In managing ECMO, preventing thrombus formation and hemolysis is crucial. While centrifugal pumps are increasingly used in pediatric ECMO, pumps designed for low flow range are not approved in Japan. Thus, centrifugal pumps for adults are used in pediatric ECMO cases. This increases the risk of thrombus formation in the enlarged flow paths before and after the centrifugal pump. To prevent thrombus formation in the ECMO circuit, it is necessary not only to appropriately optimize the dosage of anticoagulants but also to pay meticulous attention to circuit configuration. Furthermore, using centrifugal pumps at low flow rates increases shear stress on the blood, making hemolysis significantly more likely to occur in pediatric cases compared to adult cases. To reduce the incidence of hemolysis, it is necessary to use centrifugal pumps designed for low flow range. However, given the current situation where such centrifugal pumps are not approved in Japan, we must proceed with the understanding that hemolysis is more likely to occur in pediatric ECMO cases using centrifugal pumps. Moving forward, to reduce complications and improve outcomes in pediatric ECMO, the development of pediatric ECMO systems, including centrifugal pumps optimized for low-flow range, is required.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an autosomal dominant cerebrovascular disorder caused by NOTCH3 variants. Although more than 400 NOTCH3 variants have been reported, exon 20 variants remain rare, and clinical characterization is limited. We report a 39-year-old Chinese male with recurrent lacunar infarctions involving the brainstem, basal ganglia, and corona radiata. He had right-sided hemiplegia and cognitive deficits, without dizziness, headache, dysphagia, or dysarthria. His mother and maternal uncle had a history of ischemic stroke. Genetic testing identified a heterozygous NOTCH3 c.3313G > T (p.Gly1105Cys) variant in exon 20 (NM_000435.3), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria. Alongside adjusted medications for secondary stroke prevention, he received acupuncture and physical rehabilitation, followed by an improvement in mood and motor function. We also reviewed NOTCH3 exon 20 variants and found marked phenotypic heterogeneity across variants and populations. Migraine appears less frequent among Chinese carriers than in Western cohorts, whereas cognitive impairment may occur relatively early. Radiologically, temporal pole white matter hyperintensities were absent in our patient and other Chinese carriers of NOTCH3 variants in epidermal growth factor-like repeat (EGFr) domain 28, but reported in some with domain 27 variants. Although p.Gly1105Cys is located in a low-risk EGFr domain according to recent domain-based stratification models, our patient developed early-onset recurrent stroke, highlighting individual clinical variability. This case provides a detailed clinical and imaging description of CADASIL associated with NOTCH3 c.3313G > T (p.Gly1105Cys) and expands understanding of genotype-phenotype correlations among exon 20 variants.

Hypertension is the leading modifiable risk factor for cardiovascular diseases and affects over 1.3 billion adults. The renin-angiotensin and kallikrein-kinin systems (RAS and KKS) are critical in regulating blood pressure (BP). Clinically, the RAS and KKS have gained renewed importance, especially due to the discovery of the non-canonical vasodilative RAS pathway. Thus, for their clinical use, clarity on their measurement and reference ranges is essential. This systematic review aimed to synthesise the reported baseline circulating concentrations of RAS and KKS peptides, and the pre-analytical and analytical methods used in measuing them, in normotensive and untreated hypertensive adults. It adhered to PRISMA guidelines and synthesised data from 27 of 2864 retrieved studies that met the inclusion criteria. Reported peptide concentrations varied widely, ranging from 0.06-81.85 × 10³ fmol/mL. However, there was substantial heterogeneity across included studies in sample collection procedures, protease inhibitor use for peptide stabilisation, participant clinical phenotyping, BP reporting, and analytical methods. Reported levels of several RAS and KKS peptides were generally lower in hypertensive cohorts than in normotensive cohorts; however, these differences should be interpreted cautiously given the small number of hypertensive studies, incomplete BP reporting, and substantial heterogeneity across all included studies. Current evidence is insufficient to establish reference ranges for RAS and KKS peptides. This review emphasises the need for standardisation of sampling protocols, comprehensive peptide stabilisation, consistent clinical phenotyping, and robust analytical methods before RAS and KKS peptides can be used as clinical markers and their therapeutic potential identified.

Post-stroke dysphagia, which affects 40% to 70% of stroke survivors, frequently leads to aspiration pneumonia and diminished quality of life. Despite achieving a 98.8% initial swallowing screening rate, the nasogastric tube removal rate in our unit of 52.7% was below the national benchmark of 57.4%. A quality control circle root cause analysis was conducted, with five critical issues identified. These included a lack of routine in-service education, insufficient interdisciplinary collaboration, inconsistent screening tool versions being used, a deficit in integrated educational resources, and ambiguous re-screening protocols during patient transfers that resulted in a low re-screening rate (60.3%).

This project was implemented to increase the nasogastric tube removal rate in stroke patients from the baseline of 52.7% to a minimum target of 67.8%.

Four key interventions were implemented using quality control circle methodologies. These included: (1) Organizing interdisciplinary workshops to clarify intervention timing and professional roles across disciplines; (2) Integrating a "Three-Stage Swallowing Screening Tool" incorporating pre-procedural oral hygiene protocols and clinical decision-making algorithms; (3) Developing interdisciplinary patient education materials encompassing nursing, traditional Chinese medicine, and speech-language pathology; and (4) Revising standard operating procedures to mandate re-screening during all inter-unit transfers.

Post-intervention, the nasogastric tube removal rate increased from 52.7% to 69.9%, which exceeded the targeted goal. Notably, no re-intubations occurred within the six-month post-discharge follow-up period. In addition, the re-screening rate during inter-unit transfers improved markedly from 60.3% to 97.4%. Ancillary benefits included redirecting approximately 15 minutes of tube maintenance time per nurse daily into high-value individualized patient care,and an estimated savings in annual healthcare costs of NT$24,708 per family.

The process standardization and enhanced interdisciplinary synergy achieved under this project effectively eliminated gaps in care, resulting in substantially improved patient safety and care quality.

Maternal cardiac arrest occurs in 1 of 12,000 to 36,000 pregnancies and presents with unique etiologies and physiologic considerations. Pregnancy alters resuscitation dynamics, making key modifications to advanced cardiac life support protocols such as left uterine displacement, early and effective airway management, and consideration of perimortem cesarean delivery, crucial for successful resuscitation. Extracorporeal life support may be indicated in refractory cases and must account for unique maternal physiology, like increased oxygen consumption and cardiac output. Despite its complexity, maternal cardiac arrest can have favorable outcomes with timely multidisciplinary care, highlighting the importance of preparedness in maternal code response.

Thrombotic pulmonary and venous embolism remains a leading cause of maternal mortality in the United States, prompting expanded venous thromboembolism prophylaxis guidelines from organizations such as the American College of Obstetricians and Gynecologists, Royal College of Obstetricians and Gynaecologists, American College of Chest Physicians, and American Society of Hematology. Increased pharmacologic thromboprophylaxis, particularly with heparins, complicates decisions regarding neuraxial anesthesia due to the risk of spinal epidural hematoma, while general anesthesia carries higher maternal risks. Guidance from the Society for Obstetric Anesthesia and Perinatology and American Society of Regional Anesthesia and Pain Medicine supports individualized risk assessment.

Scorpion envenomation is an important public health problem in many tropical and subtropical regions and may result in rare but life-threatening grade III complications involving multiple organ systems. This systematic review synthesizes published articles from 2000 to 2025 that describe uncommon, severe clinical manifestations following scorpion stings. A total of 72 rare clinical complications were identified, encompassing cardiovascular, neurological, respiratory, renal, hematological, ocular, dermatological, and other systemic manifestations. Cardiovascular complications were the most frequently reported, whereas neurological complications exhibited the greatest clinical diversity. Mesobuthus tamulus and Hemiscorpius lepturus were most commonly associated with severe complications, and children younger than 10 years appeared to be at increased risk of serious neurological involvement. These findings highlight the remarkable clinical heterogeneity of grade III scorpion envenomation and emphasize the importance of early recognition, species-specific clinical awareness, and timely management to reduce severe outcomes in endemic regions.

The long-term health effects of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) remain unclear. Most importantly, it is highly controversial whether GIP agonists vs. antagonists should be developed and what their effects and/or potential side effects would be in the clinic. Further investigation is needed to explore the effects of GIP lowering alone or in combination with GLP-1 enhancing. Tree-structured phenotypic modeling (TreeWAS) and factorial Mendelian randomization (MR) analyses are valuable in this context, even though the highest circulating GLP-1 levels may reflect only a minimum activation i.e. levels achieved with pharmacological intervention with dipeptidyl peptidase 4 (DPP-4) inhibitors and not GLP-1 receptor agonists (GLP-1 RAs) which achieve much higher levels.

TreeWAS was first conducted to map associations of GLP-1 or GIP levels with a broad range of disease outcomes among 385,917 UK Biobank participants. Disease-trajectory analysis was applied to characterize temporal patterns of co-occurrence of multiple comorbidities related to GLP-1 or GIP or both. Subsequently, factorial MR was performed to investigate the joint effects of GLP-1 and GIP on the associated health outcomes. Finally, mediation analysis was employed to explore the underlying mechanisms through which GLP-1 and GIP exert their effects.

TreeWAS analysis revealed associations of elevated genetically predicted GLP-1 levels, even within the normal range, with decreased risk of metabolic diseases (e.g. type 2 diabetes) and polyarthropathies (e.g. gout). While genetically determined low GIP levels were linked to reduced risk of obesity, metabolic diseases (e.g. disorders of lipoprotein metabolism and other lipidaemias), digestive/hepatic and cardiometabolic diseases. Consistently, disease-trajectory analysis identified four major comorbidity clusters among individuals with genetically proxied physiologically lower GLP-1 and higher GIP levels, primarily involving metabolic diseases (e.g. type 2 diabetes), musculoskeletal system diseases (e.g. gout), gastrointestinal and urinary system disorders. Furthermore, the combined exposure to genetically predicted higher GLP-1 and lower GIP levels were associated with complementary and additive reductions in the risk of obesity (HR = 0.93, 95%CI: 0.88-0.99, p = 0.018), CVD (HR = 0.97, 95%CI: 0.94-0.99, p = 0.021), venous thromboembolism (VTE) (HR = 0.91, 95%CI: 0.83-1.00, p = 0.039), and multiplicative effects on composite hepatic events (CHEs) (HR = 0.88, 95%CI: 0.77-0.99, p = 0.040). No side effects on bone metabolism were identified. Finally, mediation analysis revealed that genetically predicted lower physiological GIP levels were associated with lower risk of obesity, CVD, VTE, overall and cardiovascular-specific mortality, with body weight consistent with a potential mediating role in exploratory decomposition analyses.

Our genetic findings are consistent with the hypothesis that GLP-1 levels in the higher physiological range and GIP levels in the lower physiological range, individually and jointly, may be associated with lower body weight and improved cardiometabolic and liver phenotypes, while these observations warrant mechanistic and clinical investigation.

Köhlmeier-Degos disease (Degos disease [DD]) is a rare vasculopathy with characteristic skin lesions and life-threatening gastrointestinal and cerebrovascular involvement. Although DD is often viewed as a thrombo-obliterative disorder, its immunopathology remains poorly defined. Here, single-cell RNA and T cell receptor sequencing of skin, blood, and cerebrospinal fluid from DD patients reveal pervasive type I and type II interferon activation, with an interferon-γ-biased program compared with systemic lupus erythematosus. Cytotoxic CD8A⁺ T cells show interferon-responsive activation and restricted clonotypic diversity, implicating cellular immunity in the DD inflammatory landscape. In a single-patient interventional study, JAK inhibition with ruxolitinib is associated with suppression of interferon-responsive programs, improvement of cutaneous inflammation, and stabilization of neurological disease. These findings support DD as an interferon-driven inflammatory vasculopathy and provide a rationale for further evaluation of interferon-JAK-STAT signaling. This study has been registered at ClinicalTrials.gov (NCT05998395).

Transplant-associated thrombotic microangiopathy is a severe and often fatal complication of allogeneic hematopoietic cell transplantation; early identification of the involved mechanisms may enable timely therapy.

Adult recipients of allogeneic hematopoietic cell transplantation (n = 195) were studied in the early post-transplant period. The recent harmonizing criteria from the world's leading blood and marrow transplant societies, such as ≥4 of 7 specific clinical/laboratory features for thrombotic microangiopathy diagnosis were applied. Plasma levels of sC5b-9, a marker of complement activation, was measured by an enzyme-linked immunosorbent assay and complement-related genes in blood cells were evaluated by both rapid genomic analyses using nanopore sequencing and conventional methods (targeted next generation sequencing and multiplex ligation-dependent probe amplification assay).

Ten patients who met ≥4 criteria (confirmed transplant-associated thrombotic microangiopathy) had high 1-year non-relapse mortality (60%) and high complement activation. In this group, plasma levels of sC5b-9 were higher than in patients without confirmed disease (p-value = 0.04) and normal controls (p-value <0.001). At the same time (after full chimerism), they showed seven rare variants of complement related genes (minor allele frequency <0.03). Rapid genomic analysis identified these alterations with complete concordance to conventional methods.

These results support the utility of applying harmonized criteria for early diagnosis of transplant-associated thrombotic microangiopathy and performing rapid genomic analysis with nanopore sequencing for the identification of variants in complement-related genes within 72h. Future studies on larger cohorts could explore the integration of rapid genomic analysis in this patient population and potentially for screening donors whose cells may carry genetic alterations for real-time clinical decision making.