Bile acids that induce immunosuppression through activation of the Takeda G protein-coupled receptor 5 (TGR5) have recently been identified in the circulation of patients with liver failure and sepsis. These bile acids are associated with increased susceptibility to infection and a high short-term mortality. Furthermore, TGR5 activation by bile acids has been implicated in the development of pruritus. However, therapies targeting TGR5-activating bile acids in patients have not yet been reported. This study investigates the effects of two artificial liver support systems, the Molecular Adsorbent Recirculating System (MARS) and the open albumin dialysis (OPAL). Proof of concept study, multicenter study. University Hospital Jena, University Hospital Ulm, and University Hospital Münster, Germany. Patients with severe liver failure, as defined by the Sequential Organ Failure Assessment hepatic sub-score (i.e., bilirubin > 12 mg/dL). Patients with severe liver failure were randomized to receive one session of MARS or OPAL for 8 hours, followed by crossover to the other treatment on the next day. Bilirubin, circulating total and individual bile acids, albumin function, and TGR5 activation induced by circulating bile acids were assessed before and after each treatment session. Both OPAL and MARS significantly removed bilirubin, as well as individual and total bile acids from circulation. OPAL was superior to MARS in removing protein-bound lipophilic bile acids and restoring patients' albumin function (i.e., albumin-binding capacity, detoxification efficiency, and binding efficiency). TGR5 activation induced by circulating bile acids was reduced by 60% with OPAL compared with 39% with MARS (median values, p = 0.051). Artificial liver support systems effectively remove immunosuppressive bile acids from circulation. The clinical implications of bile acid reduction, however, require further study.
Post-stroke cognitive impairment is common after acute ischemic stroke, yet early cognitive deficits are often underrecognized in routine care. Prolonged venous transit (PVT) on perfusion imaging reflects impaired venous drainage and has been linked to worse functional outcomes in large-vessel occlusion (LVO) stroke, but its relationship with early cognitive impairment remains unclear. In this retrospective study, we evaluated consecutive patients with anterior-circulation LVO who underwent baseline perfusion imaging and had a documented discharge Cog-4 score (derived from four NIHSS items: orientation, command following, language, and attention/neglect). PVT was defined as a Tmax delay ≥10 s within the posterior superior sagittal sinus or torcula. The primary outcome was discharge Cog-4 score. Among 253 patients, 85 (34%) had PVT. Patients with PVT had higher Cog-4 scores than those without PVT (median, 2 vs 0; P < 0.001). In multivariable linear regression adjusting for age, admission NIHSS score, occlusion laterality, and follow-up infarct volume, PVT remained independently associated with higher Cog-4 scores (β, 0.63; 95% CI, 0.07-1.2; P = 0.029). A multivariable model demonstrated good discrimination for identifying normal or minimal impairment (Cog-4 score 0-1) with an area under the curve of 0.86 (95% CI, 0.81-0.90). These findings suggest that venous outflow impairment on baseline perfusion imaging is independently associated with early cognitive dysfunction at hospital discharge and may serve as a practical imaging marker for early cognitive risk stratification in anterior-circulation LVO stroke.
Lost circulation, which refers to the unintended loss of drilling fluid into underground formations, presents a significant challenge in drilling operations. This issue often leads to considerable non-productive time and financial losses. To effectively address this problem, it is crucial to accurately predict loss zones, volumes, and the extent of fluid invasion. This study introduces an innovative approach by integrating petrophysical well logs with drilling operational parameters and mud characteristics within a machine learning framework. Using a comprehensive dataset of 246,620 data points from 73 wells in an Iranian oil field, we developed three advanced predictive models: multi-layer perceptron (MLP), Kolmogorov-Arnold network (KAN), and a novel hybrid MLP-KAN architecture. Performance evaluations revealed that the hybrid model significantly outperformed the standalone models, achieving a determination coefficient (R2) of 0.9445 and a root mean square error of 0.0143. In contrast, the standalone MLP model achieved an R2 of 0.9054, while the KAN model reached an R2 of 0.9075. The hybrid framework effectively identified three primary mud invasion zones within the field, located at depths of 1800-2000 m, 2300-2600 m, and 2800-3000 m, accurately quantifying their average invasion volumes and radii. SHAP analysis indicated that the most significant predictive features included sonic transit time (DT), bit size, mud weight, and calcium content, aligning the model's output with established principles of drilling physics. The findings from this research provide a robust and interpretable tool for proactive management of lost circulation, enabling operators to implement zone-specific prevention strategies, optimize drilling fluid programs, and notably reduce operational risks and costs. The framework enables proactive loss prevention through early zone identification and targeted mitigation strategies, offering a scalable solution for enhancing drilling efficiency and reducing operational risks. Overall, this work bridges the gap between data-driven analytics and practical field applications, offering a scalable solution for enhancing drilling efficiency.
Endovascular thrombectomy (EVT) is the standard of care for eligible patients with anterior circulation large vessel occlusion (LVO). The optimal anesthetic strategy during EVT for young adults with LVO remains unclear. Using target trial emulation, we performed a pooled analysis of individual patient data from the DEVT, RESCUE BT, and MARVEL trials. We compared anesthetic strategies (general anesthesia [GA] vs. non-GA [conscious sedation/local anesthesia]) during EVT in patients aged 18-50 years. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] 0-2). Secondary outcomes included ordinal mRS shift, excellent outcome (mRS 0-1), favorable outcome (mRS 0-3), successful reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] grade ≥2b), early neurological improvement (ENI), pneumonia, mortality, and symptomatic intracranial hemorrhage (sICH). Average treatment effects were estimated via inverse probability of treatment weighting (IPTW) and G-computation, with risk differences (RDs) and (common) odds ratios (ORs) reported. Among 284 included patients in the target trial, 94 received GA and 190 received non-GA. Non-GA was associated with higher rates of 90-day functional independence (mRS 0-2) compared to GA (RD 0.12, 95%CI: 0.02 to 0.25). GA was associated with increased pneumonia incidence (RD -0.21, 95%CI: -0.35 to -0.11). Additionally, reperfusion success, mortality, and sICH rates did not differ significantly between groups. In this emulated trial involving young stroke patients undergoing EVT, non-GA was associated with a higher likelihood of functional independence compared to GA with similar reperfusion success and sICH. These findings may inform anesthetic selection for young adults with anterior circulation LVO pending a dedicated randomized trial. ChiCTR.org.cn Identifier: ChiCTR-IOR-17013568; ChiCTR-IOR-17014167; ChiCTR2100051729.
Comprehensive mapping of drug-induced metabolic alterations is crucial for understanding the mechanisms of targeted therapies. Antibody-drug conjugates (ADCs) such as trastuzumab emtansine (T-DM1) have revolutionized targeted cancer therapy by combining antibody specificity with cytotoxic potency. However, the metabolic reprogramming underlying their therapeutic action and systemic effects remains poorly understood. Here, we applied high-performance liquid chromatography-mass spectrometry (HPLC-MS)-based metabolomics to profile tumor and plasma metabolic alterations in a human epidermal growth factor receptor 2-positive (HER2+) xenograft model at 4- and 7-days following T-DM1 treatment, corresponding to the period of pronounced antitumor activity. A total of 32 significantly altered metabolites were identified in tumor tissues, mapping to pathways including tricarboxylic acid (TCA) cycle, pyrimidine metabolism and lipid metabolism, reflecting disruption in energy production and macromolecular biosynthesis. In plasma, 12 significantly altered metabolites were identified, predominantly affecting histidine, glutamine, taurine, tryptophan, and tyrosine metabolism. Integrated analysis further revealed two compartment-specific metabolites-hippuric acid and uric acid-showing opposite trends, with elevated levels in tumors and reduced levels in plasma. These bidirectional changes indicate a metabolic coupling between tumor and circulation, driven by differential utilization and excretion processes during T-DM1 response. Collectively, our findings demonstrate that T-DM1 elicits coordinated local and systemic metabolic reprogramming, providing mechanistic insights into its antitumor activity and the metabolic coupling between tumor and circulation.
Huanglian Wendan decoction (HLWD) is traditionally used to treat a syndrome characterized by symptoms such as insomnia, irritability, and digestive disturbances. Its historical application in addressing phlegm-heat-induced mental and emotional disorders offers both a cultural and clinical basis for investigating its potential mechanisms in alleviating depressive symptoms via gut-brain axis. To explore the potential therapeutic mechanisms of HLWD in improving depression. Behavioral outcomes were assessed using the SPT, TST, OFT, and SIT. Neurogenesis was evaluated by measuring dendritic length and neuronal intersections. Allopregnanolone levels were measured using ELISA. Inflammatory signaling pathways (TLR4, MyD88, NF-κB) and cytokines (IL-1β, TNF-α, IL-10, IL-4) in the hippocampus were analyzed via WB. The integrity of the intestinal barrier was further validated through immunofluorescence and histological examination. Finally, GW6471 was employed to investigate whether PPAR-α mediates the effects of HLWD. The UPLC analysis identified 42 constituents, primarily comprising flavonoids, alkaloids, and coumarins. Behavioral assays demonstrated that HLWD effectively ameliorated depressive-like behaviors in mice. Mechanistically, HLWD elevated the levels of DCX-positive neurogenesis markers, inhibited microglial activation, protected the intestinal mucosal barrier, and reduced inflammatory responses in both the colon and hippocampus. The RNA-seq results indicated an enrichment of the PPAR signaling pathway in colon. Consistent with this finding, HLWD significantly upregulated both the protein and mRNA levels of PPAR-α in the colon. Meanwhile, it increased the concentration of allopregnanolone in hippocampal via peripheral circulation. Notably, the administration of the PPAR-α antagonist GW6471 reversed these neuroprotective effects and the associated protein changes, thereby underscoring the critical role of PPAR-α in the therapeutic mechanism of HLWD. HLWD can elevate the levels of PPAR-α and allopregnanolone in the colon, subsequently influencing the levels of allopregnanolone in the hippocampus via peripheral circulation. This process may enhance neurological function and alleviate depressive symptoms.
Despite restoration of systemic and pulmonary circulation and normalized oxygen saturation, patients with Fontan circulation experience frailty, exercise intolerance, and impaired exercise hemodynamics. Altered cytokine-chemokine profiles have been reported, but their relationship with Fontan pathophysiology remains poorly defined. Adult Fontan patients and matched controls were assessed for frailty, cardiopulmonary exercise capacity, and resting/exercise-augmented hemodynamics. Plasma cytokine-chemokine concentrations were measured using multiplex ELISA. Twenty Fontan patients (mean age 28.8 ± 9.8 years; 35% female) and 20 controls (29.7 ± 6.0 years; 30% female) were studied. Fontan patients had slower 5× sit-to-stand times (9.6 ± 3.1 vs. 5.7 ± 1.3 sec; p<0.0001), lower VO₂max (% predicted), and reduced stroke index, cardiac index, and cardiac power index. TNF-α, IL-1β, IL-6, IFN-γ, IL-8, IP-10, MCP-1, and SDF-1α were elevated in Fontan patients, while IL-10 and MIP-1α were not different. SDF-1α and IP-10 correlated with frailty, impaired oxygen uptake, and hemodynamic parameters. Elevated SDF-1α and IP-10 are associated with frailty and impaired exercise hemodynamics in Fontan patients. These novel findings suggest a role for inflammation in Fontan-associated dysfunction and warrant further investigation.
Zoos may serve as sentinel sites for zoonotic vector-borne diseases. West Nile virus (WNV) and Usutu virus (USUV) are closely related orthoflaviviruses transmitted between Culex mosquitoes and a bird reservoir. Both viruses can also infect mammals, including humans, where they may cause symptoms and, more rarely, hospitalization and death. However, serological cross-reactivity between WNV and USUV complicates their differential diagnosis. Here, we aimed to reconstruct the dynamics of emergence of WNV in a zoo located in a newly affected area in Europe, using ELISA and Virus Neutralization Test (VNT) serological analysis of 1707 animal sera collected between 2015 and 2024. Combining this data in a model accounting for cross-reactivity with USUV, we estimated yearly forces of infection (FOI) by both viruses, and thus found that WNV likely circulated in the area one year prior to the first cases reported to the passive surveillance system. Our results also showed that, in the zoo, mammals and reptiles had a lower risk of infection than birds (relative risk of 0.14 [0.05; 0.28]), and that the exposure of birds to water (aquatic lifestyle or proximity to stagnant water) affected the risk. Finally, we estimated diagnosis parameters, including the sensitivity of the VNT (80.4% [76.5%; 84.3%]), the expected VNT titer value, and the level of serological cross-reactivity between viruses during the VNT. To conclude, our modelling framework allowed to disentangle the co-circulation of two closely related viruses, a crucial point in ensuring the reliable sentinel surveillance of these vector-borne zoonotic pathogens.
Conventional nanocarriers often face challenges of insufficient tumor specificity and poor cellular internalization. To overcome these limitations, we developed an all-in-one prodrug nanoplatform based on hyaluronic acid (HA) that synergistically integrates active targeting, pH-responsive charge reversal, and controlled drug release. Doxorubicin (DOX) was covalently conjugated to oxidized HA via a pH-sensitive imine bond, while a charge-reversal polymer (PLL-DMMA) was grafted onto the HA backbone. This design enables CD44-mediated active targeting toward cancer cells. Crucially, the nanoplatform exhibits a smart charge-reversal characteristic: maintaining a negative surface charge (-32.8 mV) at physiological condition (pH 7.4) for extended circulation, while switching to positive (+16.5 mV) in the acidic tumor microenvironment (pH 6.5) to enhance cellular uptake. In vitro studies demonstrated significantly improved internalization in CD44-overexpressing MKN-45 cells compared to SNU-216 cells with low CD44 expression. The release profile showed high stability at pH 7.4 (<5% release in 5 days) and rapid drug release at endo/lysosomal pH (61.6% at pH 5.0). Cytotoxicity assays confirmed enhanced efficacy of the charge-reversed formulation, with lower IC50 values in both cell lines. This multifunctional prodrug nanoplatform represents a promising strategy for precision cancer chemotherapy through synergistic enhancement of tumor targeting and intracellular drug delivery.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, yet conventional chemotherapy is limited by poor tumor specificity and severe toxicity. Cantharidin (CTD), a natural antitumor agent, is hindered by nephrotoxicity and hepatotoxicity. This study aimed to construct a dual-ligand-modified CTD-loaded solid lipid nanoparticle (GA-FA-CSLNs) using 18-glycyrrhetinic acid (GA) for hepatocyte targeting and folate-PEG3500-DSPE (FA) for long circulation, and to evaluate its antitumor efficacy, mechanism, and safety. GA-FA-CSLNs were prepared by emulsification-ultrasonication and optimized via Box-Behnken design. The nanoparticles were characterized. In vitro antitumor activity was assessed in Huh-7 cells using CCK-8, flow cytometry, and Western blotting. In vivo efficacy and safety were evaluated in Huh-7 tumor-bearing nude mice, and pharmacokinetics in SD rats. GA-FA-CSLNs exhibited favorable physicochemical properties. In vitro studies showed enhanced cellular uptake, the lowest IC50, and 43.2% apoptosis in Huh-7 cells. Mechanistically, GA-FA-CSLNs downregulated Eph receptor B4(EphB4) and Bcl-2, while upregulating caspase-3 and Bax. In vivo, the tumor inhibition rate reached 58.67%, superior to free CTD and sorafenib, with 100% 14-day survival and no significant abnormalities in serum biochemistry or histopathology. Pharmacokinetic analysis showed prolonged elimination half-life (2.54 h) and a 3.2-fold increase in area under the blood concentration-time curve versus unmodified CSLNs. GA-FA-CSLNs represent a promising actively targeted nanoplatform that enhances CTD antitumor efficacy against HCC via EphB4 pathway inhibition while reducing systemic toxicity, offering a potential strategy for targeted HCC therapy.
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) represent the most investigated type of "immunosuppressive" neutrophils in humans. However, a detailed understanding of human PMN-MDSCs has been hindered for years by limited knowledge of their specific markers for sorting and purification, as well as by their very low numbers in patient circulation. Recently, the use of advanced technologies has shown that human PMN-MDSCs are generated during emergency granulopoiesis and comprise a heterogeneous population of both immature and mature neutrophils. It has also been shown that human mature PMN-MDSCs (mPMN-MDSCs) perform immunosuppressive functions through transcriptional reprogramming during maturation. Furthermore, single-cell RNA sequencing experiments have shown that human mPMN-MDSCs and tumor-associated neutrophils (TANs) share transcriptomic similarities, therefore uncovering a potential relationship between them. In this Perspective, we discuss: i) how our knowledge on human PMN-MDSCs has advanced; ii) the criteria for discriminating human PMN-MDSCs from normal neutrophils or other immunosuppressive neutrophil populations; iii) recent findings revealing that human mPMN-MDSCs exhibit transcriptomic features suggestive of functions beyond immunosuppression.
Blood blister-like aneurysms (BBAs) are rare, fragile vascular lesions most commonly arising from non-branching segments of the internal carotid artery. Basilar artery BBAs are exceptionally uncommon and present significant diagnostic and management challenges. We report the case of a woman in her late 50s who presented with sudden-onset occipital headache, neck stiffness, and subarachnoid haemorrhage. Digital subtraction angiography identified a 3 mm blister-like aneurysm in the basilar artery, considered the presumed culprit lesion, along with an incidental basilar artery fenestration. Endovascular flow-diversion was recommended; however, the patient declined intervention after informed counselling and was managed conservatively with intensive neurocritical monitoring. The patient recovered without residual neurological deficit. This case highlights the diagnostic overlap between aneurysmal and perimesencephalic subarachnoid haemorrhage, the importance of careful vascular imaging, and the management challenges posed by rare posterior circulation BBAs and associated vascular variants.
Accurate and rapid pulse assessment during cardiopulmonary resuscitation (CPR) is essential to minimize interruptions in chest compressions. Manual arterial palpation (MP) is subjective and often unreliable. This is especially true in low-flow states. Transesophageal echocardiography (TEE) enables continuous intra-arrest cardiac visualization. It may facilitate faster decision-making during pulseless arrest. To compare pulse evaluation-related decision-making time during CPR using TEE versus MP and to explore associated resuscitation outcomes. This prospective observational study enrolled adult patients (≥18 years) with non-traumatic in-hospital cardiac arrest in a tertiary emergency department. Pulse assessment during CPR was performed either by MP or intra-arrest TEE. The method depended on the treating physician's clinical judgment. The primary outcome was the time spent on pulse evaluation-related decision-making. This was defined as the time from initiation of pulse assessment to the decision to continue or stop chest compressions. Secondary outcomes included total CPR duration and the rate of return of spontaneous circulation (ROSC). These were considered exploratory. Nonparametric statistical tests were used as appropriate. A total of 112 patients were included (median age 75 years; 39.3% female). Pulse evaluation-related decision-making time was significantly shorter in the TEE group compared with the MP group (median 2 [2-3] vs. 7 [5-8] s; p = 0.001). Total CPR duration was also shorter in the TEE group (median 15 [6-65] vs. 30 [2-72] min; p = 0.005). A higher proportion of ROSC was observed in the TEE group; however, this finding should be interpreted strictly as exploratory and hypothesis-generating. Moreover, the study was not powered to establish causality. Intra-arrest TEE was associated with significantly shorter pulse evaluation-related decision-making times compared with MP during CPR. By enabling rapid, continuous cardiac assessment, TEE reduced time to pulse evaluation-related decision-making. These findings are exploratory; their impact on clinically meaningful outcomes remains uncertain. Observed differences in ROSC should be interpreted cautiously. Confirmation in randomized, multicenter trials is needed.
Secondary organic aerosol (SOA) constitutes a major fraction of fine particulate matter and poses substantial risks to human health, yet its sources and variability remain difficult to resolve in urban environments. Here, we investigate the processes driving episodic wintertime PM pollution in Seoul using winter 2022 measurements of non-refractory submicron aerosols (NR-PM1) from a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). Positive matrix factorization (PMF) resolved six organic aerosol (OA) factors, comprising four primary-like OA (POA) components-hydrocarbon-like OA (HOA), oxygenated hydrocarbon-like OA (OHOA), cooking OA (COA), biomass burning OA (BBOA)-and two oxygenated OAs (OOA1 and OOA2). Coupled analysis of OA factors and co-measured gaseous precursors indicates that POA accumulates under stagnant conditions, consistent with predominantly local emissions, whereas OOA is associated with aged aerosol in continental outflow, highlighting the importance of regional transport. In particular, OOA2 exhibits pronounced event-scale enhancements during high-PM episodes, while OOA1 maintains a persistent and baseline contribution under lower-PM conditions. Synoptic meteorological analysis further demonstrates that elevated OOA2 contributions occur under warm and humid air masses arriving via low-altitude southwest transport pathways. Concurrent increases in toluene and O3 during high-OOA2 periods support the co-transport of SOA precursors and enhanced chemical processing. Overall, these results show that wintertime SOA variability in Seoul is strongly modulated by synoptic circulation and transport pathways, underscoring the value of integrating aerosol composition, gas-phase chemistry, and meteorology to diagnose PM pollution in urban downwind regions.
Cerebral cysticercosis (CC), a neglected tropical disease of the central nervous system caused by Taenia solium larvae, is rarely associated with hydrocephalus in its parenchymal form. We report a 45-year-old male with a 20-year progressive course of cognitive decline, gait instability, urinary incontinence, and recurrent seizures. Epidemiological history included long-term rural residence, close contact with free-roaming domestic pigs, poor household sanitation, lack of standardized latrine use, and unsafe human feces disposal in the endemic region, together with consumption of undercooked pork two decades prior. Neuroimaging revealed multiple ring-enhancing parenchymal cysticercal lesions in the left frontal lobe, bilateral parietal lobes, right periventricular region, and right cerebellar hemisphere. The lesions were strictly parenchymal, periventricular, and adjacent to but not inside the third ventricle, with formation of a cerebral aqueductal septum, impaired cerebrospinal fluid (CSF) circulation, and supratentorial ventricular dilatation. The patient underwent ventriculoperitoneal (VP) shunting combined with staged albendazole therapy and antiepileptic treatment, achieving significant symptomatic improvement and seizure-free survival at one-year follow-up. This case underscores the unique pathogenesis of aqueductal septum formation in parenchymal neurocysticercosis, supports the efficacy of combined surgical and medical intervention in chronic presentations, and adds to the scarce literature on this rare comorbidity.
To describe institutional variation in use of cervical spine radiographs (x-ray) and computed tomography (CT) among children evaluated following blunt trauma. We conducted a planned secondary analysis of a multicenter, observational cohort study of children 0-17 years old evaluated for possible cervical spine injury (CSI) in 18 emergency departments (EDs) from December 2018-October 2021. Our primary outcome was any ED cervical spine x-ray or CT, and our secondary outcome was use of CT only. We performed univariable logistic regression, reporting ED-level unadjusted and injury severity adjusted proportions of children with any cervical spine imaging and CT only, stratified by presenting ED type (referring general ED vs pediatric ED). Severity adjustment was based on Pediatric Emergency Care Applied Research Network high-risk predictors (GCS 3-8, unresponsiveness, abnormal airway/breathing/circulation, and focal neurologic deficits). We enrolled 22,430 eligible children, of whom 17.9% (n=4,008) were referred from a general ED. Cervical spine x-ray or CT was performed in 52.9% (n=11,865) and 1.9% (n=433) were diagnosed with a CSI. After adjusting for severity, imaging proportions were similar within each ED type (referring general EDs and pediatric EDs). Among children whose initial evaluation occurred in a referring general ED, 71.3% underwent any cervical spine imaging and 32.3% underwent CT as the sole modality. Among children presenting directly to a pediatric ED, the corresponding proportions were 48.9% and 7.9%. In this observational study of children with potential CSI, those managed in referring general EDs and transferred to pediatric EDs more frequently underwent cervical spine imaging, including CT as the sole modality, than those presenting directly to pediatric EDs. These data can inform future benchmarking to assess concordance after implementation of the PECARN CSI decision rule.
Enteroviruses (EVs) are the major pathogens causing viral encephalitis and meningitis and frequently drive outbreaks in high-risk settings such as schools and healthcare facilities. We analyzed outbreaks reported from 1960-2025 to map epidemiology, clinical manifestations, and serotypes, informing prevention and control. We systematically searched Web of Science, PubMed, CNKI, and Wanfang from 1960 to July 1, 2025 using the keywords of enterovirus, encephalitis, meningitis and outbreak to assemble a global dataset of enterovirus encephalitis and meningitis outbreaks. Eligible studies must report outbreaks of laboratory-confirmed enterovirus meningitis or encephalitis, while those with unclear outbreak definitions or no laboratory confirmation were excluded. Standardized forms were used to extract information on outbreak characteristics, case demographics, and etiology data. A random-effects model was employed to derive combined estimates of attack rates, hospitalization rates, clinical manifestations and serotype distribution, with subgroup analyses by geographic region, temporal period, and age group. This research was registered in PROSPERO (CRD420251140412). A total of 56 outbreaks (28,622 cases) across 20 countries were included. Outbreaks were most prevalent in the Western Pacific and Europe, exhibiting seasonal peaks in June-July (Northern Hemisphere) and April-May (Southern Hemisphere), with a median size of 90 cases. Schools and medical institutions were the major outbreak settings. EV-B was the dominant species (94.6%, 53/56), with E30 being the most prevalent serotype. Two decades, 2000-2009 and 2010-2019, saw the highest number of reported outbreaks. The overall attack rate was estimated at 13.2% (95% CI 6.1-22.3). Notably, the pooled hospitalization rate was exceptionally high at 94.0% (95% CI 85.9-99.2). The most frequently reported symptoms were fever, headache, and vomiting. Enterovirus encephalitis and meningitis outbreaks remain a persistent global concern, marked by high hospitalization rates, summer-autumn peaks and regional patterns. They primarily affect children under 15 years old, with multiple serotypes in circulation. Shifting toward active syndromic and genomic surveillance, alongside targeted prevention in high-risk settings, is urgently needed. This work was supported by the Beijing Natural Science Foundation (L242052) and National Key R&D Program of China (2024YFC2310403); Jiangsu Province 333 Project.
Nonroutine discharge (NRD) from the hospital carries considerable cost. We identified predictors of NRD after surgical treatment of ruptured intracranial aneurysms (IAs). The American College of Surgeons National Surgical Quality Improvement Program database was searched for patients with surgically treated ruptured IAs from 2016 through 2020. Demographics, clinical characteristics, preoperative comorbidities, procedural details, and 30-day morbidity and mortality were extracted. NRD risk factors were determined by multivariate logistic regression. Surgical outcomes and postoperative complications were compared by aneurysm complexity and location after propensity score matching. Among 671 patients, 277 (41%) had NRD, 591 (88%) underwent emergent surgery, and 466 (69%) had complex aneurysms. After matching, complex aneurysms were associated with higher frequencies of postoperative pneumonia (16% vs 10%, p=0.04), NRD (45% vs 32%, p=0.01), and 30-day reoperation (21% vs 13%, p=0.03). Aneurysms in the vertebrobasilar circulation were associated with a higher frequency of postoperative urinary tract infection (13% vs 5%, p=0.01) and organ/space surgical site infection (4% vs 0.7%, p=0.02). On multivariable analysis, NRD was associated with age ≥65 years (odds ratio [OR] 2.76), Black/African American (OR 1.86) or White (OR 2.16) race, preoperative immunosuppressive or steroid therapy (OR 4.46), complex aneurysms (OR 1.75), emergent surgery (OR 2.37), length of stay ≥21 days (OR 2.94), and postoperative pneumonia (OR 3.64) or sepsis (OR 5.64). Predictors of NRD after ruptured IA surgery included patient demographics, aneurysm characteristics, and postoperative complications. Early identification of high-risk patients and targeted discharge planning could reduce NRD rates.
Non-invasive monitoring of deep-tissue physiological processes from the body surface is technically challenging due to rapid signal attenuation and severe motion artefacts, primarily caused by high contact impedance and mechanical mismatch in conventional electrodes. Here we directly spray-coat a biocompatible two-dimensional nanosheet ink onto the human body, forming microscopically conformal van der Waals thin films that are intrinsically stretchable and mechanically adaptive to non-Euclidean, hairy and dynamically evolving body surfaces, thereby creating electrically functionalized body surfaces. Compared with commercial solutions, the resulting electrically functionalized body surface exhibits substantially lower contact impedance and markedly reduced extrinsic motion artefacts, enabling reliable bioelectrical signal acquisition from irregular body surfaces and robust monitoring of biopotential and bioimpedance modulations associated with deep-tissue physiological processes, including blood circulation, muscle movement and brain activity. This technology advances capability for continuous, non-invasive monitoring of deep-tissue activities during routine body movements.
Type 2B von Willebrand disease (VWD) is a rare qualitative variant, accounting for approximately 5% of all VWD cases. It is characterized by increased affinity of abnormal von Willebrand factor (VWF) for the platelet glycoprotein Ibα receptor, resulting in enhanced clearance of both high-molecular-weight VWF multimers and platelets from circulation. The management of women with type 2B VWD during pregnancy and the postpartum period poses unique challenges due to complex hemostatic abnormalities, a high risk of bleeding complications, and a lack of evidence-based guidelines. A recent systematic review, international registry analysis, and global physician survey highlighted several unmet clinical needs in this population, including gaps in early diagnosis, prenatal counseling, pregnancy monitoring, and peripartum management. In response, the ISTH Scientific Subcommittees (SSCs) on von Willebrand Factor and on Women's Health Issues in Thrombosis and Haemostasis collaborated to develop consensus-based guidance for the management of type 2B VWD in pregnancy and postpartum. Using the Real-Time Delphi methodology, 14 international experts reviewed 26 initial statements on diagnosis, monitoring, and treatment. After two rounds of anonymous voting and revisions based on participants' feedback, consensus was achieved on 25 statements. These consensus statements, grounded in the best available evidence and expert opinion, aim to standardize care, guide management, and improve clinical outcomes for women with type 2B VWD during pregnancy and postpartum.