Memorial Hospital

Moyamoya disease (MMD) has a strong genetic basis, with the rare RNF213 p.Arg4810Lys variant (rs112735431) representing a major risk factor, while the broader genetic architecture and disease-relevant vascular cell types remain incompletely understood. We conducted a genome-wide association study in Japanese individuals (n=47 656; 401 MMD cases and 47 255 controls). Population-level features at MMD risk loci were examined by regional allele frequency and haplotype analyses. We performed single-nucleus RNA-seq of superficial temporal arteries from patients with MMD (n=3). Cell type-specific enrichment of genome-wide association study signals was assessed using the Single-Cell Disease Relevance Score. Endothelial signatures were validated by integration with publicly available single-cell data sets from controls (n=5) and immunohistochemistry for candidate markers (n=1). Beyond rs112735431, we identified a genome-wide significant signal in the HDAC9-TWIST1 region (rs12530920; P=3.3×10-14; odds ratio, 1.77). Conditional analysis on rs112735431 revealed a protective RNF213 missense variant, p.Asp1331Gly (rs8074015; P=3.7×10-9; odds ratio, 0.53), whose minor allele was mutually exclusive with rs112735431-A on haplotypes. Population analysis revealed geographic variation and extended haplotype structure of the rs112735431-A allele in Japan. Single-nucleus RNA-seq identified a mesenchymal-like endothelial cell (MEC) population with selective FN1 expression. Genome-wide association study-prioritized disease genes were strongly enriched in MECs. MECs showed mesenchymal pathway activation with a regulatory program distinct from canonical endothelial states. The proportion of MECs was markedly increased in MMD (72% versus 28% in controls), and fibronectin 1 (FN1) expression in endothelial regions was confirmed by immunohistochemistry. Our findings identify a protective RNF213 p.Asp1331Gly variant (rs8074015) that is mutually exclusive with the known rs112735431-A allele. Genetic risk converges on an MEC state markedly expanded in MMD.

Osteoporosis causes fractures which further increase the disease burden of rheumatoid arthritis (RA), however, osteoporosis treatment rates remain low. While several studies have reported that biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) can prevent or improve osteoporosis in RA, our large-scale, real-world study showed that 1 year-b/tsDMARDs use did not arrest osteoporosis progression. This study aimed to examine longer-term changes in bone mineral density (BMD). BMD was observed for up to 5 years in patients receiving b/tsDMARDs for active RA. The primary endpoint was change in BMD (T-score), and the secondary endpoint was change in T-score-related factors. In total, 797 patients (anti-osteoporosis (-), n = 645; anti-osteoporosis (+), n = 152) were included, with a median 3.1-year follow-up (2,489 patient-years). Clinical disease activity index (CDAI) improved in both groups (26.0/24.4 → 6.6/6.8). T-scores decreased significantly in the femoral neck and radius in the anti-osteoporosis (-) group but not in the anti-osteoporosis (+) group [anti-osteoporosis (-): mean change -0.11/-0.33, both p < 0.001; anti-osteoporosis (+):-0.01/-0.10, p = 0.830/0.071]. Overall, 460 patients (58%) experienced a decrease in T-score. A high baseline T-score correlated with a subsequent decrease, while longer osteoporosis treatment duration correlated with an increase. Unexpectedly, the duration of b/tsDMARD use and mean CDAI during observation were not associated with BMD maintenance. Even when RA activity was controlled with b/tsDMARDs, BMD still decreased. This study emphasizes the importance of considering osteoporosis as an independent aspect of RA, beyond inflammation control.

Endotoxic septic shock, a subset of septic shock with high endotoxin activity and multiorgan failure, is associated with high risk of death. We sought to identify the effect of endotoxin removal from the blood with polymyxin B haemoadsorption on mortality. We conducted an open-label, randomised, controlled, phase 3 trial at 19 US hospitals, enrolling adults (aged ≥18 years) with septic shock requiring vasopressors, with multiple organ dysfunction, and with endotoxin activity between 0·60 and 0·89 units. Patients were randomly assigned (2:1) to receive two sessions of polymyxin B plus standard of care or standard of care alone (control), with block randomisation stratified by site. Study personnel were masked to treatment allocation. Polymyxin B haemoadsorption was given via haemodialysis at a blood flow rate of 80-120 mL/min for 90-120 min per session, 22 h apart. The primary outcome was 28-day mortality in the intention-to-treat cohort. The safety cohort included all participants exposed to any amount of study treatment. Design and analysis followed a Bayesian framework, using a prior for the treatment effect based on a subgroup of the earlier EUPHRATES trial. 90-day mortality was the key secondary outcome. The trial was registered at ClinicalTrials.gov and is completed (NCT03901807). Between Sept 30, 2019, and April 10, 2025, we screened 14 890 patients, of whom 157 were enrolled (106 assigned to polymyxin B and 51 to control; 66 [42%] women and 91 [58%] men). At 28 days, 41 (39%) patients in the polymyxin B group and 23 (45%) in the control group had died, yielding a posterior probability of benefit of 95·3% (APACHE-II adjusted odds ratio 0·67 [95% credible interval 0·39-1·08]). At 90 days, the posterior probability of benefit was 99·4% (0·54 [0·32-0·87]). Of 100 patients in the polymyxin B group assessed for safety, 30 (30%) had a serious adverse event compared with 11 (22%) of 51 patients in the control group (difference -8 percentage points [95% CI -22 to 6]). Two (2%) serious adverse events in the polymyxin B group were treatment-related, one related to polymyxin B and one to catheter placement. In patients with endotoxic septic shock defined by high endotoxin activity and multiorgan failure, polymyxin B haemoadsorption was associated with a high probability of lower mortality at 28 days and 90 days. Spectral Medical.

The viscosity coefficient is a fundamental parameter in fluid dynamics and soft matter physics; however, conventional measurement techniques, including falling-ball, capillary flow, and vibrational methods, generally require large, homogeneous samples and are incompatible with microscale or optically scattering systems. Here, we report a single-fiber optical tweezers platform that utilizes a microcone-shaped fiber probe for stable, non-contact manipulation of microscale particles and quantitative viscosity probing. The tapered fiber tip, fabricated via controlled chemical etching and optimized through numerical simulations, promotes photonic nanojet formation at the fiber output, resulting in enhanced optical gradient forces and robust single-beam trapping. Experimental measurements demonstrate efficient trapping of 6 μm polystyrene microspheres, achieving a maximum trapping force of 24.9 pN and a trapping efficiency of 46.7%, in excellent agreement with theoretical predictions, thereby validating the underlying optical force model. In addition, the same platform was employed for in situ viscosity extraction from glycerol–water mixtures and whole blood. The measured values deviate by less than 4% from commercial viscometers across a broad dynamic range extending to 6.12 mPa s. These results demonstrate that nanojet-enhanced optical forces provide a compact, energy-efficient route for probing fundamental fluid properties at the microscale, while offering insight into light–matter interactions in complex fluidic environments.

Major adverse cardiovascular events (MACE) in patients with liver cancer receiving vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKI) remain uncertain. This retrospective cohort study aimed to evaluate the association between VEGF-TKIs and MACE and develop a risk prediction score. Using the Taiwan Cancer Registry linked with the Taiwan National Insurance Claim Database, 11,960 VEGF-TKI users were matched to 11,960 non-users by age and sex. Cause-specific hazard ratios (HRs) were estimated using multivariable Cox models with competing risk of non-cardiovascular death; propensity score (PS)-adjusted or PS-matched models were additionally conducted. During follow-up, the incidence of MACE was 49.5 versus 28.3 per 1,000 person-years in VEGF-TKI users and non-users. VEGF-TKI use was associated with increased MACE risk in multivariable analysis (adjusted HR 1.31; 95% CI 1.14-1.50); however, PS-adjusted and PS-matched models show non-significant associations. Because proportional hazards assumptions were violated, a 60-day landmark analysis was conducted, in which the increased risk was again significant across analytic approaches, including multivariable adjusted (HR 1.92; 95% CI 1.63-2.27), PS-adjusted (HR 1.35; 95% CI 1.00-1.82) and PS-matched models (HR 1.30; 95% CI 1.03-1.63). A point-based score was developed using a multivariable sub-distribution hazard model and assessed by a time-dependent c-index. The score demonstrated good discrimination with c-indices of 79.9% (3 months) and 74.2% (6 months). VEGF-TKIs were associated with increased risk of MACE among liver cancer patients. Landmark analyses indicated a persistently elevated risk among patients surviving beyond early treatment. A risk score based on prior cardiovascular history may help identify high-risk patients.

Cystic meningiomas are relatively rare and pose significant diagnostic challenges because their heterogeneous cystic architecture closely mimics gliomas or metastatic lesions. This radiological overlap creates critical diagnostic dilemmas that directly influence surgical strategy and patient counseling. We present two surgically treated cases that illustrate distinct imaging pitfalls and offer practical insights for advanced image-based differentiation. The first patient, a 45-year-old man, presented with behavioral changes and right-sided weakness; Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a heterogeneous left temporal cystic mass, initially suspected to be a cystic meningioma or metastatic tumor. The second patient experienced dizziness for one day following mild trauma; The CT and MRI showed cystic lesions at the left frontal convexity. The differential diagnoses included cystic meningioma, hemangioblastoma, metastatic tumor, brain abscess, and chronic subdural hematoma. Both patients underwent frontotemporal craniotomy, and the first case revealed a cyst containing xanthochromic fluid and distinct mural nodules attached to the dura. In the second case, the cystic component contained an organized mixed hematoma, liquefied “black oil” blood, combined with granulation tissue and a solid tumor mass. Histopathology confirmed angiomatous meningioma in the first case and atypical meningioma in the second. Despite the diagnostic complexities, both patients showed favorable postoperative recovery. These cases underscore the importance of distinguishing cystic meningiomas from other intracranial pathologies.

BackgroundPost-pull chest X-rays (ppCXR) are routinely performed after chest tube (CT) removal despite questionable utility. Prior studies suggest that ppCXR rarely alter management, but the impact of timing remains unknown. This study compares early vs delayed ppCXR on radiographic changes and clinical management in asymptomatic trauma patients. We hypothesized ppCXR timing may influence radiographic findings, but not reintervention rates.MethodsA retrospective study of trauma patients undergoing CT placement and removal at a level 1 trauma center from 2019 to 2022. Each ppCXR was classified as early (≤4h) or delayed (>4h). Primary outcome was reintervention after CT removal (CT replacement, VATS, or thoracotomy). Secondary outcomes included radiographic changes, unplanned ICU transfer, hospital and ICU LOS, and total CXRs.Results318 patients were included with a mean age of 47.2years, 25.2% female, and 77.4% with blunt mechanism. Most had delayed ppCXR (78.3%) with mean delay of 7.2h (2.3 vs 9.5h, P < .001). No differences were found in radiographic changes (26.1 vs 29.3%, P = .708) or reintervention (4.3 vs 5.6%, P = .999) between groups. Radiographic changes occurred in 28.6% of ppCXR, but these findings display poor sensitivity (65.0%) and specificity (73.4%) for reintervention. Delayed ppCXR had more ICU transfers (0 vs 5.6%, P = .046), but no differences in hospital LOS, ICU LOS, or total CXRs.DiscussionThe timing of ppCXR did not affect detection of radiographic changes or reintervention rates. Our findings support growing evidence questioning routine ppCXR in asymptomatic trauma patients. Future multicenter studies are warranted to establish standardized protocols and reduce unnecessary imaging in trauma care.

Schizophrenia is classified as a severe mental disorder. According to National Institute for Health and Care Excellence guidelines, psychotherapy should be the standard for treating schizophrenia, in addition to pharmacotherapy. Cognitive behavioural therapy since the early 1990s, thanks to scientific research, has confirmed its effectiveness in the treatment of schizophrenia. Nevertheless, in the literature on the subject, there are few descriptions of therapeutic work with pregnant women experiencing psychotic disorders in the course of schizophrenia. To present the process of psychotherapeutic treatment in the cognitive behavioural therapy trend in a patient diagnosed with schizophrenia and pregnancy over a concurrent period of time. The following paper focuses on the presentation of psychotherapeutic work in cognitive-behavioural therapy in pregnant women experiencing psychosis.

Pulmonary nodules are mostly solitary focal opacities typically round or oval in shape, with a diameter of less than 3 cm. They are surrounded by aerated lung parenchyma or located subpleurally, and are not associated with abnormalities, such as lymphadenopathy or atelectasis. Pulmonary nodules are found in up to one-third of computed tomography scans taken in adults, whereas they are significantly less common in children. In adult patients, incidentally detected pulmonary nodules are more frequently associated with neoplastic processes, while they are primarily related to congenital disorders or inflammatory conditions in paediatric populations. The identification of single or multiple pulmonary nodules should always prompt an attempt to determine the likely aetiology. The so-called idiopathic nodules, for which no definitive cause can be established, are a particular subgroup. Although the majority of these lesions are benign in children, some may represent an early stage of malignancy. Due to the lack of standardised management guidelines for the paediatric population, clinical decisions regarding follow-up and further diagnostic workup are often challenging. This literature review outlines the potential causes of incidentally detected paediatric pulmonary nodules, from malignant tumours to other diseases that can present in this form, and discusses methods for assessing the malignant risk of pulmonary nodules in paediatric patients. Finally, a management strategy is proposed for asymptomatic pulmonary nodules detected on imaging, computed tomography in particular.