95%CI 17-41%), with Ureaplasma spp. emerging as the predominant pathogen when an infectious agent was identified. Transvaginal amniocentesis resulted in greater microbial diversity and detection of vaginal commensals, consistent with contamination. Our findings suggest that transabdominal sampling should be the preferred methodological approach for future studies of AFS microbiology.
We explored the possibility of antioxidant and antifibrotic effects of panthenol (PL) associated with modulation of coenzyme A (CoA) biosynthesis in the liver in a rat model of chronic obstructive cholestasis induced by bile duct ligation (BDL). We found that PL increased alcohol dehydrogenase (ADH) activity in the liver of BDL rats. PL and its analog pantethine increased pantothenate kinase (PANK) activity, restored hepatic CoA levels reduced by BDL, lowered protein-bound CoA, and normalized impaired mitochondrial functions associated with induced oxidative stress after BDL. These effects were accompanied by decreased collagen deposition and improved morphological features of hepatocytes. In contrast, PANK inhibitor, hopantenic acid (HPA), reduced hepatic CoA levels, aggravated hepatocellular damage, and promoted fibrosis. In the human hepatic stellate cell line LX-2, PL exhibited no cytotoxicity over a wide concentration range, increased intracellular CoA levels, decreased reactive oxygen species (ROS) production, and attenuated collagen accumulation associated with oxidative stress in vitro. Importantly, inhibition of ADH by 4-methylpyrazole completely abolished the protective effects of panthenol, indicating that its activity depends on metabolic pathways involving CoA. Notably, PL did not directly reduce H2O2 or superoxide anion radical production in cell-free systems but significantly suppressed lipid peroxidation in liposomes and red blood cells in vitro. Ultimately, these findings indicate that the antioxidant and antifibrotic effects of PL are associated with modulation of CoA metabolism and enhanced resistance of biological membranes to oxidative damage.
TRPM4 is a member of transient receptor potential (TRP) ion channel group which greatly contributes to cardiomyocyte function and physiology. It controls the dynamic stabilization of calcium level and is involved in sinus node regulation and cardiac conduction. Most of pathogenic variants in TRPM4 gene are associated with conduction disorders and various types of arrhythmic syndromes presenting in children and early adolescents. In addition, TRPM4 gain- and loss-of-function variants are discussed in connection to Brugada syndrome and long QT-syndrome. In this review we summarize current knowledge on the role of TRPM4 variants in pediatric arrhythmic syndromes, discuss molecular mechanisms of TRPM4 dysfunction, provide clinical illustrations and case presentations underlining the role of TRPM4 in molecular pathogenesis of arrhythmic syndromes presented in young age.
This study evaluates the diagnostic performance of two-dimensional (2D) microvascular flow imaging combined with standardized ultrasound markers for predicting placenta accreta spectrum disorders in pregnancies complicated by placenta previa or low-lying placenta. This prospective observational study included 61 women with placenta previa or low-lying placenta who underwent cesarean delivery between 32 and 38 weeks of gestation. All participants underwent standardized 2D microvascular flow imaging using the Samsung Hera W10 Elite system. The microvascular vascularization index was quantified as the percentage ratio of color-coded vascular pixels within a defined placental region of interest. Conventional Doppler indices and standardized ultrasound markers associated with placenta accreta spectrum were recorded. Placental invasion was confirmed histopathologically in 23 patients. Statistical analyses included Mann-Whitney U-testing, receiver operating characteristic (ROC) analysis, 95% confidence interval estimation, pairwise ROC comparison using the DeLong method, and exploratory internally validated machine-learning classification models. To avoid conceptual overlap and double counting, the total placenta accreta spectrum (PAS)score was excluded from the corrected machine-learning models. Intraobserver reproducibility of repeated MVI measurements was assessed using the intraclass correlation coefficient. The vascularization index was significantly higher in PAS cases than controls (47.65 ± 9.35 vs. 26.58 ± 8.93, P < 0.001). Conventional Doppler parameters did not differ significantly between groups. ROC analysis identified the vascularization index as the strongest single quantitative predictor of PAS, with an AUC of 0.985, sensitivity of 95.7%, and specificity of 97.4% at a cut-off value of 37.11. The corrected Placental Invasion Risk Score, calculated without the total PAS score, showed excellent diagnostic performance, with an AUC of 0.998. Exploratory machine-learning models excluding the total PAS score demonstrated improved discrimination after inclusion of the vascularization index, with logistic regression achieving an AUC of 0.990. Intraobserver reproducibility of repeated MVI measurements was excellent, with an intraclass correlation coefficient (ICC) of 0.977. For prediction of cesarean hysterectomy, the vascularization index also demonstrated excellent discriminatory performance at an optimal cut-off value of ≥53.51. The 2D MV-Flow vascularization index is a strong quantitative biomarker for predicting PAS in pregnancies complicated by placenta previa or low-lying placenta. When combined with individual ultrasound markers, but not redundantly with the total PAS score, it may improve antenatal risk stratification and preoperative planning. However, the exploratory machine-learning findings require external validation in larger multicenter cohorts.
To examine equity and respectful care for women and infants from five perspectives: the global context; economic issues; healthcare systems; legal and policy issues; opportunities to benefit from biomedical research. Narrative review. Healthcare accounts for half the variance in health in low-income countries and substantially less in high-income settings; however, healthcare investment remains efficient and equitable. Gross Domestic Product (GDP) affects women and infants disproportionately. Women undertake the major proportion of domestic and childcare duties including breastfeeding as unremunerated labour. This is not factored into GDP, so they do not benefit from growth-promoting incentives. Many countries do not provide adequate paid parental leave, nor the option of sharing leave with the non-birthing parent, despite their positive impacts on infant wellbeing and family cohesion with economic benefits. The rights of infants have received little attention. Women and infants have less opportunities to benefit from biomedical preclinical, translational, and population research. Only one medicine has been developed specifically for a neonatal disease (surfactant). Inequity and disrespect to mothers and infants is a barrier to human progress. Recognising the problem and developing policies and legislation to ensure equitable and respectful care, as well as monitoring effectiveness, are extremely important.
Objective: Isolated gestational proteinuria (IGP) has traditionally been considered a benign condition; however, emerging evidence suggests that it may represent an early stage in the spectrum of preeclampsia. This study aimed to evaluate clinical and laboratory predictors of progression from IGP to preeclampsia. Methods: This retrospective cohort study included pregnant women diagnosed with proteinuria ≥ 300 mg/day after 20 weeks of gestation between January 2023 and December 2024. After applying predefined exclusion criteria, 319 women with isolated gestational proteinuria (IGP) were included and stratified according to progression to preeclampsia (n = 42, 17.8%). Baseline clinical and laboratory parameters were compared between groups. Multivariable logistic regression analysis was performed to identify independent predictors of progression, and receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative performance of significant variables. Results: Preeclampsia developed in 17.8% of women with IGP. In multivariable analysis, higher maternal body mass index (aOR 1.085, p = 0.028) and earlier gestational age at diagnosis (aOR 0.883, p = 0.011) were identified as independent predictors of progression. Although neutrophil count and systemic inflammatory indices were elevated in univariate analyses, they did not retain independent predictive value after adjustment. Conclusions: In pregnancies complicated by isolated gestational proteinuria, clinical parameters appear to be more informative than inflammatory and renal markers for predicting progression to preeclampsia. Laboratory-derived indices offer limited additional value and should be interpreted cautiously in risk assessment.
Breast cancer (BC) is a complex, clinically and morphologically heterogeneous disease for which integral morphological and molecular genetic parameters are of key importance. This paper describes the evolution of semiquantitative tumor grading systems, beginning with the classical Greenough, Patey-Scarff, and Bloom-Richardson systems and ending with modern mathematical methods based on the grade of BC malignancy. Integral prognostic indices are presented in detail, including the Nottingham Prognostic Index (NPI), its modifications (NPI+, METASTASIS), the Total malignancy score (TMS), as well as new digital models and artificial intelligence algorithms predicting lymph node metastasis (LN) and response to therapy. The advantages of these indices in risk stratification and treatment selection are highlighted, as are their limitations related to tumor heterogeneity, dependence on research methods, and the need for integration with molecular genetic testing and digital technologies to further improve a personalized approach to breast cancer patient care. The following open scientific online resources were used to search for literature sources: PubMed, eLibrary, and the National Library of Medicine. Sources were selected using keywords (indicated in the appropriate field) and publication dates. Рак молочной железы (РМЖ) представляет собой сложное, клинически и морфологически гетерогенное заболевание, для которого ключевое значение имеют интегральные морфологические и молекулярно-генетические параметры. В работе описана эволюция полуколичественных шкал градации опухоли, начиная с классических систем Greenough, Patey—Scarff и Bloom—Richardson и заканчивая современными математическими методами, в основе которых лежит степень злокачественности РМЖ. Подробно представлены интегральные прогностические индексы, включая ноттингемский прогностический индекс (НПИ), его модификации (НПИ+, METASTASIS), суммарный балл злокачественности, а также новые цифровые модели и алгоритмы искусственного интеллекта, прогнозирующие метастатическое поражение лимфатических узлов и ответ на терапию. Отмечены преимущества данных индексов в стратификации риска и выборе тактики лечения, а также их ограничения, связанные с гетерогенностью опухоли, зависимостью от методов исследования, а также необходимостью интеграции с молекулярно-генетическими тестами и цифровыми технологиями для дальнейшего совершенствования персонализированного подхода к ведению пациенток с РМЖ. Для поиска источников литературы были использованы следующие открытые научные интернет-ресурсы: PubMed, eLibrary, National Library of Medicine. Отбор источников проводился по ключевым словам (указаны в соответствующем поле) и датам издания.
Objective: To evaluate and compare fetal arterial and venous Doppler parameters in early-onset (EO) and late-onset (LO) fetal growth restriction (FGR), and to assess their performance within the study cohort and their association with composite adverse neonatal outcome (CANO). Methods: This prospective observational cohort study included 184 singleton pregnancies between 24 and 37 weeks of gestation, comprising 91 FGR cases and 93 appropriate-for-gestational-age controls. FGR was defined according to Delphi consensus criteria and classified as EO-FGR (<32 weeks) or LO-FGR (≥32 weeks). All fetuses underwent standardized Doppler assessment of the umbilical artery (UA), middle cerebral artery (MCA), uterine artery (UtA), and ductus venosus (DV). The cerebroplacental ratio (CPR) was calculated. Multivariable logistic regression models were constructed separately for EO-FGR and LO-FGR. Classification performance was evaluated using receiver operating characteristic analysis. CANO was defined as at least one of the following: 5-min Apgar score <7, respiratory distress syndrome, neonatal intensive care unit admission, or preterm birth. Results: In both EO-FGR and LO-FGR, UA PI values were significantly higher, whereas MCA PI and CPR were significantly lower than in controls. CPR demonstrated the highest discriminative performance among arterial parameters in both subgroups. DV Doppler indices were not significantly different in EO-FGR. In LO-FGR, DV S-wave and v-wave velocities were independently associated with FGR. No significant associations were observed between Doppler parameters and CANO in subgroup analyses. Conclusions: Arterial Doppler parameters, particularly CPR, showed consistent alterations in both EO- and LO-FGR. The contribution of venous Doppler parameters differed according to clinical subtype, with additional value observed in LO-FGR.
Backgroud and Objectives: To evaluate conventional Doppler indices and the novel middle cerebral artery (MCA) diastolic deceleration area (DDA) in pregnancies complicated by gestational diabetes mellitus (GDM), and to explore their associations with perinatal outcomes. Prospective case-control study conducted at a tertiary referral perinatology center. Materials and Methods: The study included 83 women with GDM and 92 healthy controls. Standard fetal biometric and Doppler parameters-umbilical artery, MCA, ductus venosus, cerebroplacental ratio, and umbilicocerebral ratio-were assessed, alongside calculation of MCA DDA. Perinatal outcomes were recorded. Results: Most conventional Doppler indices did not differ between groups, except for lower MCA dicrotic notch velocity and higher ductus venosus time-averaged maximum velocity in the GDM group. MCA DDA values did not differ significantly between GDM and control groups (6.67 [5.02-8.20] vs. 7.05 [5.21-8.39] cm·s, p = 0.444) and showed no difference between insulin- and diet-controlled subgroups (p > 0.05). MCA DDA showed significant correlations with gestational age, MCA peak systolic velocity, and birth weight. However, after adjustment for potential confounders, gestational age remained the only independent determinant of MCA DDA. The multivariable analysis evaluating composite adverse neonatal outcomes was limited by the small number of adverse events (n = 14). Conclusions: MCA DDA did not differ between GDM and control pregnancies and primarily reflected gestational age-related physiological variation rather than diabetes specific hemodynamic changes. However, its relationship with adverse neonatal outcomes remains uncertain and requires further investigation in larger prospective studies.
Background/Objectives: Term and preterm premature ruptures of membranes (PROM and PPROM) are serious pregnancy complications associated with adverse maternal and neonatal outcomes. Although widely studied in the global literature, data on the risk factors and outcomes of PROM and PPROM in the Middle East and North Africa (MENA) region remain limited. This mapping review aimed to identify and assess existing evidence and highlight gaps in knowledge regarding risk factors for PROM, including preterm PROM, and related maternal and neonatal outcomes among women in the region. Methods: We conducted a comprehensive and systematic search of articles published in English and Arabic between January 2000 and June 2025 across Scopus, Embase, Web of Science, and PubMed/Medline. Eligible studies included observational and interventional studies conducted in MENA countries. Data were extracted and synthesised using thematic mapping. Results: Out of 5359 retrieved records, 136 met the inclusion criteria. The main study design was cross-sectional (51 studies), followed by case-control (41), cohort (26), and 15 randomised controlled trials. The geographic distribution of the evidence varied significantly. Research has mainly focused on PROM and its biological risk factors, such as infections and chronic medical conditions. Psychological and environmental factors have been the least reported. Neonatal and gestational outcomes have frequently been addressed, whereas maternal outcomes have received less attention. Conclusions: The findings reveal significant geographic, thematic, and methodological disparities in research throughout the MENA region. The results underscore the need for further studies on the prevention and identification of women at higher risk of PROM.
In this study, it was aimed to evaluate fetal arterial and venous Doppler parameters and to assess their association with adverse obstetric outcomes by focusing on the amniotic fluid volume and glycemic status of pregnant women. A prospective study was conducted at a tertiary care center from August 2022 to July 2024, including 171 participants divided into four groups: control (normal amniotic fluid, n = 47), idiopathic polyhydramnios (n = 42), gestational diabetes mellitus (GDM) with polyhydramnios (n = 42), and GDM with normal amniotic fluid (n = 40). Doppler ultrasonography was performed to measure arterial parameters, including middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (UtA), and venous parameters, including pulmonary vein (PV), inferior vena cava (IVC), and ductus venosus (DV). Composite adverse perinatal outcomes (CAPO) were analyzed. MCA S/D ratio and pulsatility index (PI) were significantly elevated in both GDM groups (p < 0.001), while UA and UtA parameters showed no significant differences between the groups. Venous Doppler parameters, including PV, IVC, and DV, did not correlate significantly with CAPO. The hepatic vein S/D ratio demonstrated a borderline significant increase in the idiopathic polyhydramnios group (p = 0.041). Although certain adverse neonatal outcomes, such as transient tachypnea of the newborn (TTN) and neonatal hypoglycemia, were more frequently observed in the GDM groups, no significant association was found between Doppler parameters and CAPO. Venous Doppler measurements demonstrated minimal utility in forecasting unfavorable neonatal outcomes, whereas MCA Doppler parameters showed modest discriminatory ability and may reflect altered fetal hemodynamics in GDM pregnancies; however, their clinical utility remains limited. These findings highlight the complexity of outcomes associated with polyhydramnios and underscore the need for larger prospective studies to improve risk prediction in high-risk pregnancies.
Inbred BALB/c mice were intragastrically administered with a new antitubercular compound macozinone (PBTZ169) or a combination of isoniazid, rifampicin, and pyrazinamide (HRZ) for six months; control animals received no antitubercular drugs. After 6 months, the microbiota of the large intestine was analyzed. Unlike HRZ combination, macozinone practically does not affect the microbiota: its composition remained the same as in the control group. In lung tissue, differences in the expression of some genes regulating the immune response were found. Two months post-infection with Mycobacterium tuberculosis, mice treated with either the HRZ combination or macozinone exhibited distinct immune responses to tuberculin.
Congenital diaphragmatic hernia (CDH) is a severe developmental defect characterized by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Fetoscopic endoluminal tracheal occlusion (FETO) is a prenatal intervention used in severe CDH to stimulate lung growth, yet its effects on fetal cardiac function remain insufficiently understood. This systematic review aimed to evaluate the impact of FETO on cardiac structure and function in fetuses with CDH. A comprehensive literature search identified four studies that met the inclusion criteria. Most studies were retrospective and showed considerable heterogeneity in study design. Overall, the available evidence suggests that FETO does not negatively affect fetal cardiac function and may promote favorable cardiac remodeling. Several studies reported improved growth of left-sided cardiac structures and better right ventricular performance in FETO-treated fetuses compared with severity-matched controls. Given the limited number of studies and their methodological variability, these findings should be interpreted with caution. Further well-designed, prospective studies with standardized cardiac assessment protocols and clearly defined outcome measures are needed to better characterize the cardiovascular effects of FETO in CDH.
To assess if aspirin dosed based on a patient's body mass index (BMI) would yield similar pharmacokinetics and pharmacodynamics for obese compared to non-obese patients who are taking aspirin to prevent preeclampsia. This prospective cohort study included 35 pregnant women at high-risk of developing preeclampsia from Haseki Training and Research Hospital, Istanbul, Türkiye. Participants were prospectively stratified (non-randomized) into two groups based on baseline BMI: Group 1 (n = 17, BMI <30 kg/m2, 100 mg/day aspirin) and Group 2 (n = 18, BMI ≥30 kg/m2, 150 mg/day aspirin). Blood salicylate levels, 11-dehydrothromboxane B2 (11-dTxB2) levels, uterine artery Doppler measurements, and diastolic notch presence were evaluated at both the baseline (weeks 12-16 of pregnancy) and follow up (weeks 16-20 of pregnancy). Biomarker analyses were available for 17 of 18 obese participants due to one missing sample. Although the obese group was administered 50% more aspirin, they had 17% lower serum salicylate levels at follow-up (mean ± SD 2.08 ± 0.23 vs. 2.52 ± 0.32 μg/mL, p < 0.001). Although the 100 mg group had a significant decrease in 11-dTxB2 (p = 0.004), the 150 mg group did not have a significant decrease (p = 0.379). BMI had a strong inverse correlation with salicylate levels (r = -0.648, p < 0.001). A multiple regression model was developed using study group (β = 16.368, p = 0.002) and BMI (β = -1.984, p = 0.003) as the independent variables, and the uterine artery resistance index (UtA-RI) as the dependent variable. Mediation analysis showed that 21.0% of the total effect was numerically attributable to salicylate levels; however, the indirect effect was not statistically significant (Sobel p = 0.524). Uterine artery resistance change was the most significant predictor of diastolic notch resolution (OR = 0.86, p = 0.009). In this non-randomized cohort, a 150 mg aspirin dose did not appear to overcome the pharmacokinetic and pharmacodynamic disadvantages associated with obesity in pregnant women. Other dosing approaches, such as weight-based dosing or twice-daily administration, should be evaluated to optimize preeclampsia prophylaxis in obese pregnancies. These findings require confirmation in larger randomized trials.
Biosecurity threats are issues of public health importance because of their implications for global health security. Although some strategies have been implemented by global organizations to mitigate risks from natural, accidental, or deliberate biological threats, empirical data on global health preparedness for biosecurity threats generally are still evolving. Hence, this study aimed to synthesize existing evidence of the role of emerging technologies in enhancing global health preparedness for biosecurity threats. Using a PRISMA-guided protocol, we conducted a systematic review of (peer-reviewed) published and grey articles regarding biosecurity preparedness and emerging technologies in PubMed, Google Scholar, and EBSCOHOST from 2015 to 2026. Extracted data were used for narrative synthesis. Most relevant and representative 51 out of a total of 349 identified papers were selected and reviewed for this study. Key technologies identified include artificial intelligence, genomic surveillance, synthetic biology, biosensors, robotics, and digital health platforms. These technologies improve outbreak detection, surveillance, and response coordination. However, challenges include dual-use risks, ethical concerns, inequitable access, and regulatory gaps. We conclude that emerging technologies offer great prospects for enhancing global health preparedness but require robust governance frameworks, equitable access, and interdisciplinary collaboration to mitigate risks and maximize benefits. A multidisciplinary approach involving synergy between relevant stakeholders is required to combat biosecurity threats, as the world has become a global village through advances in technology.
This study aimed to compare the efficacy of administering carbetocin before versus after placental delivery in preventing PPH in low-risk vaginal deliveries. The randomized controlled trial was conducted at Kartal City Hospital, Istanbul, Turkey. A total of 160 primiparous women with uncomplicated pregnancies who underwent vaginal delivery were enrolled. Participants were randomly assigned to receive 100 mcg of carbetocin either before or after placental delivery. The primary outcome was the incidence of PPH. Secondary outcomes included the need for additional uterotonics, manual removal of the placenta with consequent antibiotic administration, blood transfusions, maternal adverse events, and changes in hemoglobin levels at baseline and 24 h postpartum. The incidence of PPH was significantly lower in the carbetocin-before group than in the carbetocin-after group (p=0.015). The carbetocin-before group had a significantly lower mean hemoglobin drop compared to the carbetocin-after group (p<0.001). The need for additional uterotonics was significantly higher in the carbetocin-after group (p<0.001). Manual placenta removal and the need for antibiotics were more frequent in the carbetocin-before group (p=0.017). No significant differences in adverse maternal events were observed between the groups. Administering carbetocin before placental delivery significantly reduces the incidence of PPH, blood loss, and the need for additional uterotonics. However, the increased rate of manual placenta removal necessitates individualized risk-benefit assessment; pre-placental administration may be most advantageous in women at elevated risk for PPH, in whom the hemorrhagic benefit outweighs the risks associated with manual extraction.