Forecasting and mapping dengue fever epidemics in China: a spatiotemporal analysis.

BACKGROUND: Dengue fever (DF) has emerged as a significant public health concern in China. The spatiotemporal patterns and underlying influencing its spread, however, remain elusive. This study aims to identify the factors driving these variations and to assess the city-level risk of DF epidemics in China. METHODS: We analyzed the frequency, intensity, and distribution of DF cases in China from 2003 to 2022 and evaluated 11 natural and socioeconomic factors as potential drivers. Using the random forest (RF) model, we assessed the contributions of these factors to local DF epidemics and predicted the corresponding city-level risk. RESULTS: Between 2003 and 2022, there was a notable correlation between local and imported DF epidemics in case numbers (r = 0.41, P < 0.01) and affected cities (r = 0.79, P < 0.01). With the increase in the frequency and intensity of imported epidemics, local epidemics have become more severe. Their occurrence has increased from five to eight months per year, with case numbers spanning from 14 to 6641 per month. The spatial distribution of city-level DF epidemics aligns with the geographical divisions defined by the Huhuanyong Line (Hu Line) and Qin Mountain-Huai River Line (Q-H Line) and matched well with the city-level time windows for either mosquito vector activity (83.59%) or DF transmission (95.74%). The RF models achieved a high performance (AUC = 0.92) when considering the time windows. Importantly, they identified imported cases as the primary influencing factor, contributing significantly (24.82%) to local DF epidemics at the city level in the eastern region of the Hu Line (E-H region). Moreover, imported cases were found to have a linear promoting impact on local epidemics, while five climatic and six socioeconomic factors exhibited nonlinear effects (promoting or inhibiting) with varying inflection values. Additionally, this model demonstrated outstanding accuracy (hitting ratio = 95.56%) in predicting the city-level risks of local epidemics in China. CONCLUSIONS: China is experiencing an increasing occurrence of sporadic local DF epidemics driven by an unavoidably higher frequency and intensity of imported DF epidemics. This research offers valuable insights for health authorities to strengthen their intervention capabilities against this disease.

Individualized time windows enhance TMS-EEG signal characterization and improve assessment of cortical function in schizophrenia.

Transcranial magnetic stimulation and electroencephalography (TMS-EEG) recordings are crucial to directly assess cortical excitability and inhibition in a non-invasive and task-free manner. TMS-EEG signals are characterized by TMS-evoked potentials (TEPs), which are employed to evaluate cortical function. Nonetheless, different time windows (TW) have been used to compute them over the years. Moreover, these TWs tend to be the same for all participants omitting the intersubject variability. Therefore, the objective of this study is to assess the effect of using different TWs to compute the TEPs, moving from a common fixed TW to more adaptive individualized TWs. Twenty-nine healthy (HC) controls and twenty schizophrenia patients (SCZ) underwent single-pulse (SP) TMS-EEG protocol. Firstly, only the HC were considered to evaluate the TEPs for three different TWs in terms of amplitude and topographical distribution. Secondly, the SCZ patients were included to determine which TW is better to characterize the brain alterations of SCZ. The results indicate that a more individualized TW provides a better characterization of the SP TMS-EEG signals, although all of them show the same tendency. Regarding the comparison between groups, the individualized TW is the one that provides a better differentiation between populations. They also provide further support to the possible imbalance of cortical excitability/inhibition in the SCZ population due to its reduced activity in the N45 TEP and greater amplitude values in the N100. Results also suggest that the SCZ brain has a baseline hyperactive state since the TEPs of the SCZ appear earlier than those of the HC.

Evolving brain network dynamics in early childhood: Insights from modular graph metrics.

Modular dynamic graph theory metrics effectively capture the patterns of dynamic information interaction during human brain development. While existing research has employed modular algorithms to examine the overall impact of dynamic changes in community structure throughout development, there is a notable gap in understanding the cross-community dynamic changes within different functional networks during early childhood and their potential contributions to the efficiency of brain information transmission. This study seeks to address this gap by tracing the trajectories of cross-community structural changes within early childhood functional networks and modeling their contributions to information transmission efficiency. We analyzed 194 functional imaging scans from 83 children aged 2 to 8 years, who participated in passive viewing functional magnetic resonance imaging sessions. Utilizing sliding windows and modular algorithms, we evaluated three spatiotemporal metrics-temporal flexibility, spatiotemporal diversity, and within-community spatiotemporal diversity-and four centrality metrics: within-community degree centrality, eigenvector centrality, between-community degree centrality, and between-community eigenvector centrality. Mixed-effects linear models revealed significant age-related increases in the temporal flexibility of the default mode network (DMN), executive control network (ECN), and salience network (SN), indicating frequent adjustments in community structure within these networks during early childhood. Additionally, the spatiotemporal diversity of the SN also displayed significant age-related increases, highlighting its broad pattern of cross-community dynamic interactions. Conversely, within-community spatiotemporal diversity in the language network exhibited significant age-related decreases, reflecting the network's gradual functional specialization. Furthermore, our findings indicated significant age-related increases in between-community degree centrality across the DMN, ECN, SN, language network, and dorsal attention network, while between-community eigenvector centrality also increased significantly for the DMN, ECN, and SN. However, within-community eigenvector centrality remained stable across all functional networks during early childhood. These results suggest that while centrality of cross-community interactions in early childhood functional networks increases, centrality within communities remains stable. Finally, mediation analysis was conducted to explore the relationships between age, brain dynamic graph metrics, and both global and local efficiency based on community structure. The results indicated that the dynamic graph metrics of the SN primarily mediated the relationship between age and the decrease in global efficiency, while those of the DMN, language network, ECN, dorsal attention network, and SN primarily mediated the relationship between age and the increase in local efficiency. This pattern suggests a developmental trajectory in early childhood from global information integration to local information segregation, with the SN playing a pivotal role in this transformation. This study provides novel insights into the mechanisms by which early childhood brain functional development impacts information transmission efficiency through cross-community adjustments in functional networks.

An auto-segmented multi-time window dual-scale neural network for brain-computer interfaces based on event-related potentials.

Objective.Event-related potentials (ERPs) are cerebral responses to cognitive processes, also referred to as cognitive potentials. Accurately decoding ERPs can help to advance research on brain-computer interfaces (BCIs). The spatial pattern of ERP varies with time. In recent years, convolutional neural networks (CNNs) have shown promising results in electroencephalography (EEG) classification, specifically for ERP-based BCIs.Approach.This study proposes an auto-segmented multi-time window dual-scale neural network (AWDSNet). The combination of a multi-window design and a lightweight base network gives AWDSNet good performance at an acceptable cost of computing. For each individual, we create a time window set by calculating the correlation of signedR-squared values, which enables us to determine the length and number of windows automatically. The signal data are segmented based on the obtained window sets in sub-plus-global mode. Then, the multi-window data are fed into a dual-scale CNN model, where the sizes of the convolution kernels are determined by the window sizes. The use of dual-scale spatiotemporal convolution focuses on feature details while also having a large enough receptive length, and the grouping parallelism undermines the increase in the number of parameters that come with dual scaling.Main results.We evaluated the performance of AWDSNet on a public dataset and a self-collected dataset. A comparison was made with four popular methods including EEGNet, DeepConvNet, EEG-Inception, and PPNN. The experimental results show that AWDSNet has excellent classification performance with acceptable computational complexity.Significance.These results indicate that AWDSNet has great potential for applications in ERP decoding.

The time window for pre-emptive transjugular intrahepatic portosystemic shunt could be extended to 5 days.

As recommended by Baveno VII consensus, the utilization of pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) has been considered as standard therapeutic approach for the management of acute variceal bleeding (AVB) associated with cirrhosis., but the 72-h window for pTIPS is too narrow. This study aimed to compare the clinical outcomes between patients who received <72 h pTIPS and 72 h-5d pTIPS. In this study, a total of 63 cirrhotic patients with AVB who underwent pTIPS between October 2016 and December 2021 were included in this retrospective study. They were divided into <72 h group (n = 32) and 72 h-5d group (n = 31), based on the timing of the intervention. The Kaplan-Meier curves demonstrated that there were no significant differences in the cumulative incidence of death (22.3% ± 7.4% vs. 19.9% ± 7.3%, log-rank P = 0.849), variceal rebleeding (9.7% ± 5.3% vs. 17.8% ± 7.3%, log-rank P = 0.406), OHE (28.5% ± 8.0% vs. 23.9% ± 8.0%, log-rank P = 0.641) and shunt dysfunction (8.6% ± 6.0% vs. 17.4% ± 8.1%, log-rank P = 0.328) between <72 h and 72 h-5d groups. In the total cohort, sarcopenia was identified as an independent risk factor for mortality (HR = 11.268, 95% CI = 1.435-88.462, P = 0.021) and OHE(HR = 12.504, 95% CI = 1.598-97.814, P = 0.016). In conclusion, the clinical outcomes of cirrhotic patients with AVB who underwent pTIPS within the 72-h to 5-day window were found to be comparable to those treated within the 72-h window.

Infrared thermography reveals weathering hotspots at the Pozáry field laboratory.

Evaluating physical properties and mechanical parameters of rock slopes and their spatial variability is challenging, particularly at locations inaccessible for fieldwork. This obstacle can be bypassed by acquiring spatially-distributed field data indirectly. InfraRed Thermography (IRT) has emerged as a promising technology to statistically infer rock properties and inform slope stability models. Here, we explore the use of Cooling Rate Indices (CRIs) to quantify the thermal response of a granodiorite rock wall within the recently established Pozáry Test Site in Czechia. We observe distinct cooling patterns across different segments of the wall, compatible with the different degrees of weathering evaluated in the laboratory and suggested by IRT observations of cored samples. Our findings support previous examinations of the efficacy of this method and unveil correlations between cooling phases in the field and in the laboratory. We discuss the scale-dependency of the Informative Time Window (ITW) of the CRIs, noting that it may serve as a reference for conducting systematic IRT field surveys. We contend that our approach not only represents a viable and scientifically robust strategy for characterising rock slopes but also holds the potential for identifying unstable areas.

Comparison of functional and safety outcomes between the extended versus early time window after intravenous thrombolysis and endovascular thrombectomy.

INTRODUCTION: Based on recent trials regarding the early time window, omitting intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in eligible patients seems unjustified. Whether this also concerns the extended time window, 4.5 to 9 h from last seen well, is yet unclear. PATIENTS AND METHODS: All consecutive patients treated with IVT, EVT, or IVT plus EVT in the extended time window at Helsinki University Hospital (HUS) between 1/2021 and 12/2022 were compared with matched controls treated in the early time window between 1/2016 and 12/2020. Regression analysis was applied on functional outcome at 90 days, evaluated on modified Rankin Scale (mRS), and on the occurrence of symptomatic intracerebral hemorrhage (sICH), adjusted for potential confounders. RESULTS: Altogether 134 patients and 134 matching controls were included. Functional outcomes did not significantly differ between the extended versus early time window. Among patients with IVT plus EVT, the adjusted odds ratio (aOR) for a favorable outcome shift on mRS was 1.15, 95% confidence interval (CI) 0.54-2.43. Although sICH occurred more frequently (2.2% versus 3.0%) in the extended time window, regression analysis did not show a significant difference, aOR 0.96, 95% CI 0.14-6.87. DISCUSSION AND CONCLUSION: We found no significant differences in the functional or safety outcomes between the extended versus early time window among patients with either IVT, EVT, or IVT plus EVT. There were no signals indicating, that IVT or EVT should be avoided in eligible patients in the extended time window which aligns with the current clinical treatment guidelines of HUS.

Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke.

INTRODUCTION: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. PATIENTS AND METHODS: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. RESULTS: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). CONCLUSION: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; Unique identifier: NCT04096248.

Eating Frequency, Timing, and Duration in Relation to Cognitive Performance and Alzheimer Disease Biomarkers in Adults.

BACKGROUND: The potential association between temporal dimensions of eating and cognition/cognitive declines has been poorly investigated so far. OBJECTIVES: The aim of this study was to examine relationships among eating frequency, timing and time window, and cognitive performance and novel Alzheimer disease (AD) biomarkers in cognitively healthy and mildly cognitively impaired middle-aged and older adults. METHODS: Cross-sectional data were derived from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) cohort study, including people aged 40 y or older who have a positive family history of cognitive disorder or cognition-related concerns. Cognitive performance was assessed by a battery of neuropsychological tests. Amyloid ß (Αß42), a biomarker of AD-related pathology, was measured in cerebrospinal fluid. Eating frequency, timing, and the eating time window between the first and the last meal were estimated using time-related information recorded in four 24-h recalls. RESULTS: Study participants had, on average, 5.3 ± 1.2 eating episodes per day, consumed at 8:20 ± 1.3 and 21:14 ± 1.3 h their first and their last eating episode, respectively, while their eating time window was 12.9 ± 1.6 h. Eating frequency, but not eating time window, was positively associated with global cognition, executive and language performance even after controlling for age, sex, education, BMI, and Mediterranean diet. Increasing eating frequency by 1 eating episode per day was associated with 0.169 higher global z-score. Furthermore, compared with ≤4, having 5-6 or >6 eating episodes per day was associated with better global and memory z-scores. Time of last eating episode was also positively associated with language performance. No associations were detected among eating frequency, timing and window, and AD pathology. CONCLUSIONS: An eating pattern characterized by less frequent eating and/or by earlier times is present in individuals with worse cognitive performance. Our results shed light on the relevance of temporal eating patterns as potential early markers of behavioral or metabolic changes related to AD pathology.

Endovascular treatment of stroke in the late time window with large vessel occlusion using the ASPECTS as an imaging screening criterion.

To assess the Alberta Stroke Program Early CT Score (ASPECTS) screening tool for effectiveness in endovascular treatment of late time window stroke with large vessel occlusion. A retrospective analysis was performed of individuals administered endovascular treatment in our neurology department between 2016 and 2020 for ischemic stroke induced by acute large vessel occlusion in the anterior circulation and ASPECTS ≥ 6. Detailed baseline and endovascular treatment data were collected. Patients were assigned to 2 groups based on stroke onset time, including the 0-6 h (treated within 6 h of stroke onset) and 6-24 h (earlier/unknown time of onset, up to 24 h from the last time of appearing normal) groups. Both groups were compared for baseline information, revascularization rates, symptomatic intracranial hemorrhage, and 90-day functional independence. Totally 221 individuals were enrolled. The 0-6 h and 6-24 h groups had 129 and 92 patients, respectively, whose median ages were 64 and 63 years, respectively. Both groups were similar in previous medical history, NIHSS score at onset, lesion location and surgical complications. The 6-24 h group had elevated intracranial atherosclerotic stenosis (48.9 vs. 33.3%, P = 0.020) and revascularization (96.7 vs. 86.8%, P = 0.011) rates versus the 6-24 h group. Upon adjustment for age, sex, National Institutes of Health Stroke Scale, ASPECTS, Intracranial atherosclerosis, intraoperative tirofiban, stent detachment, successful recanalization, and symptomatic intracranial hemorrhage, the 0-6 h group had a higher rate of individuals achieving functional independence (mRS score of 0-2; 52.7 vs. 47.8%, OR = 0.242 [0.070-0.833], P = 0.024). However, the rates of individuals with a favorable outcome (mRS scores of 0-3) were similar in both groups (66.7 vs. 69.6%; OR = 0.564 [0.140-2.266], P = 0.419) as well as 90-d mortality (OR = 0.889 [0.170-4.660], P = 0.889). The ASPECTS is effective for screening individuals for endovascular treatment of stroke in the late time window with large vessel occlusion. The ASPECTS should be considered a simple and practical patient screening strategy for stroke centers without multimodal imaging evaluation.

A visceral organ function-focused therapeutic strategy using a 6-hour time window for patients with acute type a aortic dissection complicated by mesenteric malperfusion.

BACKGROUND: Acute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion. METHODS: This was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h. RESULTS: There were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences. CONCLUSIONS: Our novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate.

Impacts of futile reperfusion and reperfusion injury in acute ischemic stroke.

Acute ischemic stroke (AIS) remains to be a challenging cerebrovascular disease. The mainstay of AIS management is endovascular reperfusion therapy, including thrombectomy and thrombolysis. However, ineffective (futile) reperfusion (FR) or reperfusion injury (RI) can be seen in a significant number of patients undergoing reperfusion strategy. In this article, we discuss two clinically relevant concepts known as "time window" and "tissue window" that can impact the clinical outcome of reperfusion therapy. We also explore patient risk factors, leading to FR and RI as well as an emerging concept of "no-reflow phenomenon" seen in ineffective reperfusion. These fundamental concepts provide insight into the clinical management of AIS patients and provide references for future research.

The temporal transition zone: A gradual approach to a subjective set-point within the three-second time window.

Even though in physics "time" is considered to be continuous, how the brain and mind deal with time might be different. It has been proposed that in cognition, time windows provide logistic platforms for information processing, such as the low-frequency 3-s time window. The following series of behavioral experiments may shed light on the dynamics within such a time window. Using a duration reproduction paradigm, we first replicated a pattern of reproduced duration observed in a previous single-case study. Specifically, the reproduction increases as the pause between standard duration and reproduction increases, but only within the time window of some 3 s; when the pause goes beyond 4 s, the reproduction reaches a plateau of a subjective set-point. This increasing phase is named the "temporal transition zone." Three more experiments were performed to test the features of the transition zone as a low-frequency time window. It is also observed with different standard durations (2, 3, 4.5 s, in Experiment 2), and even when the frequency of the auditory stimuli was different in standard and reproduction (300 Hz in standard duration and 400 Hz in reproduction, in Experiment 4). The transition zone was observed only with pause durations of 2 to 3 s; when the shortest pause duration was 5 s, the transition zone was no longer observed, and the reproduction was stable at the subjective set-point (in Experiment 3). Taken together, we suggest that the temporal transition zone indicates a pre-semantic logistic platform to organize and process the information flow; in such a time window of some 3 seconds, the identity of an ongoing event is substantiated, building the "subjective present."

Addressing bias in the definition of SARS-CoV-2 reinfection: implications for underestimation.

Introduction: Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection. Methods: A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed. Results: The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results. Discussion: A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic.

Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury.

PURPOSE: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. METHODS: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q1, Q3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. RESULTS: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 - 25.42, p = 0.002), 2.85 (95% CI: 1.11 - 7.31, p = 0.030), 2.62 (95% CI: 1.12 - 6.13, p = 0.027), 2.44 (95% CI: 1.25 - 4.76, p = 0.009), and 1.5 (95% CI: 1.10 - 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. CONCLUSION: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1ß pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

Clinical activity in general practice before sarcoma diagnosis: an Australian cohort study.

BACKGROUND: Increased time to diagnosis in sarcoma is associated with poor prognosis and patient outcomes. Research is needed to identify whether opportunities to expedite the diagnosis of sarcoma in general practice exist. AIM: To examine pre-diagnostic GP clinical activity before sarcoma diagnosis. DESIGN AND SETTING: An Australian retrospective cohort study using hospital registry data (Australian Comprehensive Cancer Outcomes and Research Database [ACCORD]) linked to two primary care datasets (Patron and MedicineInsight). METHOD: The frequency of general practice healthcare utilisation events (general practice attendances, prescriptions, blood test, and imaging requests) were compared in 377 patients with soft tissue sarcoma (STS) and 64 patients with bone sarcoma (BS) in the year pre-diagnosis. Poisson regression models were used to calculate monthly incidence rate ratios (IRR) for the 24 months pre-diagnosis and estimate inflection points for when healthcare use started to increase from baseline. RESULTS: In the 6 months pre-diagnosis, patients with sarcoma had a median of 3-4 general practice attendances, around one-third had a GP imaging request (33% [n = 21] BS and 36% [n = 134] STS), and approximately one in five had multiple imaging requests (19% [n = 12] BS and 21% [n = 80] STS). GP imaging requests progressively increased up to eight-fold from 6 months before sarcoma diagnosis (IRR 8.43, 95% confidence interval [CI] = 3.92 to 18.15, P<0.001) and general practice attendances increased from 3 months pre-diagnosis. CONCLUSION: Patients with sarcoma have increased GP clinical activity from 6 months pre-diagnosis, indicating a diagnostic window where potential opportunities exist for earlier diagnosis. Interventions to help identify patients and promote appropriate use of imaging and direct specialist centre referrals could improve earlier diagnosis and patient outcomes.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Optimal time window for initiating cefuroxime surgical antimicrobial prophylaxis in spinal fusion surgery: a nested case-control study.

BACKGROUND CONTEXT: Surgical site infections (SSI) are one of the common complications following spinal fusion surgery. Unfortunately, several studies had shown conflicting results regarding optimal timing of surgical antimicrobial prophylaxis (SAP) administration. Due to limitations in population homogeneity and sample size, these studies have not provided significant statistical correlations or clear practical recommendations. PURPOSE: The purpose of the study was to investigate the impact of timing of cefuroxime SAP on the risk of SSI in patients undergoing spinal fusion surgery, and to determine the optimal timing of administration. DESIGN: Retrospective nested case-control study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021. OUTCOME MEASURE: In the current study, the primary outcome measure was SSI. METHODS: This was a retrospective nested case-control study. All consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021 formed a retrospective cohort. For each SSI case, 2 controls free of SSI at the time of the index date of their corresponding case were selected, matched by age, sex, and calendar year. Electronic record and radiographic data were reviewed retrospectively in electronic database. SAP related data included timing of administration, preoperative dose, intraoperative second dose, and postoperative use. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Subsequently, subgroup analyses were conducted to assess the robustness of the statistical associations. RESULTS: According to the preplanned statistical scheme and matching factors, we matched 236 controls for these SSI cases, and the subsequent statistical analysis was performed on these 354 patients. After adjusting for confounding factors, the results indicated that the risk of SSI was 70% higher in the group receiving SAP 31 to 60 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=1.732, 95%CI 1.031-2.910, p=.038). Additionally, the risk of SSI was 150% higher in the group receiving SAP 61 to 120 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=2.532, 95%CI 1.250-5.128, p=.010). In subgroup analysis, this statistical trend persisted for both deformity surgeries and different SSI classifications. CONCLUSION: Administering cefuroxime SAP within 30 minutes before skin incision significantly reduces the risk of SSI, whether they are deep or superficial, in spinal fusion surgery. This pattern remains consistent among spinal deformity patients.

Early and late basilar artery thrombectomy time window outcomes.

Importance: Stroke-to-recanalization time is a strong predictor of outcomes in anterior circulation large-vessel occlusion (LVO). The authors aimed to evaluate functional outcomes in early (<6 h) vs. late (6-24 h) time windows for thrombectomy-treated basilar artery occlusions. Methods: Patients were derived from the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-procedural Predictors of Mechanical Thrombectomy (PC-SEARCH) Registry and retrospectively analyzed early and late basilar artery thrombectomy time windows cohorts. Patients were dichotomized based on the last known well and correlated to 90-day functional outcomes (mRS 0-3). A multiple logistic regression analysis was performed. Results: A total of 405 patients were included in this study: 216 and 189 patients in the early and late time windows, respectively. Baseline demographic, stroke, radiographic, and intraprocedural characteristics were similar between the groups. A total of 99 (46%) and 79 (42%) patients in the early and late time windows, respectively, achieved favorable functional outcomes at 90 days (p = 0.41), and multiple logistic regression analysis did not reveal differences between cohorts (OR: 0.74; 95% CI: 0.46-1.19; p = 0.22). Symptomatic hemorrhage (7% vs. 5%; p = 0.69) and neurological complications (8% vs. 9%; p = 0.83) were similar between the groups; however, hospital complications were more common in the early time window cohort (22% vs. 13%; p = 0.01). Conclusion: The early and late thrombectomy time windows can achieve similar rates of 90-day favorable functional outcomes. However, timely thrombectomy influences the likelihood of achieving excellent functional outcomes (mRS ≤ 2) within the early time window.