Search Results (1,452)

Background/Objectives: Traumatic brain injury (TBI) is increasingly understood as a chronic condition, but the role of early post-injury lifestyle behaviors in later cardiometabolic risk remains unclear. We examined whether lifestyle behaviors reported 1 year after injury were associated with the accumulation of common cardiometabolic risk factors by 5 years in the Traumatic Brain Injury Model Systems (TBIMS) National Database. Methods: This retrospective cohort secondary analysis included adults with followed 1-year and 5-year interviews, complete 1-year data on four behaviors, and the complete ascertainment of hypertension, diabetes or high blood sugar, and high cholesterol at both waves. The exposure was a favorable lifestyle count based on not smoking, non-heavy alcohol use, non-obese body mass index, and sports or exercise at least 10 times per month. The primary endpoint was the incident accumulation of at least two new common cardiometabolic conditions between years 1 and 5. The analytic cohort was an observed-data subset defined by follow-up retention, complete behavior data, paired outcome ascertainment, and baseline at-risk status rather than a random sample of all TBIMS participants. Results: Among 10,057 linked participants with followed interviews at both waves, 9593 were adults, 3182 had complete four-behavior exposure data, 689 had complete cardiometabolic ascertainment, and 581 formed the primary at-risk observed-data cohort. The primary endpoint occurred in 39 participants (6.7%). Each additional favorable behavior was associated with lower odds of the primary endpoint in the adjusted model (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.41–0.98; p = 0.040). The results were similar after adjustment for the 1-year Functional Independence Measure cognitive score and in Firth logistic regression. Because the final cohort was selected and the number of primary events was small, the estimates should be interpreted as exploratory and may not generalize to the broader TBI population. Conclusions: More favorable 1-year lifestyle profiles were associated with lower 5-year cardiometabolic risk factor accumulation after TBI. These findings support prevention-oriented follow-up but do not establish causality or validate a prognostic score. Full article

Background: Low-density lipoprotein cholesterol (LDL-C) is a central modifiable driver of atherosclerotic cardiovascular disease, yet cardiovascular risk in type 2 diabetes mellitus (T2DM) may be better captured by longitudinal LDL-C exposure than by a single LDL-C measurement. We examined the association of current LDL-C, cumulative LDL-C burden, and prior time below LDL-C targets with incident acute coronary syndrome (ACS) in patients with T2DM. Methods: We conducted a retrospective longitudinal cohort study using routinely collected electronic health-record data. Patients with T2DM and at least one valid LDL-C measurement between 1 January 2018 and 31 December 2023 were followed from the first eligible LDL-C measurement until incident ACS or administrative censoring on 31 March 2024. LDL-C was modeled using time-updated start–stop Cox regression. The primary exposure was current LDL-C category: <1.4, 1.4 to <1.8, 1.8 to <2.6, 2.6 to <3.4, 3.4 to <4.9, and ≥4.9 mmol/L. Secondary exposure metrics were cumulative LDL-C burden above prespecified thresholds and prior percentage of follow-up time below LDL-C targets. Models were adjusted for age, sex, hypertension, chronic kidney disease, HbA1c, T2DM duration, and calendar year of baseline LDL-C measurement; HbA1c and T2DM duration were multiply imputed. Results: The analytic cohort included 106,185 patients, 426,965 LDL-C intervals, and 5416 incident ACS events over 419,251.0 person-years. Compared with current LDL-C <1.4 mmol/L, adjusted ACS risk was higher for current LDL-C 3.4 to <4.9 mmol/L (HR 1.35, 95% CI 1.21–1.50) and ≥4.9 mmol/L (HR 1.94, 95% CI 1.63–2.32), whereas lower LDL-C categories were not clearly different from the reference category after adjustment. Each 1 mmol/L-year higher cumulative LDL-C burden was associated with higher ACS risk across evaluated thresholds, with HRs ranging from 1.04 to 1.13. Greater prior time below LDL-C targets was associated with lower ACS risk, with HRs of 0.97–0.98 per 10% higher time below target. Findings were consistent in sensitivity analyses restricted to patients with at least three LDL-C measurements, landmark analyses, and complete-case analysis. Conclusions: In patients with T2DM, incident ACS risk was associated with very high current LDL-C and with longitudinal LDL-C exposure captured by cumulative burden and time below target. These findings support sustained, target-oriented LDL-C control and suggest that longitudinal LDL-C metrics may complement single LDL-C values in cardiovascular risk assessment. Full article

Background: Oropharyngeal cancer (OPC) incidence has been increasing among males in the United States, reflecting a complex interplay among social, behavioral, and biological determinants of health. This study aimed to quantify cumulative risk profiles and their relationship with the burden of comorbid conditions in men with OPC using the All of Us Research Program cohort. Methods: We developed a cumulative risk index from nine biological, clinical, and social variables for males with OPC in the United States. Comorbidity burden was measured by the number of unique comorbid diagnoses per patient, excluding HIV/AIDS and primary OPC to reduce circularity. Poisson regression was performed to estimate incidence rate ratios (IRR) for comorbidity by risk group/count. Results: Under strict criteria requiring data for each risk factor, mean comorbidity was 1.90 in the low-risk and 2.29 in the moderate-risk groups; in an inclusive, ‘liberal’ analysis, most cases (74%) were moderate risk with much lower mean comorbidities (mean = 0.050–0.205), with only 5% having any comorbidity recorded. Each additional risk factor was associated with an 81% increase in unique comorbidities (IRR = 1.81, 95% CI: 1.16–2.91; p = 0.01). The high-risk group had substantially higher comorbidity but comprised only two individuals. The most common comorbid diagnoses were essential hypertension and hyperlipidemia, and the most frequent risk factor co-occurrence was having a family history of head and neck cancer and having no insurance. Conclusions: Our analysis demonstrated male OPC patients to have multiple risk factors, but comorbidity burden was concentrated in a small minority, supporting the need for risk stratification and integrated, multidomain prevention and care strategies. Full article

Background: Arterial hypertension is one of the most prevalent chronic non-communicable diseases and a leading cause of cardiovascular morbidity and mortality worldwide. Its burden remains particularly high in rural and resource-limited settings, where access to healthcare is often constrained by shortages of healthcare professionals, geographical barriers, and underdeveloped infrastructure. These factors may contribute to delayed diagnosis, suboptimal disease control, and increased risk of complications. In this context, telemedicine has emerged as a useful approach to supporting hypertension management and improving access to care in rural populations. Methods: This study presents a narrative review of the literature focusing on the application of telemedicine in the management of arterial hypertension in rural populations. A structured literature search of PubMed, Scopus, and Web of Science databases was conducted for studies published between 2015 and 2025. The review included randomized controlled trials, systematic reviews, meta-analyses, and observational studies evaluating telemedicine interventions, including remote blood pressure monitoring, mobile health applications, and teleconsultations. Study selection was guided by relevance to the research objective, with particular attention to rural and resource-limited contexts. Results: Telemedicine interventions have been associated with improvements in blood pressure control, treatment adherence, and access to healthcare services. Evidence from randomized controlled trials and meta-analyses suggests modest reductions in systolic and diastolic blood pressure compared with standard care. However, a substantial proportion of the available evidence originates from studies conducted in general or mixed populations rather than exclusively rural settings. Therefore, the applicability of these findings to rural contexts remains limited and should be interpreted with caution. The effectiveness of telemedicine may vary depending on differences in healthcare infrastructure, resource availability, digital accessibility, and organizational models across healthcare systems. Integrated care approaches involving primary healthcare providers and specialist support may contribute to improved continuity of care, although their impact appears to be context-dependent. Key barriers include limited telecommunication infrastructure, digital literacy challenges, and difficulties in integrating telemedicine into routine clinical practice. Conclusions: Telemedicine may represent a useful approach to supporting hypertension management in rural populations. However, its implementation requires careful consideration of local healthcare systems, patient characteristics, and organizational context. Telemedicine should be viewed as a context-dependent strategy rather than a uniform solution. Further context-specific research is needed to evaluate the long-term clinical, organizational, and economic impact of telemedicine interventions in rural hypertension management. Full article

Dietary sodium excess is a primary driver of hypertension, yet individuals differ markedly in their blood pressure response to salt. This variation, termed salt sensitivity, cannot currently be predicted from clinical variables alone. This review examines three aspects of salt-gut physiology: intestinal sodium handling, salt-induced changes in gut microbiome composition, and microbiota-mediated effects on immune function, metabolite production, and gut barrier integrity. The intestine absorbs dietary sodium through regulated transporters whose activity adapts to luminal and hormonal conditions, making the gut a key regulator of sodium balance. High salt intake consistently alters gut microbiota composition in animal models, most reproducibly depleting Lactobacillus species, with variable effects on overall diversity. These compositional shifts, supported by human data, activate intestinal Th17 cells and deplete short-chain fatty acid producers, contributing to systemic inflammation and elevated blood pressure. The presence of inducible osmoadaptation responses varies substantially across microbes, though activation under dietary sodium conditions has not been demonstrated in vivo. If salt-driven microbial changes contribute causally to hypertension, microbiota-targeted interventions could complement sodium restriction in patients for whom long-term dietary adherence is poor. Controlled sodium intervention studies in animals and humans are needed to establish whether such a causal contribution exists. Full article

Background/Objectives: This study aimed to estimate self-reported prevalence of HIV and gonorrhea among primary healthcare attendees in Riyadh and to identify key demographic, behavioral, and clinical predictors, acknowledging that diagnoses were based on participant self-report rather than laboratory confirmation. Methods: A cross-sectional survey was conducted between March and July 2023 across 48 primary healthcare centers in Riyadh. A total of 14,239 adult participants (aged ≥18 years) completed an electronically administered questionnaire that included self-reported prior diagnoses of HIV and gonorrhea. Multivariable logistic regression models were used to identify independent predictors of self-reported HIV and gonorrhea. Results: The self-reported prevalence of HIV was 2.6% (95% CI: 2.35–2.87%), and gonorrhea was 3.1% (95% CI: 2.83–3.40%). Several factors were independently associated with higher odds of self-reported infection. Younger age (<50 years) increased risk (HIV: AOR = 2.19; gonorrhea: AOR = 1.57), as did female sex (HIV: AOR = 1.67; gonorrhea: AOR = 1.59), higher education (HIV: AOR = 1.29; gonorrhea: AOR = 1.23), married status (HIV: AOR = 1.76; gonorrhea: AOR = 1.49), and insurance coverage (HIV: AOR = 2.01; gonorrhea: AOR = 1.88). Behavioral and clinical factors included smoking (HIV: AOR = 4.79; gonorrhea: AOR = 2.41), hypertension (HIV: AOR = 2.58; gonorrhea: AOR = 1.49), obesity (HIV: AOR = 11.55; gonorrhea: AOR = 9.02), hypercholesterolemia (HIV: AOR = 2.24; gonorrhea: AOR = 2.53), and heart disease (HIV: AOR = 11.31; gonorrhea: AOR = 8.77). The notably high associations for obesity and heart disease should be interpreted with caution, as they may be influenced by detection bias or residual confounding within the healthcare-seeking sample. Conclusions: This study provides key insights into the self-reported burden and predictors of HIV and gonorrhea in Saudi Arabia. While identifying significant demographic and metabolic risk profiles, the high magnitude of certain clinical associations must be interpreted with caution due to potential detection bias and residual confounding. Given the reliance on self-reported data, these findings should be viewed as an epidemiological baseline rather than absolute prevalence. Prioritizing clinical context over statistical values and strengthening integrated, laboratory-based surveillance within primary care will be essential for improving early detection and evidence-based prevention strategies in the region. Full article

Gut microbiome composition influences cardiovascular drug efficacy and safety, yet its integration into heart failure (HF) management remains underexplored. Alterations in intestinal microbial communities have been linked to atherosclerosis, coronary artery disease, heart failure, and hypertension through multiple mechanisms. Dysbiosis disrupts the balance between commensal and pathogenic bacterial species, impairing gut barrier function and activating inflammatory pathways. The altered microbial ecosystem modulates the production of key metabolites—such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acids (BAs)—that directly impact cardiovascular function. This narrative review synthesizes current evidence on bidirectional interaction between heart failure pharmacotherapy and gut microbiome composition. Commonly used drugs in heart failure management show microbiome-dependent pharmacokinetics. Digoxin undergoes bacterial inactivation by Eggerthella lenta, while angiotensin converting enzyme inhibitors and beta-blockers demonstrate enhanced efficacy with specific Firmicutes populations. Conversely, certain probiotic strains attenuate drug-induced gut barrier injury and restore gut homeostasis. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists, and angiotensin receptor–neprilysin inhibitors exhibit beneficial microbiome-modulating effects beyond their primary cardiovascular actions. These findings underscore the potential for microbiome-informed precision medicine in heart failure. However, significant methodological challenges must be addressed, including lack of standardization in microbiome profiling, small sample sizes, and limited longitudinal data. Future research should focus on identifying specific microbial signatures that predict drug response, developing targeted probiotic interventions, and conducting prospective clinical trials to validate pharmacomicrobiomics approaches in heart failure management. Full article

Background/Objectives: Achillea millefolium is a well-known plant used in traditional medicine for the treatment of inflammation, gastrointestinal disorders, respiratory diseases, hypertension, and diabetes, among others. These effects are attributed to the metabolite content of flavonoids and terpenes such as achillin (1) and leucodin (2). Thus, the current investigation aims to standardize the extracts from A. millefollium based on the presence of 1 and 2 and relate them to their relaxant effect in ex vivo assays. Methods: A validated High-Performance Liquid Chromatography (HPLC) method was used to determine the concentration of the main compounds, employing standard molecules previously isolated from the same species and characterized by nuclear magnetic resonance (NMR) and X-ray diffraction. Also, the relaxant effects of both compounds and their combinations were assayed on aortic and tracheal rat rings in an organ bath. Results: Compounds (1) and (2) are the main compounds in hexane, dichloromethane, and hydroalcoholic extracts, present in different proportions. The relaxant effects in ex vivo models of the aorta and trachea showed that the sesquiterpene lactones achillin (1) [Trachea, maximum effect (Emax): 67.67 ± 5.01%, medium effective concentration (EC50): 304.44 ± 2.61 µM; Aorta: Emax: 63.94 ± 6.28%, EC50: 225.73 ± 4.49 µM)] and leucodin (2) (Trachea: Emax: 76.71 ± 4.73%, EC50: 266.40 ± 2.05 µM; Aorta, Emax: 72.96 ± 1.73%, EC50: 163.29 ± 2.99 µM) are responsible for the relaxant effects shown by the extracts. The observed effect is proportional to the concentration of these molecules, with hexane extracts being more active. Additionally, we demonstrate the safety of molecules 1 and 2 through toxicological studies recommended by the OECD. Conclusions: The isolated compounds achillin and leucodin are the primary constituents in the flowers of A. millefolium, with higher concentrations found in hexane extracts, particularly of achillin, which shows a correlation of 2.33 with respect to leucodin. This correlation is closely related to their relaxant effect, as these compounds are the main contributors to the relaxant response in the trachea and aorta, being more effective when used together. Full article

This systematic review was conducted and reported according to the PRISMA 2020 statement to synthesize evidence published between January 2020 and January 2025 on food-derived antihypertensive peptides, with emphasis on mechanisms of action, molecular stability, bioavailability, and functional food applications. PubMed, Scopus, and Web of Science were searched using combined terms related to bioactive or ACE-inhibitory peptides, stability or bioavailability, and alternative protein sources. Original peer-reviewed studies in English evaluating antihypertensive or ACE-inhibitory peptides from plant, marine, insect, fungal, dairy, or terrestrial animal matrices were considered eligible when they reported experimental evidence on activity, stability, transport, or in vivo efficacy. Three reviewers independently screened records and extracted data. A total of 177 studies were included. Plant and marine matrices accounted for approximately 72% of the evidence base, with a strong focus on low-molecular-weight peptides (<3 kDa) and multistage validation pipelines integrating in silico screening, in vitro enzymatic assays, Caco-2 transport models, ex vivo assays, and spontaneously hypertensive rat studies. Overall, the evidence supports the antihypertensive potential of selected food-derived peptides, particularly through ACE inhibition and related vascular mechanisms. Encapsulation and advanced delivery approaches improved peptide stability and bioavailability in several studies. Food-derived antihypertensive peptides represent promising candidates for functional foods and nutraceuticals; however, greater methodological standardization, formal risk-of-bias assessment in primary studies, and well-designed human trials remain necessary to strengthen translation into practice. Full article

Background and Objectives: Whether hyperglycaemia causes hypertension, hypertension worsens glycaemic control, or both conditions arise from shared metabolic drivers remains clinically consequential yet unresolved. This study applies a triangulated causal inference framework to large-scale population data to quantify the direction, magnitude, and robustness of the glucose–blood pressure relationship. The primary objective is to test for bidirectional causal effects between glycaemic status and blood pressure; secondary objectives include quantifying effect magnitudes by multiple complementary methods and assessing robustness to unmeasured confounding. Materials and Methods: We analysed 55,386 adults from the National Health and Nutrition Examination Survey (NHANES, 1999–2023). Multiple causal inference techniques were integrated: directed acyclic graph (DAG) testing, structural equation modelling (SEM) with latent constructs, propensity score matching (PSM), inverse probability weighting (IPW), doubly robust augmented IPW (AIPW), and E-value/Rosenbaum Γ sensitivity analyses, with external replication in the Framingham Heart Study data (n = 4240). Results: All of the methods used confirmed the bidirectional effects. PSM showed that hyperglycaemia increased systolic BP by 1.76 mmHg (95% CI: 0.58–2.96, p = 0.005), and hypertension increased fasting glucose by 6.55 mg/dL (95% CI: 4.61–8.58, p < 0.001), revealing a marked asymmetry favouring the BP → glucose direction. AIPW confirmed both effects (3.51 mmHg and 6.15 mg/dL, both p < 0.001). SEM identified significant bidirectional structural paths between latent glycaemic and blood-pressure constructs, with the Glycaemic → BPState path showing a negative coefficient (β = −0.15, p = 0.043), a sign reversal attributable to conditioning on the shared latent metabolic-syndrome factor. Sensitivity analyses indicated that an unmeasured confounder would need associations of RR ≥ 1.40–1.64 with both exposure and outcome to nullify these estimates, representing moderate robustness. Conclusions: The BP → glucose pathway is the dominant causal direction, suggesting that prioritisation of hypertension control may yield underappreciated benefits for glycaemic regulation. These findings support integrated cardiometabolic management strategies. Full article

Background/Objectives: Familial hyperaldosteronism type IV (FH-IV) is an extremely rare, clinically heterogeneous condition representing the least characterized familial subtype of primary aldosteronism (PA) caused by germline gain-of-function CACNA1H mutations. Despite growing molecular insights, optimal diagnostic and therapeutic strategies remain poorly defined. This systematic review aims to synthesize available evidence regarding the clinical, biochemical, and genetic characteristics of FH-IV, and to evaluate the efficacy of current pharmacological and surgical treatments. Methods: A systematic review was conducted in accordance with PRISMA guidelines and preregistered in PROSPERO (CRD420261324945). A comprehensive search of MEDLINE, Embase, and Web of Science identified studies reporting genetically confirmed FH-IV patients. Data concerning clinical phenotypes, diagnostic evaluations, treatment outcomes, and genetic backgrounds were extracted and analyzed. Results: The primary cohort included 31 fully characterized symptomatic patients, alongside 8 mutation-positive relatives (4 asymptomatic carriers and 4 symptomatic individuals). The genetic landscape was remarkably heterogeneous, encompassing 17 distinct CACNA1H mutations. Clinically, diagnosis was frequently delayed, often complicated by atypical normokalaemic presentations and misleading adrenal imaging. Surgical treatment was generally ineffective, frequently resulting in persistent or recurrent hypertension and biochemical dysregulation. Pharmacologically, patients often required multiple antihypertensive drugs, most frequently a combination of mineralocorticoid receptor antagonists (MRAs) and calcium channel blockers (CCBs). Conclusions: FH-IV is best conceptualized as a systemic adrenal channelopathy. While standard screening parameters are usually elevated, atypical biochemical profiles and misleading structural imaging can complicate the diagnostic process. Optimal management relies on multigene Next-Generation Sequencing (NGS) panels for definitive diagnosis and cascade screening of relatives. Finally, while the combination of MRAs and CCBs is commonly used in PA, it represents a valuable therapy for FH-IV, with dual L-/T-type CCBs emerging as a potential disease-specific option. Full article

Background: Sedation-related adverse events remain a concern during endoscopic retrograde cholangiopancreatography (ERCP), even when sedation is administered by anesthesiologists. Standard monitoring may not accurately reflect sedation depth. Electroencephalogram-based monitoring using Entropy provides an objective assessment of sedation depth and may optimize sedation management. Methods: This prospective, single-center, observational cohort study included 100 adult patients undergoing ERCP under anesthesiologist-administered sedation. Patients were allocated to two study groups: standard monitoring or advanced monitoring. The primary outcome was the incidence of sedation-related adverse events. Secondary outcomes included sedation depth, hemodynamic parameters, and recovery profiles assessed by the Aldrete score. Results: The overall incidence of sedation-related adverse events did not differ significantly between groups. However, the Entropy-monitored group had a significantly lower incidence of hypertensive episodes (6% vs. 26%, p = 0.007) and showed a trend toward fewer cardiopulmonary events. Sedation depth correlated significantly with adverse events, with deeper sedation associated with increased hemodynamic instability. Despite achieving slightly deeper sedation, patients in the Entropy group demonstrated significantly faster recovery, with higher Aldrete scores at 5 min (p = 0.003) and 15 min (p < 0.001). Conclusions: Entropy monitoring during anesthesiologist-administered sedation for ERCP was not associated with a significant reduction in overall adverse event incidence, a finding that should be interpreted in the context of the study’s limited statistical power (29.3%). However, it was associated with a significantly lower incidence of intraprocedural hypertension and faster postprocedural recovery, suggesting a role in optimizing sedation depth and hemodynamic stability rather than broadly reducing composite adverse events. These findings are hypothesis-generating and require confirmation in larger, adequately powered randomized controlled trials before clinical implementation can be recommended. Full article

Background. Despite technological innovations and improvements in stents and devices, sex-related discrepancies are still reported in the outcomes after ST-segment elevation myocardial infarction (STEMI), depending on biological and sex-specific pathophysiological differences, which have not been completely understood. The aim of the present study was to provide real-world data on the prognostic role of sex among patients with STEMI, enclosed into a recent up-to-date international registry. Methods. The ISACS-STEMI COVID-19 is a large-scale retrospective registry, including STEMI patients treated with mechanical reperfusion between 1 March and 30 June, 2019 and 2020. Patients, treated in 109 centers across Europe, Latin America, Southeast Asia, and North Africa, were grouped according to sex. Primary endpoint: In-hospital mortality; secondary endpoints: Time delay, 30-day mortality, and postprocedural Thrombolysis In Myocardial Infarction (TIMI) 3 flow. Results. We included 16,083 patients, 24.3% females (54.3% hospitalized in 2019, 45.7% in 2020). Women with STEMI were older, more often diabetic and hypertensive (p < 0.001), with a higher prevalence of hypercholesterolemia (p = 0.02), longer ischemia time (p = 0.01), ambulance referral (p = 0.03) and cardiogenic shock at presentation (p = 0.05), but less frequently smokers, with a previous cardiovascular event (p < 0.001) or anterior STEMI (p = 0.03) as compared to males. Preprocedural TIMI 0 flow, multivessel disease, need for thrombectomy (p < 0.001 and p = 0.001, respectively), use of Glycoprotein IIbIIIa inhibitors or cangrelor, radial access and implantation of drug-eluting stents (p < 0.001, p < 0.001 and p = 0.001, respectively) were also more common in men. Impaired postprocedural epicardial reperfusion (TIMI flow 0–2) was observed more frequently in females as compared to males (10% vs. 7.2%; adjusted OR [95% CI] = 1.30 [1.13–1.49], p = 0.01). In-hospital mortality was 5.8%, significantly higher among women (8.3% vs. 5%, p < 0.001, adjusted HR [95% CI] = 1.26 [1.06–1.5], p = 0.01). Similar data were observed for 30-day mortality (10.3% vs. 6.2%, p < 0.001, adjusted HR [95% CI] = 1.22 [1.06–1.38], p = 0.007). Conclusions. Among STEMI patients being treated with the most updated standard of care for primary percutaneous coronary intervention, female sex is still associated with higher complexity and impaired prognosis, displaying suboptimal epicardial reperfusion and increased in-hospital and 30-day mortality. Full article

Background/Objectives: Placental abruption remains one of the leading causes of maternal morbidity, and the development of disseminated intravascular coagulation (DIC) significantly worsens outcomes. We sought to develop and internally validate a prediction model—the Placental Abruption DIC (PAD) Score—using parameters routinely collected at presentation. Methods: We conducted a retrospective cohort study at a tertiary referral center in Istanbul, Turkey (January 2019–December 2024). Women with singleton pregnancies ≥22 weeks diagnosed with placental abruption were eligible. The primary outcome was overt disseminated intravascular coagulation (DIC) within 24 h of admission, adjudicated using the original International Society on Thrombosis and Haemostasis (ISTH) overt DIC scoring algorithm; a total score of ≥5 was considered compatible with overt DIC. We built a multivariable logistic regression model with bootstrap internal validation (1000 resamples). Robustness was evaluated through prespecified sensitivity analyses including complete-case analysis, single imputation, Firth-penalized logistic regression, exclusion of patients transferred from external facilities, a four-variable model excluding preeclampsia, and alternative score threshold grouping. Comparative discrimination against the admission ISTH overt DIC score, the Erez pregnancy-modified DIC score, and the Kobayashi obstetrical DIC score were evaluated using the area under the receiver operating characteristic curve and DeLong testing. Results: Of 237 women, 54 (22.8%) developed DIC. The final model retained five predictors: fibrinogen concentration, shock index, platelet count, placental separation percentage, and chronic hypertension/preeclampsia. The optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.916, with calibration slope 0.96 and Brier score 0.12. DIC incidence was 2.9% in low-risk (0–4 points), 7.6% in moderate-risk (5–8 points), and 86.0% in high-risk (≥9 points) patients. Discrimination remained stable across complete-case (AUC 0.909), single-imputation (0.913), Firth-penalized (0.914), transfer-excluded (0.902), four-variable (0.892), reduced three-predictor (0.842, excluding fibrinogen and platelet count), pathology-confirmed subgroups (0.887) and composite clinical outcome (0.801) analyses, and exceeded that of the ISTH (0.812), Erez (0.848) and Kobayashi (0.793) comparator scores. Conclusions: The PAD Score offers a straightforward method for stratifying DIC risk in placental abruption. External validation in independent cohorts is needed before clinical implementation. Full article

Background: Cyclosporine A (CsA) is a cornerstone in graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT), and a higher starting dose of 5 vs. 3 mg/kg reduces the risk of acute GVHD. Since hypertension is a relevant side effect of CsA, data on whether a higher CsA starting dose affects the incidence of hypertension are warranted. Methods: In this monocentric cohort study, 367 patients with no preexisting hypertension and treated with a CsA-containing GVHD prophylaxis were included: 230 (63%) with a CsA starting dose of 3 mg/kg and 137 (37%) with 5 mg/kg. The primary outcome was the incidence of early new-onset hypertension during the engraftment period. Potential risk factors for early new-onset hypertension were assessed using uni- and multivariable Cox regression models. Results: Overall, the cumulative incidence of early new-onset hypertension was 67% (246/367), but the incidence rate for early new-onset hypertension in the higher CsA group was lower (CsA 5 vs. 3 mg/kg: 57 vs. 67 per 1,000 patient-days; p = 0.414). In the multivariable analysis, risk factors for early new-onset hypertension were advanced patient age, obesity and prior autologous HCT, while a higher CsA starting dose was not associated with increased early new-onset hypertension (adjusted hazard ratio, 0.90; 95% CI, 0.67–1.21). Conclusions: A higher CSA starting dose of 5 vs. 3 mg/kg did not increase the risk of hypertension. Since previous analyses demonstrated a reduction in GVHD with a higher CsA starting dose of 5 mg/kg, current findings further support the safety of a higher CsA starting dose. Full article