OBJECTIVE:Endovascular thrombectomy (EVT) has been recommended as first-line therapy for patients with acute large-core ischemic stroke, yet the mortality remains high. We aimed to identify independent predictors of death within 90 days after EVT in this population. METHODS:This is a multicenter cohort study across 38 Chinese comprehensive stroke centers (November 2021-February 2023). Acute ischemic stroke patients with anterior circulation large vessel occlusion with ASPECTS ≤5, who underwent EVT were included. Independent mortality predictors of 90-day mortality were identified using multivariate logistic regression. RESULTS:Among 490 eligible patients with large core infarct included in this analysis, 205 (41.8 %) died within 90 days. In multivariable analysis, advancing age (adjusted OR 1.04, 95% CI 1.02-1.06; p < 0.001), admission hyperglycemia (adjusted OR 1.22, 95% CI 1.12-1.33; p < 0.001), higher NIHSS score on admission (adjusted OR 1.10, 95% CI 1.04-1.15; p < 0.001), lower ASPECTS on admission (adjusted OR 0.74, 95% CI 0.64-0.86; p < 0.001), unsuccessful reperfusion (eTICI<2b; adjusted OR 0.78, 95% CI 0.67-0.91), lower mTICI grade (p = 0.002), and poor collateral status (ASITN/SIR grade ≤2; adjusted OR 0.61, 95% CI 0.47-0.78, p <0.001) were independently associated with an increased risk of death within 90 days. SICH (p = 0.012), herniation (p < 0.001) and craniectomy (p = 0.001) were identified as independent in-hospital clinical predictors of mortality. CONCLUSIONS:In addition to non-modifiable factors (age and baseline stroke severity), admission hyperglycaemia, reperfusion success and collateral status are key modifiable predictors. Early intervention of cerebral edema and hemorrhagic complications may improve survival in this high-risk population.
Over 95% of Alzheimer's disease (AD) is caused by a complex mixture of genetic and environmental factors. This is called sporadic AD or late-onset AD, and much of its pathological mechanisms remain unclear. There is growing evidence indicating that the viral infection, such as herpes simplex virus type 1 (HSV-1), triggers and worsens the AD progression in combination with the APOE4 genotype in AD patients. The innate immunity of host cells produces proinflammatory cytokines, which further drive neuroinflammation in the brain. Concurrently, Aβ and phosphorylated tau could entrap foreign pathogens such as HSV-1 according to the "antimicrobial protection hypothesis of AD," and accelerate the progression of AD. In this review, growing evidence ranging from HSV-1 infection to the AD progression via the accumulation of Aβ and tau, and neuroinflammation is explored.
BACKGROUND:Approximately 100 cases of amusia have been documented to date. However, the neural mechanisms underlying amusia remain insufficiently understood. AIMS:This narrative review aims to synthesize existing literature on amusia, with a particular focus on reported cases of "pure acquired amusia" which means the acquired selective impairment of music processing in the brain. METHODS:The clinical characteristics of documented cases with pure acquired amusia were comprehensively reviewed and summarized. Furthermore, common lesion sites were identified by analyzing the lesion data from cases, and the crucial regions for music processing was estimated. RESULTS:Eleven cases with pure acquired amusia were identified. Analyses of symptoms and lesion sites revealed following things: first, most of cases with pure acquired amusia was caused by right hemisphere lesion. Second, there are three brain regions which damaged in many cases, that is superior temporal gyrus, insula, isthmus, and temporal pole. Third, until now, pure cases with musical alexia and/or agraphia have not been reported. CONCLUSION:These findings suggest that there are some brain regions which play a crucial role in music processing: the right superior temporal gyrus, the isthmus, the insula, and the temporal pole.
INTRODUCTION:Reports of late onset neuromyelitis optica spectrum disorder (NMOSD) cases have been accumulating. The Noto Peninsula areas exhibit a considerably higher aging rate compared to urban centers, potentially serving as an early example of aging-related challenges in NMOSD care in Japan. This study aimed to elucidate the demographic and clinical characteristics associated with aging in NMOSD patients in the Noto Peninsula areas. METHODS:A retrospective, single-center analysis was conducted on patients diagnosed with NMOSD and treated at Kanazawa Medical University Hospital between January 2009 and December 2024. RESULTS:The mean age at onset among patients residing in the Noto Peninsula areas (n=10) was 63.0 years, significantly higher than the 41.9 years observed in patients from the Kanazawa City and surrounding areas (n=8, p=0.034). Moreover, age at onset showed a significant upward trend over the years (03c1;=0.636, p=0.005). At the final observation, vascular risk factors were identified in 11.1-38.9% of patients, with hypertension notably prevalent among those with onset at age 70 years or older (75%, p=0.028). The mean number of medications at last follow-up was 7.9 (4 - 11), with no significant difference across age-at-onset groups. CONCLUSIONS:The age at NMOSD onset has exhibited a progressive increase over recent years, most markedly within the Noto Peninsula areas, likely reflecting demographic shifts such as declining birthrates and population aging. Advances in immunotherapeutic regimens have extended patient longevity, thereby contributing to an aging NMOSD cohort. Consequently, age-associated complications, including vascular risk factors and polypharmacy, are becoming increasingly prevalent.
BACKGROUND:The pathogenesis of diabetic neuropathic pain (DNP) remains unclear, with neuroinflammation mediated by abnormal TNF-α/NF-κB pathway activation being a key factor. This study aims to elucidate how this pathway contributes to DNP. METHODS:miR-33a-5p levels were measured via qPCR in the serum of diabetic patients and in cell models. Its diagnostic value for DNP was assessed using ROC and logistic regression. A high-glucose HMC3 microglia model was established. TNF-α and NF-κB levels were quantified by ELISA. Cell proliferation and oxidative stress were evaluated. The targeting relationship between miR-33a-5p and SIRT6 was confirmed by dual-luciferase assay, and their regulatory effects on TNF-α and NF-κB expression were examined. RESULTS:miR-33a-5p was significantly elevated in DNP patients (p < 0.001) and correlated positively with HbA1c (p < 0.001), demonstrating strong diagnostic value (AUC = 0.906, p < 0.001). DNP was associated with higher miR-33a-5p expression, in addition to its association with HbA1c levels. In vitro, high glucose upregulated miR-33a-5p (p < 0.01), NF-κB (p < 0.001), and TNF-α (p < 0.001) in microglia. Mechanistically, miR-33a-5p targets SIRT6, activating the NF-κB/TNF-α/p38MAPK pathway and worsening oxidative stress (p < 0.001). Inhibiting miR-33a-5p or overexpressing SIRT6 alleviated microglial activation and inflammation (p < 0.01). CONCLUSION:miR-33a-5p aggravates DNP by regulating SIRT6 and enhancing TNF-α/NF-κB signaling; its inhibition may reduce neuroinflammation and pain.
OBJECTIVE:This study aimed to identify plasma protein biomarkers associated with the presence and prognosis of intracerebral hemorrhage (ICH) in young adults. METHODS:We conducted a plasma proteomic analysis to identify differential proteins (DEPs) in an exploratory cohort, consisting of young spontaneous intracerebral hemorrhage patients (YSICH, N=24), and a control group (N=26: Cranial trauma patients, CT-Ctrl n=15; Brain tumor patients, BT-Ctrl n=11). Potential biomarker was then selected from these differential proteins based on fold change(FC), machine learning algorithms and previous studies. The level of this biomarker was validated using ELISA kits in an independent validation cohort, consisting of young spontaneous intracerebral hemorrhage patients (YSICH, N=144), and geriatric spontaneous intracerebral hemorrhage patients (GEICH, N=144). RESULTS:Within the exploratory cohort, 112 DEPs were significantly associated with YSICH and Desmoplakin (DSP) emerged as a key biomarker (p=0.007, FC=0.434). In the validation cohort, plasma DSP levels in young patients were significantly lower than in elderly patients (p < 0.001), demonstrating good discriminative ability for early-onset ICH susceptibility (AUC = 0.805, 95% CI: 0.750 to 0.861). Moreover, combining DSP with the ICH score improved prognostic accuracy, with the AUC value increasing from 0.795 to 0.828 (ΔAUC = 0.034), compared to using the ICH score alone. Notably, subgroup analysis revealed that this prognostic utility was highly specific to young patients presenting with mild-to-moderate clinical severity. CONCLUSION:Reduced plasma DSP levels reflect a susceptibility to early-onset ICH. Furthermore, DSP represents a promising adjunctive biomarker for prognostic risk stratification, particularly in young patients with mild-to-moderate disease severity.
BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder whose diagnosis is complicated by clinical overlap with neurodegenerative diseases. Fluid biomarkers may provide insight into disease mechanisms and support differential diagnosis.MethodsWe performed a small exploratory study at the Neurology and Neurosurgery Sections of the University Hospital of Perugia, between 2024 and 2025, comparing cerebrospinal fluid (CSF) and plasma biomarkers among patients with iNPH, Alzheimer's disease (AD), Parkinson's disease (PD), and non-neurodegenerative controls (CTRL). CSF concentrations of amyloid-β peptides (Aβ42, Aβ40, Aβ42/Aβ40 ratio), tau proteins (p-tau 181 and t-tau) and neurofilament light chain (NfL) were measured. In plasma, amyloid-β peptides (Aβ42, Aβ40, Aβ42/Aβ40 ratio), tau proteins (p-tau 217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed. Both CSF and plasma biomarkers were measured using standardized immunoassays. Group differences and correlations between CSF and plasma biomarkers were analyzed.ResultsCSF Aβ40 levels were significantly lower in iNPH compared with all other groups (all p < 0.005), and showed preliminary apparent discrimination for iNPH, requiring external validation, with an AUC of 0.95, sensitivity of 95%, and specificity of 86% at a cut-off of 9,327.5 pg/mL. AD patients were clearly distinguished from iNPH and the other groups by AD-specific changes in fluid biomarkers. CSF Aβ42 levels were lower in iNPH than in CTRL (p = 0.001) and PD (p = 0.009), while CSF p-tau181 and t-tau were decreased compared with AD (p < 0.001) and CTRL (p ≤ 0.024). The CSF Aβ42/Aβ40 ratio remained preserved in iNPH, distinguishing it from AD (p < 0.001).Plasma NfL correlated strongly with CSF levels in each diagnostic group, including iNPH (r = 0.77, p = 0.0012), whereas plasma amyloid biomarkers poorly reflected CSF concentrations.ConclusionsiNPH is associated with low CSF Aβ40 levels, possibly reflecting altered CSF dynamics rather than a primary pathophysiological mechanism. In iNPH, plasma NfL showed a preliminary correlation with CSF NfL; however, larger age-adjusted studies are required before peripheral markers can be considered clinically informative in this setting.
[This retracts the article DOI: 10.3389/fneur.2024.1391448.].
Purpose:Hearing loss (HL) has been increasingly recognized as a potential risk factor for cognitive decline and dementia. However, findings from existing meta-analyses remain heterogeneous. This umbrella review aimed to comprehensively synthesize current meta-analytic evidence on the association between adult hearing loss and cognitive outcomes. Methods:PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched from inception to 9 January 2026. Systematic reviews with meta-analyses examining the relationship between hearing loss and cognitive outcomes in adults were included. Methodological quality was assessed using AMSTAR-2. Evidence credibility was evaluated using the Ioannidis classification framework, and certainty of evidence was assessed using the GRADE approach. Overlap among primary studies across meta-analyses was quantified using the corrected covered area (CCA). Results:Nine meta-analyses were included. Hearing loss was significantly associated with increased risk of cognitive impairment (OR = 1.34, 95% CI: 1.17-1.53) and dementia (OR = 1.43, 95% CI: 1.21-1.68). In older adults, the associations were slightly stronger. Hearing loss was also associated with higher risk of Alzheimer's disease (OR = 1.66, 95% CI: 1.33-2.07). Evidence credibility was classified as highly suggestive for cognitive impairment and dementia. Conclusion:Adult hearing loss is significantly associated with increased risks of cognitive impairment and dementia. These findings highlight the importance of hearing health in cognitive aging and support further prospective and interventional studies.
Background:Rituximab (RTX) is increasingly used for refractory myasthenia gravis (MG), particularly muscle-specific kinase antibody-positive MG (MuSK-MG). However, the optimal dosing regimen remains to be standardized, and conventional high-dose protocols may increase treatment burden, cumulative exposure, and infection-related concerns. This study evaluated the clinical efficacy, safety, and immunological effects of a low-dose RTX regimen in patients with MuSK-MG. Methods:We retrospectively analyzed 35 patients with MuSK-MG who received low-dose RTX at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between January 1, 2017 and August 1, 2025. RTX was administered as 100 mg on day 1 and 500 mg on day 2, and the regimen was repeated every 6 months. All patients received at least two treatment cycles. Clinical outcomes were assessed using Myasthenia Gravis Activities of Daily Living (MG-ADL) scores at baseline and at 3, 6, and 12 months after treatment. Secondary outcomes included Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), adverse events, and peripheral CD19+ B-cell percentages in 24 patients. Results:The mean baseline MG-ADL score was 9.5 ± 5.6 and decreased to 2.1 ± 2.3 at 3 months, 1.0 ± 1.8 at 6 months, and 0.5 ± 0.9 at 12 months (all p < 0.001 vs. baseline). At 3, 6, and 12 months, 21 (60.0%), 25 (71.4%), and 28 (80.0%) patients achieved minimal manifestation status (MMS) or better was 6 months, respectively. Kaplan-Meier analysis showed a median time to MMS or better of 6 months. Both the bulbar involvement (BI) and non-bulbar involvement (non-BI) subgroups showed significant clinical improvement, although the trajectories of MG-ADL improvement differed between subgroups. In the 24 patients with available immunological data, the median CD19+ B-cell percentage decreased from 12.6% before treatment to 0.30% at 6 months (p < 0.001). Adverse events were mild, and no serious infusion reactions, severe infections, or hepatic or renal dysfunction were observed. Conclusion:Low-dose RTX was associated with rapid and sustained clinical improvement and effective peripheral B-cell depletion in patients with MuSK-MG, with acceptable tolerability. These findings support low-dose RTX as a potential therapeutic option for MuSK-MG, although prospective multicenter studies with standardized dosing and longer follow-up are needed.
Epilepsy is a globally prevalent chronic neurological disorder, and translocator protein 18 kDa (TSPO)-mediated neuroinflammation plays a critical role in epilepsy pathogenesis. This study aimed to explore the effect of the translocator protein 18 kDa antagonist ONO-2952 on neuroinflammation and cognitive function in epilepsy by establishing a mature epileptic rat model, which was divided into control group, untreated status epilepticus group and ONO-2952 intervention status epilepticus group; cognitive and behavioral tests were performed to observe the behavioral changes of rats, immunofluorescence staining was used to detect neuronal apoptosis, flow cytometry was adopted to analyze immune cell infiltration, and Western blotting was applied to measure the expression of proinflammatory cytokines. The results showed that ONO-2952 could down-regulate the expression of translocator protein 18 kDa, reduce the level of proinflammatory cytokines and peripheral immune cell infiltration, thereby inhibiting neuroinflammation in epileptic rats, and it could also relieve hippocampal neuronal apoptosis and effectively improve the cognitive dysfunction of model rats. This study confirms that ONO-2952 can regulate the expression of translocator protein 18 kDa, inhibit neuroinflammation and neuronal apoptosis, and improve cognitive function in epileptic rats, and further research is required to fully elucidate its specific biological effects.
Background:Collateral status is closely related to functional outcome after reperfusion therapy in acute ischemic stroke. Conventional single-phase computed tomography angiography (CTA) Tan score may be affected by scan timing and delayed collateral filling, whereas CTA reconstructed from computed tomography perfusion (CTP) source images provides time-resolved vascular information. This study compared conventional CTA Tan score with time-specific Tan-based collateral scores on CTP-derived CTA for predicting 90-day functional outcome. Methods:This single-center retrospective study included 104 stroke events from 103 patients with acute anterior circulation ischemic stroke who underwent intravenous thrombolysis and/or mechanical thrombectomy. Conventional CTA Tan score and CTP-derived CTA arterial-phase, arteriovenous-phase, and venous-phase time-specific Tan-based scores were assessed. The primary outcome was favorable functional outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. Logistic regression, receiver operating characteristic curve analysis, DeLong tests, treatment-stratified analyses, and exploratory thrombectomy sensitivity analyses were performed. Results:Sixty-two stroke events were associated with a favorable outcome. Forty-three events were treated with mechanical thrombectomy (37 direct thrombectomy and six bridging therapy), and 61 were treated with intravenous thrombolysis without subsequent thrombectomy. The areas under the curve for conventional CTA Tan score and CTP-derived arterial-phase, arteriovenous-phase, and venous-phase scores were 0.811, 0.811, 0.814, and 0.856, respectively. The venous-phase score showed the highest discriminative performance, although the overall difference compared with conventional CTA Tan score did not reach statistical significance (p = 0.079). In multivariable analysis, the venous-phase score remained associated with favorable outcome after adjustment for measured covariates. In the mechanical thrombectomy subgroup, the venous-phase score showed a higher AUC than conventional CTA Tan score (0.833 vs. 0.684; p = 0.004), whereas no significant difference was observed in the intravenous thrombolysis subgroup; however, the treatment-by-score interaction was not statistically significant (p = 0.788). Conclusion:The venous-phase Tan-based score on CTP-derived CTA may reflect delayed collateral filling and was associated with 90-day favorable outcome. Its AUC was numerically higher than that of the conventional CTA Tan score, but the difference was not statistically significant; incremental prognostic value remains to be confirmed. The mechanical thrombectomy subgroup finding should be considered exploratory and hypothesis-generating.
Background:Balloon guide catheters (BGCs) have demonstrated benefits in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), including improved recanalization rates and reduced distal embolization. The EMBOGUARD™ balloon guide catheter (Johnson & Johnson Neurovascular, Irvine, CA) represents a novel design with enhanced flexibility and compatibility with large-bore aspiration catheters. This study aims to evaluate the safety and efficacy of the EMBOGUARD™ BGC compared with non-BGC approaches. Methods:We conducted a retrospective multicenter study to analyze patients with AIS due to anterior large vessel occlusions (LVOs) who underwent MT between January 2022 and December 2024. Patients were divided into two groups: those treated with t☺he EMBOGUARD™ BGC and those treated without BGC. Primary outcomes included first-pass effect (FPE), successful recanalization (mTICI ≥2b), procedural time, number of passes, and distal embolization. Secondary outcomes included 90-day functional outcome (modified Rankin Scale [mRS] 0-2), mortality, and symptomatic intracranial hemorrhage (sICH). Results:A total of 178 patients were included (EMBOGUARD: n = 135, 75.8%; non-BGC: n = 43, 24.2%). The EMBOGUARD™ group demonstrated comparable rates of FPE (33.3% vs. 37.2%, p = 0.68) and successful recanalization (86.7% vs. 86.0%, p = 0.92). Procedural time was significantly shorter in the EMBOGUARD™ group (median 32 min vs. 49 min, p = 0.004). Distal embolization rates were similar between groups (4.4% vs. 4.7%, p = 1.00). The EMBOGUARD™ group showed significantly higher rates of favorable functional outcome at 90 days (48.6% vs. 28.1%, p = 0.04) and non-significantly lower 90-day mortality (13.7% vs. 16.7%, p = 0.6). Although favorably trending, multivariate logistic regression analysis did not confirm that EMBOGUARD™ was associated with greater odds of FPE (adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 0.65-6.41, p = 0.2), mRS 0-2 at 90 days (aOR 1.36, 95% CI 0.35-5.34, p = 0.7) or lower odds of mortality at 90 days (aOR 0.32, 95% CI 0.05-1.85, p = 0.2). Conclusion:The EMBOGUARD™ balloon guide catheter demonstrated comparable technical efficacy with reduced procedural times and improved clinical outcomes compared with non-BGC techniques in endovascular thrombectomy for acute ischemic stroke. These findings support the use of EMBOGUARD™ as a reasonable tool for flow arrest in stroke intervention.
Parkinson’s disease (PD) is characterized by progressive nigrostriatal degeneration, yet the contribution of modification-rich small RNAs to PD pathology remains unclear. Here, we used PANDORA-seq to profile the striatal small RNA landscape in a subacute MPTP-induced mouse model of PD. MPTP-treated mice exhibited significant motor deficits together with reduced striatal tyrosine hydroxylase and dopamine transporter expression, confirming successful model establishment. Small RNA profiling revealed that transfer RNA-derived small RNAs and ribosomal RNA-derived small RNAs, rather than microRNAs, dominated the striatal small RNA transcriptome. Among the dysregulated small RNA classes, mitochondrial tsRNAs showed the most prominent and coordinated downregulation. Bioinformatic analysis suggested that predicted targets of differentially expressed mt-tsRNAs were enriched in synaptic organization, presynaptic function, membrane contact sites, and lipid-related pathways. In SH-SY5Y cells, transfection of an mt-tsRNA mimic partially reversed MPP+ induced increases in reactive oxygen species and restored mitochondrial membrane potential. These findings provide a modification-aware small RNA landscape of the PD striatum and identify mt-tsRNA downregulation as a notable feature of MPTP-induced parkinsonism.
Background:Intracerebral hemorrhage (ICH) carries high mortality, with neuroinflammation driving adverse outcomes. The C-reactive protein (CRP)-to-albumin (ALB) ratio (CAR) and interleukin-6 (IL-6) are promising neuroinflammatory markers for acute brain injury, yet their combined value for evaluating ICH injury severity and 28-day mortality prediction remains unclear. Methods:We enrolled 125 ICH patients admitted to Fuyang People's Hospital (July 2024-May 2026), split into 28-day survivors (n = 77) and non-survivors (n = 48). Admission serum CRP, ALB and IL-6 were tested. GCS score assessed brain injury severity, and ICH score stratified 28-day death risk. Baseline data were compared between groups. Spearman correlation analyzed links of CAR, IL-6 with GCS and ICH scores. Multivariate logistic regression identified independent predictors; ROC curve analysis was performed to evaluate the predictive performance of CAR, IL-6, and their combined model. Results:Serum CAR and IL-6 were markedly higher in 28-day non-survivors and rose progressively with aggravated brain injury and higher ICH mortality risk. The two biomarkers showed moderate negative correlations with GCS scores and weak positive correlations with ICH scores (all p < 0.05). Age, ICH score, GCS, CAR and IL-6 were significant in univariate regression. Separate multivariate logistic regression models adjusted for age, hematoma volume and admission GCS score showed that CAR (OR = 1.540, 95% CI: 1.092-2.172, p = 0.014) and IL-6 (OR = 3.940, 95% CI: 1.034-15.003, p = 0.044) independently predicted 28-day mortality. The combined CAR-IL-6 model yielded a raw AUC of 0.810, with individual AUC values of 0.702 for CAR and 0.718 for IL-6. DeLong's test revealed it performed significantly better than CAR alone (p = 0.035), and the model achieved a maximum Youden index of 0.558. Conclusion:Serum CAR and IL-6 independently correlate with brain injury severity and 28-day mortality after ICH, acting as easily accessible predictive biomarkers. Prospective research is necessary to verify their clinical utility for early risk stratification.
Introduction:Patients with critical illness experience profound circadian disruption, driven in part by atypical light exposure in the intensive care unit (ICU). While prior studies characterize ICU light, the extent to which in patient, temporal, and structural factors determine light intensity remains unclear. Methods:We conducted an observational cohort study of light intensity in the rooms of patients admitted to one of thirteen medical ICU (MICU) rooms equipped with continuous light monitoring between February 2021 and 2022. Patients were included if they remained in the monitored MICU room for at least 48 h. We collected patient demographics and clinical features. We recorded light intensity (lux) every 60 s, and then calculated hourly mean lux, hourly proportion of measures ≥250 lux, and hourly proportion of measures ≤10 lux for the first 48 h of each patient's MICU admission. Intraclass correlation coefficients (ICC) quantified variance in each light outcome attributable to patient-level factors. Multivariable multilevel models assessed adjusted associations between patient, temporal and structural factors and light outcomes. Both ICCs and multilevel models were generated separately for day (05:00-22:59) and night (23:00-04:59). Results:Among the 337 patient-room pairs, the mean (± standard deviation) age of patients was 66.1 ± 14.8 years; mean SOFA score was 6.8 ± 3.6; and daytime and nighttime mean lux were 173.8 ± 94.6 and 63.7 ± 88.2, respectively. ICCs indicated that patient-level factors explained 26.3% of daytime and 46.9% of nighttime variance in mean lux; ICC results were similar for other light outcomes. In multivariate models we found that temporal (e.g., time of day, season of ICU admission) and structural factors (e.g., room direction) strongly influenced daytime light levels, whereas nighttime variation was more heavily driven by patient-level factors such as mechanical ventilation status. Conclusion:ICU light exposure shows substantial between-patient variability, particularly at night. In multilevel models, we found that this variability is driven by clinical, temporal and structural factors. Our findings suggest that structural design alone is insufficient to normalize ICU light exposure, and that interventions targeting nocturnal care behaviors and daytime light provision may be necessary to mitigate circadian disruption in patients with critical illness.
Background:Post-stroke dysphagia is common and is associated with aspiration pneumonia, malnutrition, longer hospitalization, and reduced quality of life. Trials evaluating interventions for post-stroke dysphagia face persistent challenges in selecting endpoints that are both patient-centered and methodologically robust. Objectives:To derive and justify a patient-reported outcome (PRO) endpoint for stroke-related dysphagia that supports clinically meaningful interpretation, statistical efficiency, and alignment with regulatory expectations. Methods:We synthesized regulatory guidance, outcomes-research standards, and stroke-specific evidence to develop a dichotomous, status-based PRO responder endpoint at 90 days post-stroke that integrates swallowing-specific quality of life (SWAL-QOL) and global health-related quality of life (EuroQol-5D; EQ-5D). Responder definitions were calibrated to baseline dysphagia severity using swallowing-relevant National Institutes of Health Stroke Scale (NIHSS) subcomponents assessed in the early post-acute period. Monte Carlo simulations (10,000 simulated patients with post-stroke dysphagia) compared performance of the combined responder endpoint versus (i) continuous SWAL-QOL and (ii) utility-weighted modified Rankin Scale (UW-mRS) analyses under clinically realistic severity distributions and treatment effects. Sample size requirements were estimated for individually randomized and stepped-wedge designs. Results:Severity-anchored responder endpoints were more statistically efficient and more interpretable than continuous or change-based analyses in heterogeneous acute stroke populations. In simulation, combined SWAL-QOL + EQ-5D responder rates increased from 42.7% (control) to 66.2% (treatment), an absolute difference of 23.5% (odds ratio 2.58, 95% CI 2.38-2.81; number needed to treat ≈ 4-5), with the largest effects in moderate and severe dysphagia. In contrast, mean SWAL-QOL improved by 8.3 points (near or below commonly cited minimal clinically important difference thresholds), and mean UW-mRS improved by 0.017, indicating limited sensitivity of global disability measures. Conclusion:A severity-calibrated, dichotomous PRO responder endpoint combining SWAL-QOL and EQ-5D provides a patient-centered, statistically efficient, and methodologically robust framework for evaluating therapeutic interventions in post-stroke dysphagia.
