In severe acute kidney injury (AKI), delayed renal replacement therapy (RRT) strategies allow many KDIGO stage-3 patients to avoid dialysis, but excessive postponement in those who ultimately require RRT may worsen outcomes. Early physiologically grounded markers to identify patients likely to need RRT are lacking. We evaluated whether combining early glomerular filtration kinetics and timed urinary urea excretion could improve discrimination of subsequent RRT initiation under a delayed strategy.

TUBSAKI is a prospective bicentric ICU cohort including adults with KDIGO stage-3 AKI managed with a protocolized delayed RRT strategy. Blood and 24-hour urine samples were collected at diagnosis (D0) and day 1 (D1). Glomerular filtration dynamics were assessed using kinetic GFR (kGFR), and timed urinary urea excretion was assessed using UUEI. Discrimination for subsequent RRT was assessed using ROC curves and AUC. A combined logistic model (kGFR D0-D1 + UUEI D1) was internally validated by bootstrap, with sensitivity analyses adjusted for SOFA and KDIGO stage-3 oliguria.

Among 110 patients, 31 (28%) required RRT. kGFR D0-D1 showed good discrimination (AUC 0.81 [0.72-0.89]), and UUEI D1 moderate discrimination (AUC 0.74 [0.63-0.82]). The combined model showed an AUC of 0.85 ([0.76-0.91]), optimism-corrected AUC 0.83, and acceptable calibration. Discrimination remained stable after adjustment for SOFA and oliguria. Incremental gain over kGFR alone was modest and not statistically significant.

Early glomerular filtration kinetics and urinary urea excretion were associated with subsequent RRT initiation under a delayed strategy. The incremental clinical value of UUEI remained limited in this cohort, and external validation is required before clinical use.

Prader-Willi syndrome (PWS) is a rare imprinting disorder characterized by typical dysmorphic features, lack of satiety, infantile hypotonia, and later morbid obesity with complications, short stature, hypogonadotropic hypogonadism, skeletal and psychiatric problems. From the literature, it is well known that patients with PWS have a more favorable metabolic pattern than healthy controls.

The aim of the study is to assess the metabolic profile of PWS patients followed at an Expert Center for Rare Endocrine Diseases compared with healthy controls and to look for relations between components of the metabolic syndrome (MetS), adipokines, and the compartments of body composition (BC-lean and fat mass).

The current study is a cross-sectional evaluation of 25 patients with Prader-Willi syndrome (mean age 11.3 ± 8.2 years), with a total of 183.6 patient-years of regular follow-up (from the first visit to the center to the data collection cutoff date), compared with 24 age-, sex-, and BMI-matched healthy controls (mean age 11.3 ± 3.9 years). Each participant underwent anthropometric measurements, physical examination, biochemical and hormonal blood sampling, and whole-body DXA scan. Statistical analysis (SPSS 15.0 statistical package, Chicago, IL, USA) was performed to assess the relations between the metrics in the PWS group compared with controls.

Patients with PWS showed a better profile of glucose homeostasis with significantly lower serum insulin concentration and calculated HOMA-IR index compared with the controls (p < 0.05). Taking into consideration age, sex, and body mass index (BMI) in the PWS group, the analysis showed strong positive correlations between waist circumference (WC) and systolic blood pressure (SBP) (r = 0.864, p < 0.001), and WC and diastolic blood pressure (DBP) (r = 0.534, p = 0.033). Partial correlation analysis with respect to age, sex, and pubertal development found significant positive WC correlations with insulin (r = 0.796, p = 0.006), HOMA-IR (r = 0.697, p = 0.025), LDL-cholesterol (r = 0.735, p = 0.002), uric acid (r = 0.735, p = 0.002), CRP (r = 0.600, p = 0.023), and leptin (r = 0.730, p = 0.005). Strong negative correlations existed between WC and SHBG (r = -0.772, p = 0.002) and HMW adiponectin (r = -0.998, p = 0.044). Additionally, a negative correlation of HMW adiponectin and SBP was demonstrated. 88% of the patients were treated with recombinant human growth hormone (rhGH). Bone mineral density adjusted for height (BMD/height) was significantly lower in patients with PWS (p < 0.05) compared with healthy controls. The analysis did not reveal significant relationships between BC compartments and metabolic and auxological parameters in the PWS group.

Our study confirms that patients with PWS have a favorable metabolic profile compared with healthy controls matched by age, sex, and BMI. Syndromic participants who manifest greater accumulation of abdominal adipose tissue have a higher risk of hemodynamic changes and metabolic disturbances predictive of the development of cardiovascular diseases (CVD) in adulthood. WC could serve as a predictive marker for detecting higher metabolic risk in this syndromic group of patients, and both WC and HMW adiponectin for hypertension. In the future, on this basis, we could possibly implement both of these metrics in clinical practice.

Tubulointerstitial fibrosis (TIF) is a key pathological hallmark and a major determinant of end-stage renal disease (ESRD). The mechanisms of TIF remain unclear, and there are currently no specific drugs to slow or reverse its progression. Notably, due to the kidney's unique structure, the course of renal dysfunction is intimately connected with hypoxia. The signaling pathway formed by hypoxia-inducible factor 1α (HIF-1α) and its downstream target gene, B-cell lymphoma-2/adenovirus E1B 19-kDa interacting protein (BNIP3), exerts a pivotal effect during renal hypoxia. This pathway mediates mitophagy, inhibits apoptosis and inflammatory responses, maintains cellular energy balance, and thus profoundly influences the progression of TIF. This article focuses on the molecular mechanism by which the HIF-1α/BNIP3 pathway regulates mitophagy and affects TIF, and delves into its mechanisms in pyroptosis, oxidative stress, and ischemia-reperfusion injury, This work endeavors to establish a theoretical foundation and potential intervention targets for developing novel treatment strategies for TIF.

The human vascular network is a highly dynamic, complex and organ-specific microenvironment essential for organ homeostasis. Traditional 2D cell cultures fail to capture its complex intercellular interactions, tissue-specific architectures, and mechanobiological cues. Blood vessel organoids (BVOs) generated from human induced pluripotent stem cells (hiPSCs) replicate the structure and function of blood vessels. Because hiPSCs preserve the donor's telomere length and epigenetic memory, BVOs may preserve the genesis memory, opening up a completely new avenue for the study of vascular disorders. In this review, we systematically outline the methods for in vitro blood vessel generation and explore how vascularizing parenchymal organoids actively drives tissue maturation while overcoming hypoxic limitations. We assess the vital transition from biochemical induction to biomechanical integration, highlighting how microfluidic organ-on-a-chip (OoC) platforms resolve the lineage-specific media dilemma and impose the physiological shear stress necessary for definitive vascular maturation. Furthermore, we comprehensively summarize the applications of BVOs as personalized preclinical avatars across diverse pathologies, including diabetic vasculopathy, cerebrovascular and cardiovascular diseases, tumor immune evasion, hereditary anomalies, and infectious vasculotropism. Finally, we address critical current bioengineering constraints-notably incomplete vessel maturation, the absence of functional lymphatic systems, and the lack of immunocompetent microenvironments-providing strategic future perspectives to accelerate the translation of BVOs in precision and regenerative medicine.

The American Heart Association's PREVENT equations estimate risk of total cardiovascular disease (CVD), atherosclerotic CVD (ASCVD), and heart failure (HF) to guide lipid and blood pressure-lowering therapy in people ages 30 to 79 years in the United States. The SCORE2 risk algorithm is used to estimate CVD risk for similar purposes in people ages 40 and older in Europe. Neither set of equations has been comprehensively validated in global observational cohorts and randomized trials. Here, in 44 observational cohorts and 18 randomized trials, we assessed discrimination and calibration of the two risk algorithms across geographical regions (North America, Europe, Asia/other, multi-region trials). We also created scaling factors for risk prediction over 1-9 years using the PREVENT equations, enabling shorter-term risk prediction for research purposes or to facilitate clinical trial enrolment. Over 5.1 years of mean follow-up, 293,737 PREVENT total CVD events (fatal and non-fatal ASCVD or HF) and 258,086 SCORE2 CVD events (myocardial infarction, stroke, or cardiovascular death) were observed among 6,422,714 and 5,437,384 individuals, respectively. Despite differences in CVD outcome definitions, target populations and predictor variables, overall discrimination and calibration were similar for both equations, with generally good performance across regions, including in multi-regional randomized trials. These findings lend support for adoption of PREVENT or SCORE2 for cardiovascular risk stratification across diverse settings.

Sex and gender shape disease presentation, diagnostic accuracy, treatment response and clinical outcomes in rheumatology, yet these dimensions remain insufficiently embedded in clinical practice. Owing to the markedly unbalanced sex prevalence ratios across many rheumatic diseases, the 'minority' sex is consistently under-represented in clinical studies, limiting the interpretation of long-term outcomes and treatment effectiveness. Sex-related differences in pain perception, inflammatory biomarkers and imaging patterns further complicate disease assessment, and treatment allocation and drug persistence also differ between women and men. Gender-related factors - including disparities in care-seeking behaviours, social roles and lifestyle factors - additionally modulate symptom burden and disease trajectories. Evidence remains particularly scarce for transgender, gender-diverse and intersex individuals, who are rarely captured in clinical cohorts, restricting the development of inclusive and generalizable evidence. Embedding sex-aware and gender-aware approaches into diagnostic reasoning, risk assessment and therapeutic decision-making is therefore essential for advancing precision, equity and truly personalized rheumatological care. Such integration enables clinicians to interpret disease signals more accurately, anticipate divergent multimorbidity trajectories and tailor treatment strategies to the biological and sociocultural contexts of each patient.

Individuals with obesity are at higher risk for premature mortality compared to the general population. However, whether achieving multiple modifiable risk factors within target ranges is associated with attenuated excess mortality risk in obesity remains unclear. We included 83,505 participants with obesity and 143,198 individuals without obesity from the UK Biobank, all free of baseline cancer and cardiovascular disease (CVD). The main exposure was the number of risk factors within target range, including glycated hemoglobin < 48 mmol/mol, low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L, absence of albuminuria, non-current smoker, and systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg. Cox proportional hazards models adjusted for age, sex, ethnicity, education, socioeconomic status, alcohol intake, healthy diet score, and physical activity were used to evaluate the association between the degree of risk factor within target range and risks of all-cause, cancer, CVD, and other-cause premature mortality. Fine-Gray competing risk models were performed as sensitivity analyses. The proportional hazards assumption was verified using Schoenfeld residuals. Among individuals with obesity, each additional risk factor within target range was associated with 17%, 11%, 28%, and 16% lower risks of all-cause, cancer, CVD, and other-cause premature mortality, respectively. Participants with obesity who achieved all five risk factors had 47%, 38%, 63%, and 47% lower risks compared to those meeting ≤ 2 factors. However, as the number of risk factors within target range increased, the excess mortality risks progressively diminished. Individuals with obesity meeting all 5 factors showed risks approaching those of individuals without obesity, particularly for CVD and other-cause mortality. Achieving multiple modifiable risk factors within target ranges was associated with substantially lower premature mortality risk among individuals with obesity.

Polygenic scores can improve atrial fibrillation risk prediction. However, limited accuracy and cross-ancestry transferability hinder clinical translation. Here, we explore several ensemble approaches to generate ancestry-optimized polygenic scores, with development in diverse participants from the All of Us Research Program, BioBank Japan, and three additional cohorts. Our ancestry-specific multi-trait approach particularly improves prediction in South-Asian (odds-ratio/standard deviation 1.5-1.8; area under curve 0.60-0.64; relative R² +71%), Admixed-American (1.5; 0.60; +34%) and African ancestry groups (1.4; 0.57; +56%). Nevertheless, performance remains highest in European and East-Asian ancestries (1.8-2.2; 0.65-0.68), where >50% of SNP-heritability is explained. Improved risk stratification is also observed at the extremes, identifying European and East-Asian ancestry individuals with risk comparable to rare TTN variants (e.g., 6-11% with >4-fold odds). Finally, our scores improve incident risk prediction alongside clinical models. Together, we show that our ancestry-tailored multi-trait polygenic scores advance atrial fibrillation risk prediction and stratification, providing an equitable foundation for implementation.

Hypertension (HTN) is one of the most prevalent cardiovascular comorbidities in patients with obstructive sleep apnoea (OSA). Although OSA severity measured by the apnoea-hypopnoea index (AHI) is a known risk factor, the role of hypoxic load in HTN remains less well established.

We analysed data from 12,141 patients with OSA enrolled in the European Sleep Apnea Database (ESADA). Clinical and sleep study parameters were assessed to identify factors associated with HTN.

The cohort included 2650 patients with mild OSA, 3339 with moderate OSA, and 6152 with severe OSA. The mean age was 53.1 ± 12.5 years, the mean body mass index (BMI) 31.7 ± 6.2 kg/m², and 73.1% were male. HTN was present in 41.8% of the patients. In univariate analyses, older age, female sex, obesity, larger neck circumference, greater OSA severity as measured by AHI or oxygen desaturation index (ODI), minimum oxygen saturation (SpO₂), and increased hypoxic load (T90% ≥ 5%) were significantly associated with HTN. After adjustment for age, sex and BMI, increased neck circumference, higher AHI and T90% ≥ 5% remained independently associated with HTN. Notably, HTN prevalence was higher in mild-to-moderate OSA patients with T90% ≥ 5 than in severe OSA patients with T90% < 5 (51.5% vs. 42.8%, p < 0.001). Following propensity score matching, only minimum SpO₂ (p = 0.022) and T90% ≥ 5% (p = 0.044) remained significantly associated with HTN.

Hypoxic load as reflected by T90% and minimum SpO₂, rather than AHI alone, is independently associated with hypertension in patients with OSA, underscoring the importance of oxygenation metrics in cardiovascular risk assessment.

Varicocele is a common cause of male infertility, often associated with impaired sperm quality, hormonal imbalance, and increased DNA fragmentation. Electroacupuncture (EA) has been proposed as an adjunct therapy to improve reproductive parameters, but clinical evidence remains limited.

This case report describes a 38-year-old male with a varicocele treated at Dr. Moewardi General Hospital, Indonesia. The patient underwent 16 sessions of EA therapy. Sperm parameters and serum testosterone levels were measured before and after treatment. Following EA, sperm concentration improved from 5.2 to 6.7 × 106/mL, motility increased from 43% to 60%, and normal morphology rose from 1% to 3%. Testosterone levels increased from 329.6 to 596.2 ng/dL, while the DNA Fragmentation Index (DFI) decreased from 40% to 19.6%.

This case suggests that EA therapy may improve sperm quality, enhance testosterone levels, and reduce DFI in a patient with varicocele. However, further controlled studies are needed to confirm these findings due to the limitations of a single case report.