Limited data are available on pancreatic arteriovenous malformations (AVMs) in patients with hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease. This systematic review aimed to identify all reported cases of pancreatic AVMs in patients with HHT and summarise patient demographics, clinical presentation, diagnostic modalities, treatment strategies and follow-up.

Systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Databases PubMed, Embase, Cochrane Library and Web of Science were systematically screened up to June 2025.

All English-language, full-text studies reporting pancreatic AVMs in patients with HHT. Only patients with definite diagnoses of HHT and pancreatic AVM were included.

All identified articles were independently screened by two reviewers. Data regarding patient demographics, clinical presentation, diagnostic modalities, treatment strategies and follow-up were collected. The mean AVM size was calculated when individual AVM size and number of AVMs were reported.

Of 429 screened records, 46 articles underwent full-text assessment. Nineteen patients from 13 studies met the inclusion criteria. Most patients were female (58%), with a mean age of 52 years, presenting asymptomatically (50%) without laboratory findings (73%). CT was the most frequently used diagnostic modality (56%), and the mean AVM size was 7.1 mm. Most patients were treated conservatively (69%). Prognosis was frequently unavailable (79%). Differential diagnoses consisted mostly of neuroendocrine tumours (75%).

Pancreatic AVMs in patients with HHT appear to be smaller and are more frequently asymptomatic compared with the general population. Severe complications, such as portal hypertension and gastrointestinal bleeding, were less frequent. Conservative management was most common. Additional studies are needed to better characterise prognosis and treatment outcomes, particularly in symptomatic patients.

CRD420251077109.

Acute kidney injury (AKI) is one of the most common and consequential complications after cardiac surgery. Despite improvements in perioperative care, no pharmacological intervention has been definitively shown to prevent AKI following cardiac surgery. Recombinant human brain natriuretic peptide (rhBNP) shares structural and biological activity with endogenous brain natriuretic peptide and has demonstrated favorable natriuretic, diuretic, and renal hemodynamic effects in prior studies. However, robust randomized evidence on whether perioperative rhBNP can prevent AKI is lacking.

This is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group trial comparing perioperative rhBNP with placebo in high-risk patients undergoing elective on-pump cardiac surgery. A total of 694 participants will be randomized 1:1 to receive a continuous intravenous infusion of rhBNP (0.01 µg/kg/min) or matched normal-saline placebo, initiated between anesthesia induction and the onset of cardiopulmonary bypass and continued for 48 ± 2 hours. The primary efficacy endpoint is the incidence of AKI within 7 postoperative days defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints include AKI severity and duration, renal replacement therapy during the index hospitalization, major adverse kidney events at 30 and 90 days (MAKE-30, MAKE-90), 30-day all-cause mortality, intensive care unit and total length of stay.

To our knowledge, PROTECT-CS is the first adequately powered, multicenter, double-blind randomized trial designed to evaluate whether perioperative rhBNP prevents AKI after high-risk cardiac surgery. The study is intended to provide high-quality evidence to inform clinical practice and future guideline recommendations on pharmacological renal protection in cardiac surgery patients.

ClinicalTrials.gov, identifier NCT07617675.

Currently available clinical tools have shown very limited ability to predict bleeding risk during oral anticoagulant (OAC) therapy. Polygenic risk scores (PRSs) have shown promise for improving risk prediction in cardiovascular diseases, but their clinical utility for predicting bleeding risk remains unknown. We evaluated whether PRSs for intracranial hemorrhage and gastrointestinal bleeding improve bleeding risk prediction in patients receiving OAC therapy.

We conducted a registry-based cohort study using genotype and linked health registry data from the FinnGen study. The study included 83,186 individuals receiving OAC therapy. PRSs for intracranial hemorrhage and gastrointestinal bleeding were constructed using the novel SBayesRC method and evaluated as continuous and categorical variables in Cox proportional hazards models. Predictive performance was assessed using Harrell's C-index and compared with the HAS-BLED score.

During follow-up, 970 intracranial hemorrhages and 2074 gastrointestinal bleeding events occurred. Continuous PRSs were not associated with intracranial hemorrhage (adjusted hazard ratio [HR] per SD, 1.06; 95% CI, 0.99-1.13) or gastrointestinal bleeding (adjusted HR, 1.04; 95% CI, 0.99-1.09). Individuals in the lowest PRS category had a lower risk of gastrointestinal bleeding (adjusted HR, 0.67; 95% CI, 0.47-0.96), but this finding was not replicated using alternative PRS methods or GWAS data. Adding PRSs to the HAS-BLED score did not improve discrimination for intracranial hemorrhage (C-index, 0.62 vs. 0.62) or gastrointestinal bleeding (0.60 vs. 0.60).

Bleeding PRSs provide no meaningful improvement in bleeding risk prediction among patients receiving OAC therapy and do not enhance risk stratification beyond established clinical risk factors.

Primary percutaneous coronary intervention restores epicardial flow after ST-segment elevation myocardial infarction, but tissue perfusion may remain impaired. Coronary microvascular dysfunction, angiographic no-reflow, cardiac magnetic resonance-defined microvascular obstruction, and intramyocardial hemorrhage are overlapping but non-equivalent phenotypes. This review examines reduced mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity as a susceptibility amplifier rather than an established independent cause of these outcomes. Reperfusion generates reactive oxygen species that initiate lipid peroxidation and produce electrophilic aldehydes, including 4-hydroxy-2-nonenal, malondialdehyde, and acrolein. Their effects are shaped by compartmental generation, competing clearance systems, protein-adduct persistence, and positive feedback between mitochondrial injury and inflammation. Methylglyoxal is considered a parallel, glyoxalase-dominant dicarbonyl pathway rather than a principal ALDH2 substrate. The resulting network may impair endothelial nitric oxide signaling and barrier integrity, promote platelet activation and neutrophil extracellular trap formation, and increase cardiomyocyte edema and damage-associated molecular-pattern release. Pericyte constriction contributes to experimental no-reflow, whereas pericyte sensitivity to 4-hydroxy-2-nonenal remains a theoretical hypothesis awaiting direct experimental confirmation. We also assess adductomics, proteomics, lipidomics, and time-resolved sampling strategies. Free aldehydes are chemically and preanalytically unstable; protein-bound adducts provide longer detection windows but lack the clinical standardization of cardiac troponin. ALDH2 activation remains preclinical for reperfusion microvascular injury. Prospective studies should further integrate genotype, enzyme activity, local carbonyl measurements, thromboinflammatory phenotyping, invasive physiology, and cardiac magnetic resonance endpoints.

In Fontan circulation, pulmonary blood flow depends on low atrial pressure and preserved atrioventricular (AV) synchrony. AV dyssynchrony as a driver of Fontan failure and Fontan-associated liver disease remains under-recognized.

A 17-year-old boy with Fontan failure, Fontan-associated liver disease, portal hypertension, and effusions had elevated Fontan pressures despite subaortic obstruction relief and Fontan tunnel stenting. Invasive pressure tracings identified junctional rhythm with AV dyssynchrony. Epicardial atrial pacing, preserving AV conduction and avoiding ventricular pacing, normalized Fontan pressures with clinical improvement and a reduction in liver stiffness.

In patients with failing Fontan circulation and junctional rhythm, restoring AV synchrony by atrial pacing may reverse Fontan hypertension and improve end-organ congestion.

Junctional rhythm should be considered a reversible contributor to elevated Fontan pressures before attributing failure to anatomy. Atrial pacing, when AV conduction is intact, can improve Fontan hemodynamics and hepatic congestion while avoiding ventricular pacing.

Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion disorder characterized by progressive external ophthalmoplegia, pigmentary retinopathy, and cardiac conduction abnormalities. Dental management may be complicated by developmental enamel defects, high caries burden, limited cooperation, and anesthetic considerations related to multisystem mitochondrial disease. Published dental case reports focused specifically on pediatric KSS remain extremely sparse.

We describe the staged dental management of a 10-year-old girl with genetically confirmed KSS and ASA III systemic status. Clinical and radiographic assessment revealed multiple active cavitated carious lesions, localized demarcated enamel hypomineralization, plaque-induced gingivitis, chronic apical and furcation inflammatory lesions associated with teeth 47 and 46, and early apical inflammatory changes at tooth 37. Notably, the radiographic extent of posterior mandibular pathology exceeded the severity of the overlying soft-tissue findings. Treatment was organized in stages and included extraction of non-restorable teeth (37, 46, 47, 55, and 65) under elective endotracheal general anesthesia in a licensed day-care dental facility, followed by restorative treatment of the remaining teeth under local anesthesia during short, structured outpatient visits using pragmatic, time-efficient techniques and intensive caregiver-supported prevention.

This case shows that comprehensive dental care in a child with KSS is feasible when treatment is staged, interdisciplinary, and explicitly adapted to medical vulnerability and limited cooperation. In such patients, radiographically significant apical pathology may be present despite only modest clinical soft-tissue signs. Because chronic apical periodontitis can progress silently in any child with irregular dental attendance, the principal practical lesson is the importance of timely radiographic assessment when deep caries or pulpal involvement is suspected, particularly in medically complex children.

Most research on sea buckthorn (Hippophae rhamnoides L.) has focused on the berries and oils. This structured narrative review examines the chemical profile of the leaves and evaluates cardiovascular and metabolic evidence from leaf preparations, isolated constituents, and other sea buckthorn materials. Two complementary PubMed searches yielded 3539 unique records. After screening in successive stages, 85 publications were included. A supplementary search in Scopus yielded no unique records. Leaves contain glycosides of isorhamnetin, quercetin, and kaempferol, together with ellagitannins, proanthocyanidins, phenolic acids, and triterpenoids. Their relative amounts vary between cultivars, harvest, processing, extraction, and the denominator used for reporting. Leaf preparations improved selected metabolic, vascular, or inflammatory outcomes in several animal and ex vivo models. Studies of isolated flavonols support biological plausibility but do not identify the compounds responsible for effects of complete leaf preparation. Human trials have examined berries, purée, juice and oils; effects on lipids, glucose regulation, blood pressure, and platelet activity were generally small or inconsistent. No controlled human trial or human pharmacokinetic study has evaluated a chemically characterized leaf preparation. This absence is the main obstacle to clinical translation. The next stage should compare one defined leaf preparation with appropriate controls in validated animal models, test fractions prepared from the same leaf batch, and require replication before human studies of pharmacokinetics, dose, safety, and efficacy. Current evidence supports this sequence but does not justify therapeutic use of sea buckthorn leaves.

Background and Objectives: Stroke, a neurological disorder caused by damage to the central nervous system, is commonly accompanied by impairments in motor and sensory function and muscle strength. We compared the effects of progressive squat exercises performed under varying support-surface stability conditions on quadriceps femoris muscle thickness in patients 6 months to less than 1 year after stroke, using rehabilitative ultrasound imaging. Materials and Methods: This randomized, open-label, parallel-group controlled trial assessed 36 patients with stroke for eligibility. Four individuals were excluded before randomization; the remaining 32 participants were randomly assigned in a 1:1 ratio to either the unstable-support-surface squat exercise group (n = 16) or the stable-support-surface squat exercise group (n = 16). Both groups performed progressive squat exercises five times per week for 4 weeks. Quadriceps femoris muscle thickness was measured before and after the intervention using rehabilitative ultrasound imaging. Results: Between-group comparisons of changes from baseline showed significantly greater increases in rectus femoris and vastus medialis muscle thickness in the unstable support-surface squat exercise group than in the stable support-surface squat exercise group (p < 0.05). No significant between-group differences were observed in vastus intermedius or vastus lateralis muscle thickness (p > 0.05). Conclusions: Progressive squat exercise performed on an unstable support surface resulted in greater increases in rectus femoris and vastus medialis muscle thickness than the same exercise performed on a stable support surface. However, these findings are limited to muscle thickness and should not be interpreted as evidence of improved muscle strength or functional performance.

Patent ductus arteriosus (PDA) is a common congenital heart disease (CHD) with a complex genetic basis. The transcription factor MEF2C plays a critical role in cardiac development, but the role of promoter region variants in PDA has not been explored. This study aimed to identify MEF2C promoter variants in PDA patients and investigate their functional consequences. We sequenced the MEF2C promoter region in 318 children with PDA and 306 healthy controls. Identified variants were subjected to dual-luciferase reporter assays in A7r5 vascular smooth muscle cells to assess transcriptional activity. Bioinformatics (JASPAR) and electrophoretic mobility shift assays (EMSA) were used to predict and validate changes in transcription factor binding. Seventeen variants were identified, of which seven were present exclusively in PDA patients. Three variants were novel. Dual-luciferase assays showed that six variants significantly altered promoter activity compared to wild-type (range 69.6%-82.3%). JASPAR prediction revealed that these variants affected binding sites for 16 transcription factors, including GATA1, GATA2, GATA3, STAT3, ZEB1 and E2F1. EMSA confirmed altered DNA-protein binding patterns for all six variants, and super-shift assays further validated that the g.24571 A > G variant specifically disrupts GATA3 binding. This is the first study to identify functionally relevant MEF2C promoter variants in PDA. Our findings suggest that dysregulation of MEF2C through promoter variants may contribute to PDA pathogenesis by disrupting critical transcription factor interactions. These results extend the genetic landscape of PDA beyond coding regions and provide new insights into the molecular mechanisms of CHD.

Mental health workforce research treats South Asian Americans as a single group, yet they speak many mutually unintelligible languages, and language concordance shapes whether people with limited English proficiency (LEP) reach and stay in care. We measured the availability, geographic concentration, and affordability of psychotherapists listing eight South Asian languages. We analyzed 347,464 Psychology Today directory profiles (2025), identified providers listing Hindi, Urdu, Punjabi, Gujarati, Bengali, Tamil, Telugu, or Nepali, and linked counts to American Community Survey (2019-2023) speaker and LEP populations. We computed listed providers per 100,000 speakers and per 100,000 LEP speakers, supply-need alignment, geographic concentration, and payment acceptance and session price. Of all therapists, 2,310 (0.66%) listed a South Asian language; 59.4% of them listed two or more. Listed availability per 100,000 LEP speakers ranged from 1,160 for Hindi to 22.8 for Nepali, and per 100,000 speakers from 213.7 (Urdu) to 7.6 (Nepali); provider shares were unevenly aligned with LEP shares (index of dissimilarity, 0.41). Of Nepali LEP speakers, 43.0% lived in a state with no provider listing Nepali, against 0.9% for Hindi, and the languages with the fewest listed providers had the largest LEP shares and most recent arrivals. Providers listing a South Asian language were more often out-of-network (adjusted odds ratio, 1.58; 95% CI, 1.31-1.92) and charged $3.90 more per session (95% CI, 1.16-6.64). Language differences in listed provider availability within the South Asian population are large and invisible in aggregated data, pointing to the need for disaggregated data systems, language-specific workforce development, and affordability policy.