Adverse pregnancy outcomes (APOs), including preterm birth, preeclampsia, low birth weight, recurrent miscarriage, gestational diabetes mellitus, and fetal growth restriction, remain major threats to maternal and offspring health. Increasing evidence links the maternal microbiome to pregnancy health, but most studies have examined individual microbial niches rather than their interactions. The oral cavity and gut are anatomically and immunologically connected and form a bidirectional oral-gut microbiota axis through microbial trafficking, immune signaling, and metabolite-mediated feedback. Emerging studies suggested that oral dysbiosis, periodontal inflammation, and gut microbial remodeling were associated with APOs, although direct causal evidence in human pregnancy remains limited. This review summarizes pregnancy-related remodeling of the oral-gut microbiota axis, evaluates clinical and experimental evidence linking oral and gut dysbiosis to APOs, and discusses potential mechanisms, including microbial translocation, immune and inflammatory activation, metabolic remodeling, epigenetic regulation, and outer membrane vesicle-mediated signaling. Candidate biomarkers, probiotic and dietary intervention strategies, and current translational limitations are also discussed. Overall, the oral-gut microbiota axis offers a useful framework for understanding microbiome-associated APOs, but standardized sampling, longitudinal cohorts, and mechanistic validation are required before clinical application.

Background/Objectives: Hallux valgus is a common forefoot deformity whose surgical correction generally yields favorable functional outcomes. However, postoperative complications remain a clinically relevant concern, and the contribution of preoperative risk factors has not been comprehensively characterized in the context of the Spanish population. This study aimed to analyze the relationship between preoperative risk factors and the occurrence of complications after hallux valgus surgery, and to assess whether their accumulation follows a dose-response pattern of increased postoperative risk. Methods: A retrospective observational study was conducted in 123 consecutive patients who underwent hallux valgus surgery between 1 January 2017 and 31 December 2018, with a mean follow-up of 12 months. Variables analyzed included age, sex, deformity severity, active smoking, diabetes mellitus, and antiplatelet or anticoagulant therapy. An accumulated risk factor index based on three clinical risk factors was constructed. Statistical analysis included descriptive statistics, the Cochran-Armitage trend test, and multivariate logistic regression. Results: The mean age was 57.4 years; 82.1% were female. Active smokers accounted for 31.7%, 14.6% had diabetes mellitus, and 13.0% were receiving antithrombotic therapy. The overall complication rate was 20.3%, comprising recurrence (12.2%), chronic residual pain (6.5%), joint stiffness (4.1%), and infection (4.1%). Complication frequency increased progressively from 15.9% in patients without risk factors to 50.0% in those with three concurrent factors (p-trend = 0.038). In multivariate analysis, male sex (odds ratio [OR] 5.39; 95% confidence interval [CI] 1.41-21.19; p = 0.014) and diabetes mellitus (OR 8.37; 95% CI 1.42-63.60; p = 0.026) were independently associated with a higher risk of complications. Conclusions: Hallux valgus surgery generally has a favorable prognosis; however, the presence of preoperative risk factors significantly influences postoperative risk. Diabetes mellitus and the accumulation of risk factors identify patients who could benefit from more rigorous preoperative evaluation, metabolic optimization, and closer postoperative follow-up.

Background: Coronary in-stent restenosis (ISR) remains a major limitation of percutaneous coronary intervention (PCI) with drug-eluting stents (DES), adversely affecting long-term outcomes. Most available prediction models rely on invasive procedural variables and have been developed predominantly in high-income populations, limiting their generalizability. This study aimed to identify independent predictors of coronary ISR and to develop and internally validate a clinically applicable risk stratification model based on routinely available clinical, laboratory, and procedural factors in a cohort of patients from Kazakhstan. Methods: In this retrospective case-control study, 910 patients with coronary artery disease (CAD) who underwent follow-up coronary angiography after PCI between January 2018 and July 2025 were included. The study comprised 455 patients with angiographically confirmed coronary in-stent restenosis and 455 patients without restenosis selected using a consecutive sampling approach. Clinical characteristics, laboratory parameters, echocardiographic findings, and angiographic data were analyzed. Independent predictors were identified using multivariable binary logistic regression. Model discrimination was assessed using receiver operating characteristic (ROC) curve analysis, and internal validation was performed using bootstrap resampling. Results: The mean age was 62.9 ± 8.9 years, and 75.2% of patients were male. Restenosis was independently associated with prior myocardial infarction (MI) (OR 2.20; 95% CI 1.65-2.80), type 2 diabetes mellitus (T2DM) (OR 2.60; 95% CI 1.93-3.47), and smoking (OR 1.40; 95% CI 1.01-1.89). Patients with restenosis demonstrated a less favorable inflammatory and metabolic profile, including higher NLR, MHR, atherogenic index, and TyG index (all p < 0.05). LVEF was significantly lower, while multivessel disease and the number of implanted stents was higher (p < 0.001). A risk stratification model incorporating T2DM, the number of implanted stents, MPV, neutrophil count, HDL-C, LVEF demonstrated good discrimination (AUC 0.828) and 74.4% accuracy. Conclusions: The proposed model demonstrated good discrimination and satisfactory internal validity with limited optimism after internal bootstrap validation. It may serve as a useful tool for patient risk stratification after PCI. External validation in independent cohorts is required before widespread clinical implementation.

Background/Objectives: Type 2 diabetes mellitus (DM) and carotid atherosclerosis are established risk factors for cardiovascular disease (CVD). However, their relative and combined prognostic significance in individuals without known CVD remains uncertain. This study aimed to evaluate the independent and combined associations of carotid plaques and DM with cardiovascular events and mortality in a high-cardiometabolic-risk primary prevention cohort. Methods: This prospective cohort study followed 6138 participants (3571 men [57%] and 2567 women [43%]; median age 53 years, IQR 48-58) enrolled in the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program from 2006 to 2023. All individuals underwent clinical assessment and carotid ultrasonography. Participants were stratified by DM status and the presence of carotid plaques. Associations with cardiovascular events, major adverse cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death), and all-cause mortality were evaluated using Cox proportional hazards models. Results: During follow-up (median 6.5 years, IQR 4.5-9.0), 954 participants (16%) experienced composite cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death). Bilateral carotid plaques were more common in individuals with cardiovascular events (23.3% vs. 19.4%; p = 0.007). Individuals with both DM and carotid plaques had the highest risk of MACE (HR = 1.696; 95% CI: 1.346-2.136; p < 0.001), myocardial infarction (MI; HR = 4.089; 95% CI: 1.590-10.516; p = 0.003), and all-cause mortality (HR = 1.802; p = 0.015). The presence of carotid plaques without DM was independently associated with increased risk of MACE (HR = 1.234; 95% CI: 1.062-1.433; p = 0.006) and MI (HR = 2.492; 95% CI: 1.176-5.278; p = 0.017), but not all-cause mortality (HR = 0.986; 95% CI: 0.689-1.413; p = 0.941). In contrast, DM without carotid plaques was not significantly associated with any outcome examined. Conclusions: In this high-cardiometabolic-risk primary prevention cohort, carotid plaques were independently and more strongly associated with cardiovascular outcomes than diabetes alone. Individuals with both carotid plaques and diabetes showed the highest observed risk of adverse cardiovascular events and all-cause mortality. These findings are associational and apply to a high-risk metabolic syndrome cohort; extrapolation to the general population requires further study. The results support the prognostic value of carotid plaque assessment as an adjunctive tool in cardiovascular risk evaluation.

Background/Objectives: Patients receiving a cardiac implantable electronic device (CIED) for conduction disease may remain at substantial long-term risk despite preserved systolic function at implantation. The prognostic association of sodium-glucose cotransporter-2 (SGLT2) inhibitor use in this population is uncertain. We therefore examined the relationship between early documented SGLT2 inhibitor use and subsequent all-cause mortality in patients with preserved left ventricular ejection fraction (LVEF) undergoing CIED implantation for conduction disease. Methods: In this retrospective single-center cohort study, we screened consecutive adults who underwent CIED implantation for conduction disease between January 2018 and June 2024. Patients with LVEF ≥ 50% and complete clinical, laboratory, electrocardiographic, and echocardiographic data were included. SGLT2 inhibitor exposure was defined as documented initiation or active use within 3 months after implantation. The primary endpoint was all-cause mortality. Associations were evaluated using multivariable Cox proportional-hazards regression and Kaplan-Meier analyses. Results: Among 2176 screened patients, 540 fulfilled the eligibility criteria, of whom 206 (38.1%) had documented SGLT2 inhibitor exposure. During a median observation period of 64.2 months (range, 7-90 months), 185 deaths occurred. SGLT2 inhibitor exposure was associated with a lower adjusted hazard of death (HR, 0.48; 95% CI, 0.38-0.69; p < 0.001). Survival also differed between exposure groups in the overall cohort (log-rank p = 0.006) and in patients without either heart failure or diabetes mellitus (log-rank p = 0.020). Conclusions: In patients with preserved LVEF undergoing CIED implantation for conduction disease, documented SGLT2 inhibitor use was independently associated with lower all-cause mortality. These observational findings are hypothesis-generating and warrant confirmation in prospective studies.

Background/Objectives: This population-based observational study with a repeated cross-sectional design included singleton live births occurring in Tuscany, Italy, between 2010 and 2021, identified through regional Delivery Assistance Certificates (CeDAP) and linked with administrative healthcare databases. The study aimed to assess temporal trends in the prevalence of gestational diabetes mellitus (GDM) and to evaluate the contribution of major risk factors-particularly pregestational obesity, maternal age, parity, and origin from high-pressure migration countries (HPMC)-to GDM and related maternal-neonatal outcomes. The rationale for the study derives from the increasing worldwide prevalence of GDM, driven by changes in diagnostic criteria as well as evolving maternal demographic and metabolic risk profiles. Methods: The study included 266,394 singleton live births. GDM was identified using a previously validated algorithm based on insulin prescriptions, diabetes specialist visits, attendance to education programs, and postpartum oral glucose tolerance testing. Temporal trends in GDM, pregestational obesity, HPMC origin, and maternal-neonatal outcomes were assessed. Multivariable Poisson regression models with robust variance estimation were used to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for GDM and adverse outcomes, including preterm birth, macrosomia, neonatal distress, and cesarean delivery. Results: During the study period, the annual number of births declined, whereas the overall mean prevalence of GDM was 11.37% and increased steadily from 8.23% in 2010 to 14.43% in 2021, corresponding to a relative increase of approximately 75%. Pregestational obesity and pregnancies among women from HPMC also increased over time. Multivariable analysis showed that pregestational obesity, advanced maternal age, multiparity, and HPMC origin were major independent determinants of GDM. Pregestational obesity emerged as the most important variable associated with both GDM and maternal-neonatal complications, including macrosomia, cesarean delivery, and neonatal distress, often showing stronger associations than GDM itself. Macrosomia and cesarean delivery declined over time, whereas preterm birth increased among pregnancies complicated by GDM. An inverse association between GDM and fetal macrosomia was observed in adjusted models, possibly reflecting effective clinical management, earlier delivery strategies, or algorithm-related selection effects. Conclusions: GDM prevalence increased substantially in Tuscany between 2010 and 2021 despite declining birth rates. This increase appears to be mainly associated with rising pregestational obesity, older maternal age, multiparity, and changes in population composition related to migration from HPMC. Adverse maternal-neonatal outcomes were more strongly associated with pregestational obesity and maternal age than with GDM itself, suggesting that preventive strategies targeting metabolic health before pregnancy may be crucial for reducing both GDM and related complications. Monitoring temporal trends in GDM and its risk factors may also serve as an indirect indicator of the effectiveness of regional healthcare policies.

Background. Cardiometabolic diseases are the leading cause of morbidity and mortality worldwide and are driven by risk factors such as hypertension, diabetes mellitus, and dyslipidemia. Early vascular aging (EVA) is a pathological process characterized by accelerated arterial stiffness and endothelial dysfunction, which increase the risk of cardiovascular events. Key markers of EVA include advanced glycation end products (AGEs), aortic pulse wave velocity (a-PWV), glycated hemoglobin A1c (HbA1c) and pulse pressure (PP). Although these markers are individually associated with cardiovascular outcomes, there is still limited evidence from longitudinal studies evaluating their combined association with cardiometabolic diseases and hypertension, particularly with consideration of gender differences. Therefore, in this study, data from the two-year EVasCu cohort were used to analyze the associations between EVA and cardiometabolic diseases and hypertension; the associations between EVA related parameters (AGEs, a-PWV, HbA1c and PP) were evaluated, and these associations were assessed by gender. Methods. AGE, a-PWV, HbA1c and PP were measured as indicators of EVA, in addition to sociodemographic and clinical variables. Logistic regression was applied to assess the association between EVA and cardiometabolic diseases (including hypertension, diabetes mellitus, acute myocardial infarction (AMI), dyslipidemia, angina pectoris, and heart failure (HF)) and hypertension, adjusting for age, gender and risk factors. Results. A 2-year longitudinal study was conducted with 200 adults in Cuenca, Spain. EVA was significantly associated with the development of cardiometabolic diseases (OR = 1.38; p = 0.028) and hypertension (OR = 1.63; p = 0.015), which was more pronounced in females. Cardiometabolic diseases and hypertension were associated with a-PWV and PP, but not with AGEs or HbA1c. Conclusions. a-PWV and PP are predictors of cardiometabolic diseases and hypertension, especially in females. Early detection and preventive strategies are essential for detecting cardiovascular risk and mitigating consequences. Further studies are needed to investigate the relationships between EVA and cardiometabolic factors.

Objectives: To investigate the relationship between intrapartum cardiotocography (CTG) findings and neonatal outcomes by evaluating the association between CTG tracings, umbilical cord blood gas parameters, and APGAR scores, and to assess the diagnostic performance of CTG in identifying fetuses at risk of neonatal acidemia. Methods: This prospective study included women who delivered at a tertiary teaching hospital between January 2017 and January 2018. Of 1100 women initially screened, 596 met the inclusion criteria and were analyzed. Among them, 162 underwent operative delivery for non-reassuring fetal status (NRFS), while 434 served as controls. Demographic, obstetric, and neonatal characteristics were compared. Multivariable logistic regression was performed to explore factors associated with umbilical arterial pH < 7.20. Results: Mean umbilical arterial pH was significantly lower in the NRFS group than in controls (7.30 ± 0.08 vs. 7.32 ± 0.07, p < 0.05). Umbilical arterial pH differed significantly across NICHD fetal heart rate categories, with the highest values observed in Category I tracings. Twenty-eight neonates (4.7%) had an umbilical arterial pH < 7.20. CTG-based identification of NRFS predicted umbilical arterial pH < 7.20 with a sensitivity of 42.9%, specificity of 73.6%, positive predictive value of 7.4%, and negative predictive value of 96.3%. In multivariable analysis, pregestational diabetes mellitus and preeclampsia were independently associated with umbilical arterial pH < 7.20. Conclusions: Although CTG remains an essential tool for intrapartum fetal surveillance, its low positive predictive value indicates that many fetuses classified as having NRFS do not have biochemical evidence of acidemia. CTG findings should therefore be interpreted together with the overall clinical context, including maternal risk factors such as pregestational diabetes mellitus and preeclampsia, rather than being used in isolation to guide intrapartum management.

Background/Objectives: Intensive care unit (ICU) mortality reflects interactions between baseline vulnerability, acute physiological derangement, ICU-acquired infection, and the intensity of organ-support therapy. Methods: This single-center retrospective cohort study included 3323 adult first ICU hospitalizations at the University Clinical Hospital in Bialystok, Poland, between 1 January 2017 and 1 June 2023. Secondary ICU admissions/readmissions, patients aged <18 years, and one pregnancy admission were excluded. Patients were classified as ICU survivors (n = 1778) or ICU non-survivors (n = 1545). Variables were compared using t-tests, chi-square tests, or Fisher exact tests, and an adjusted logistic regression model was fitted as an exploratory prognostic model. Results: ICU mortality was 46.5%, and 28-day ICU mortality was 40.2%. Non-survivors were older than survivors (66.7 ± 15.1 vs. 60.9 ± 17.2 years; p < 0.001) and more frequently had arterial hypertension, diabetes mellitus, COVID-19, ischemic heart disease, atrial fibrillation, renal failure, and acute myocardial infarction or ischemic stroke. In the adjusted model, ICU mortality was associated with age per 10 years (OR 1.32, 95% CI 1.18-1.47), COVID-19 (OR 3.15, 95% CI 2.07-4.79), ventilator-associated pneumonia (OR 1.68, 95% CI 1.22-2.30), lactate per 1 mmol/L (OR 1.29, 95% CI 1.16-1.43), pH per 0.1-unit decrease (OR 1.79, 95% CI 1.41-2.29), mechanical ventilation (OR 14.74, 95% CI 3.40-63.87), cardiopulmonary resuscitation (OR 9.45, 95% CI 4.67-19.13), renal replacement therapy (OR 2.01, 95% CI 1.39-2.91), and treatment of acidosis or alkalosis (OR 1.95, 95% CI 1.29-2.94). Conclusions: ICU non-survival was associated with older age, COVID-19, cardiovascular and renal vulnerability, ICU-acquired infection, inflammatory and metabolic dysfunction, and early requirement for rescue organ-support interventions. These findings should be interpreted as adjusted associations, not causal effects.

Background/Objectives: Autonomous cortisol secretion (ACS), including mild autonomous cortisol secretion (MACS), nonfunctioning adrenal tumors (NFAT), and overt Cushing's syndrome (CS), is common in patients with adrenal incidentaloma (AI). Although ACS has been linked to adverse cardiometabolic outcomes, its association with renal function and electrolyte homeostasis has not been well characterized. To examine the associations of different degrees of ACS with renal function and serum electrolyte profiles in patients with AI. Methods: This retrospective single-center study included 575 adult patients with AI who underwent an overnight low-dose dexamethasone suppression test (LDDST). Patients were classified as having NFAT (n = 30), MACS (n = 236), or overt CS (n = 309) according to biochemical findings and clinical presentation. Clinical characteristics, hormonal parameters, estimated glomerular filtration rate (eGFR), and serum electrolyte levels were collected. Multivariable regression analyses were performed after adjustment for age, sex, tumor size, body mass index, hypertension, diabetes mellitus, smoking status, and alcohol consumption. Results: Compared with the NFAT and MACS groups, patients with overt CS were younger and predominantly female (84.5%), more frequently hypertensive, and had the highest serum and urinary free cortisol, the lowest ACTH, and the most pronounced electrolyte disturbances, with higher serum sodium and lower serum potassium (all p < 0.001). A pattern of electrolyte alterations was observed across the spectrum of cortisol autonomy (CS ≈ MACS > NFAT). Compared with NFAT, cortisol-secreting tumors were associated with higher serum sodium levels and lower serum potassium and calcium levels (p < 0.001). These associations remained significant after multivariable adjustment (p < 0.001). By contrast, although median eGFR differed among groups and tended to be higher in cortisol-secreting tumors, ACS was not significantly associated with clinically overt renal impairment based on categorical eGFR analysis. Conclusions: In patients with AI, increasing degrees of ACS are associated with alterations in electrolyte homeostasis, particularly involving sodium, potassium, and calcium. In contrast, no clear association was identified between ACS and clinically overt renal impairment in this cross-sectional cohort. Routine monitoring of electrolyte balance may be warranted in patients with cortisol-secreting adrenal tumors.