Trajectories of health-related quality of life following road trauma: Latent growth mixture modeling across a 12-month cohort study.

INTRODUCTION: Health-related quality of life (HRQoL) should be considered when evaluating the burden of road trauma (RT) injuries. This study aimed to identify distinct HRQoL trajectories following minor to severe RT injury and determine characteristics of trajectory membership. METHODS: This prospective inception cohort study recruited 1480 RT survivors from three emergency departments in British Columbia, Canada (July 2018 - March 2020). HRQoL outcome was measured with the Short Form 12 survey (SF-12) and the 5-level version of the EuroQol instrument (EQ-5D-5L) at baseline (pre-injury) and at 2, 4, 6, and 12 months post-injury. Potential predictors of outcome trajectory included sociodemographic, psychological, medical, crash, and injury factors collected at baseline. We used a latent growth mixture model to identify distinct recovery trajectories and multinomial logistic regression to determine predictors of trajectory membership. RESULTS: Three distinct HRQoL trajectories were identified for SF-12 subscales and EQ-5D-5L measures: Low/Moderate-Stable, High-Large decline, and High-Slight decline. Participants in the Low/Moderate-Stable trajectory had persistent low to moderate HRQoL before and after the injury. Those in the High-Large decline trajectory had good pre-injury HRQoL followed by persistently decreased HRQoL afterwards. The High-Slight decline trajectory was characterized by good pre-injury HRQoL and only a slight decline afterwards. Participants in the Low/Moderate-Stable and High-Large decline trajectories were considered at risk of permanently poor HRQoL following RT injury given their low HRQoL over a long period of time. Characteristics that placed participants in the Low/Moderate-Stable trajectory were older age, female gender, poor pre-injury health (medical comorbidity, prescribed medication use, complaints in the injured body area(s)), pre-injury somatic symptoms, pain catastrophizing or psychological distress, injury severity (ISS) and injury pain. Patients with head injury were less likely to be in the Low/Moderate-Stable trajectory. Risk factors for membership in the High-Large decline trajectory included older age (for physical HRQoL), younger age (for mental HRQoL), female gender, living alone, pre-injury psychological distress, ISS, injury pain, no expectations for a fast recovery, as well as head injuries, spine/back injuries or lower extremity injuries. CONCLUSIONS: This study highlighted the heterogeneity of HRQoL trajectories following RT injury and the importance of considering differences between characteristics of survivors. In addition to injury type and severity, outcome is related to demographic factors, pre-injury health and pre-injury psychological factors.

Screening for harmful substance use in emergency departments: a systematic review.

BACKGROUND: Substance use-related emergency department (ED) visits have increased substantially in North America. Screening for substance use in EDs is recommended; best approaches are unclear. This systematic review synthesizes evidence on diagnostic accuracy of ED screening tools to detect harmful substance use. METHODS: We included derivation or validation studies, with or without comparator, that included adult (≥ 18 years) ED patients and evaluated screening tools to identify general or specific substance use disorders or harmful use. Our search strategy combined concepts Emergency Department AND Screening AND Substance Use. Trained reviewers assessed title/abstracts and full-text articles for inclusion, extracted data, and assessed risk of bias (QUADAS-2) independently and in duplicate. Reviewers resolved disagreements by discussion. Primary investigators adjudicated if necessary. Heterogeneity precluded meta-analysis. We descriptively summarized results. RESULTS: Our search strategy yielded 2696 studies; we included 33. Twenty-one (64%) evaluated a North American population. Fourteen (42%) applied screening among general ED patients. Screening tools were administered by research staff (n = 21), self-administered by patients (n = 10), or non-research healthcare providers (n = 1). Most studies evaluated alcohol use screens (n = 26), most commonly the Alcohol Use Disorders Identification Test (AUDIT; n = 14), Cut down/Annoyed/Guilty/Eye-opener (CAGE; n = 13), and Rapid Alcohol Problems Screen (RAPS/RAPS4/RAPS4-QF; n = 12). Four studies assessing six tools and screening thresholds for alcohol abuse/dependence in North American patients (AUDIT ≥ 8; CAGE ≥ 2; Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-2] ≥ 1; RAPS ≥ 1; National Institute on Alcohol Abuse and Alcoholism [NIAAA]; Tolerance/Worry/Eye-opener/Amnesia/K-Cut down [TWEAK] ≥ 3) reported both sensitivities and specificities ≥ 83%. Two studies evaluating a single alcohol screening question (SASQ) (When was the last time you had more than X drinks in 1 day?, X = 4 for women; X = 5 for men) reported sensitivities 82-85% and specificities 70-77%. Five evaluated screening tools for general substance abuse/dependence (Relax/Alone/Friends/Family/Trouble [RAFFT] ≥ 3, Drug Abuse Screening Test [DAST] ≥ 4, single drug screening question, Alcohol, Smoking and Substance Involvement Screening Test [ASSIST] ≥ 42/18), reporting sensitivities 64%-90% and specificities 61%-100%. Studies' risk of bias were mostly high or uncertain. CONCLUSIONS: Six screening tools demonstrated both sensitivities and specificities ≥ 83% for detecting alcohol abuse/dependence in EDs. Tools with the highest sensitivities (AUDIT ≥ 8; RAPS ≥ 1) and that prioritize simplicity and efficiency (SASQ) should be prioritized.

Atrial Cardiomyopathy Predicts the Functional Outcome and Mortality in Stroke Patients.

AIM: Atrial cardiomyopathy (ACM) is characterized by atrial dysfunction. This study aims to assess the prognostic significance of ACM in patients with noncardioembolic stroke (NCS). METHODS: Patients with NCS within seven days of onset were prospectively enrolled between January 2019 and December 2020. ACM was defined as either an N-terminal pro-brain natriuretic peptide (NT-pro BNP) ＞250 pg/ml or a P-terminal force in precordial lead V1 (PTFV1) ≥ 5000µV·ms. A poor functional outcome was determined as a score of 3-6 on the modified Rankin Scale (mRS) within a 2-year follow-up period. Logistic regression and Cox regression analyses were employed to examine the relationship between ACM and the long-term prognosis of patients with NCS. RESULTS: A total of 1,346 patients were enrolled, of whom 299 (22.2%) patients were diagnosed with ACM. A total of 207(15.4%) patients experienced a poor functional outcome, and 58 (4.3%) patients died. A multivariate logistic regression analysis indicated that ACM was significantly associated with a poor functional outcome in NCS patients [adjusted odds ratio (aOR): 2.01; 95% confidence interval (CI): 1.42-2.87; p＜0.001]. Additionally, a multivariate Cox regression analysis showed that an NT-pro BNP ＞250 pg/ml was significantly associated with an increased risk of all-cause mortality [adjusted hazard ratio (aHR), 2.51; 95% CI: 1.42-4.43; p=0.001]. CONCLUSIONS: ACM may serve as a novel predictor of a poor long-term functional outcome in patients with NCS. Elevated NT-pro BNP levels (＞250 pg/ml) were found to be associated with a higher risk of all-cause mortality. These findings warrant further validation in multicenter studies.

Twelve-month recovery following road trauma: Results from an inception cohort in Vancouver, Canada.

BACKGROUND: Injury-related disability following road trauma is a major public health concern. Unfortunately, outcome following road trauma and risk factors for poor recovery are inadequately studied, especially for road trauma survivors with minor injuries that do not require hospitalization. OBJECTIVES: This manuscript reports 12-month recovery outcomes for a large cohort of road trauma survivors. METHODS: This was a prospective, observational inception cohort study of 1,480 road trauma survivors recruited between July 2018 and March 2020 from 3 trauma centres in British Columbia, Canada. Participants were aged ≥16 years and arrived in a participating emergency department within 24 h of a motor vehicle collision. Data on baseline health and injury severity were collected from structured interviews and medical records. Outcome measures, including the SF-12, were collected during follow-up interviews at 2, 4, 6 and 12 months. Predictors of recovery outcomes were identified using Cox proportional hazards models and summarized using hazard ratios. RESULTS: Only 42 % of participants self-reported full recovery and only 66 % reported a return to usual daily activities. Females, older individuals, pedestrians, and those who required hospital admission had a poorer recovery than other groups. Similar patterns were observed for the SF-12 physical component. For the SF-12 mental component, no significant differences were observed between participants admitted to hospital and those discharged home from the ED. Return to work was reported by 77 % of participants who had a paying job at baseline, with no significant differences between sex and age groups. CONCLUSIONS: In a large cohort of road trauma survivors, under half self-reported full recovery one year after the injury. Poor mental health recovery was observed in both participants admitted to hospital and those discharged home from the ED. This finding may indicate a need for early intervention and continued mental health monitoring for all injured individuals, including for those with less serious injuries.

Health-related quality of life in the year following road trauma: Longitudinal analysis using piecewise latent curve modeling.

BACKGROUND: Road trauma (RT) survivors have reduced health-related quality of life (HRQoL). We identified phases and predictors of HRQoL change following RT injury. METHODS: In a prospective cohort study of 1480 Canadian RT survivors aged 16 to 103 years (July 2018 - March 2020), physical component (PCS) and mental component (MCS) summary scores from the SF-12v2 were measured pre-injury and 2, 4, 6, and 12 months post-injury and their trajectories were analyzed with piecewise latent growth curve modeling. Potential predictors of HRQoL changes included sociodemographic, psychological, medical, and trauma-related factors. RESULTS: PCS and MCS scores worsened from pre-injury to 2-months (phase 1) and then improved (phase 2), but never regained baseline values. Older age, somatic symptoms and pain catastrophizing were associated with lower preinjury PCS and MCS scores. Psychological distress was associated with lower preinjury MCS scores and higher preinjury PCS scores. Phase 1 PCS scores decreased most in females, participants with fewer pre-injury somatic symptoms and those without expectations for fast recovery. Phase 1 MCS decreases were associated with younger age, female sex, living alone, lower psychological distress, lack of expectation for fast recovery and higher injury pain. In phase 2, MCS improved most in participants not using recreational drugs; PCS improved most in participants with higher education and longer recovery expectations. LIMITATIONS: There may be recall bias with reporting pre-injury HRQoL. Selection bias is possible. CONCLUSIONS: Many factors influence HRQoL following RT. These findings may inform measures to minimize HRQoL reduction following RT and speed up subsequent recovery.

Circumstances and outcome of active transportation injuries: protocol of a British Columbian inception cohort study.

INTRODUCTION: Active transport (AT) is promoted by urban planners and health officials for its environmental, economic and societal benefits and its uptake is increasing. Unfortunately, AT users can be injured or killed due to falls or collisions. Active transport injury (ATI) prevention efforts are hindered by limited research on the circumstances, associated infrastructure, injury pattern, severity and outcome of ATI events. This study seeks to address these knowledge gaps by identifying built environment features associated with injury and risk factors for a poor outcome following ATI. METHODS AND ANALYSIS: This prospective observational study will recruit an inception cohort of 2000 ATI survivors, including pedestrians, cyclists and micromobility users aged 16 years and older who arrive at a participating emergency department within 48 hours of sustaining an ATI. Baseline interviews capture demographic and socioeconomic information, pre-injury health and functional status, as well as circumstances of the injury event and recovery expectations. Follow-up interviews at 2, 4, 6 and 12 months postinjury (key stages of recovery) use standardised health-related quality of life tools to determine physical and mental health outcomes, functional recovery and healthcare resource use and lost productivity costs. ETHICS AND DISSEMINATION: The Active Transportation Injury Circumstances and Outcome Study is approved by our institutional research ethics board and the research ethics boards of all participating sites. This study aims to provide healthcare providers with knowledge of risk factors for poor outcome following ATI with the goal of improving patient management. Additionally, this study will provide insight into the circumstances of ATI events including built environment features and how those circumstances relate to recovery outcomes. This information can be used to inform city engineers and planners, policymakers and public health officials to plan roadway design and injury prevention policy.

ABCD2 score has equivalent stroke risk prediction for anterior circulation TIA and posterior circulation TIA.

Transient ischemic attack (TIA) was clinically divided into anterior circulation (AC) or posterior circulation (PC). Previous study reported that ABCD2 score could predict the stroke risk after AC-TIA but might have limitation for PC-TIA. We aimed to classify TIA depending on neuroimaging and assess the value of ABCD2 score for predicting stroke risk in different territories. Research data was from TIA database of the First Affiliated Hospital of Zhengzhou University. TIA patients with acute infarction on diffuse weighted imaging [that is, transient symptoms with infarction (TSI)] were divided into anterior and posterior circulation groups according to the location of infarction. The outcome was recurrent stroke within 7 and 90 days. The predictive power of ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. Overall, 382 AC-TSI and 112 PC-TSI patients were included. There were 38 (9.9%) AC-TSI patients and 11(9.8%) PC-TSI patients who had recurrent stroke at 7 days, and 66 (17.3%) AC-TSI patients and 19 (17.0%) PC-TSI patients who had recurrent stroke within 90 days. At 7 days, the AUC for ABCD2 score was 0.637 (95% confidence interval CI 0.554-0.720) in anterior circulation and 0.683 (95% CI 0.522-0.845) in posterior circulation. The C statistics for ABCD2 score in the two groups were not statistically significant (Z = - 0.499; P = 0.62). Similar result was found when the outcome time-point was set at 90 days. ABCD2 score could predict the short-term risk of recurrent stroke after AC-TSI and PC-TSI, and had similar predictive abilities for AC-TSI and PC-TSI.

Demographic and clinical profile of an inception cohort of road trauma survivors.

BACKGROUND: Road trauma is a major public health concern, often resulting in reduced health-related quality of life and prolonged absenteeism from work even after so-called 'minor' injuries that do not result in hospitalization. This manuscript compares pre-injury health, sociodemographic characteristics and injury details between age, sex, and road user categories in a cohort of 1,480 road trauma survivors. METHODS: This was a prospective observational inception cohort study of road trauma survivors recruited between July 2018 and March 2020 from three trauma centres in British Columbia, Canada. Participants were aged ≥ 16 years and arrived in a participating emergency department within 24 h of involvement in a motor vehicle collision. Data were collected from structured interviews and review of medical records. RESULTS: The cohort of 1,480 road trauma survivors included 280 pedestrians, 174 cyclists, 118 motorcyclists, 683 motor vehicle drivers, and 225 passengers. Median age was 40 (IQR = [27, 57]) years; 680 (46%) were female. Males and younger patients were significantly more likely to report better pre-injury physical health. Motorcyclists and cyclists tended to report better physical health and less severe somatic symptoms, whereas pedestrians and motor vehicle drivers reported better mental health. Injury severity and hospital admission rates were higher in pedestrians and motorcyclists and lower in motorists. Upper and lower extremity injuries were most common in pedestrians, cyclists and motorcyclists, whereas neck injuries were most common in motor vehicle drivers and passengers. CONCLUSIONS: In a large cohort of road trauma survivors, overall injury severity was low. Motorcyclists and pedestrians, but not cyclists, had more severe injuries than motorists. Extremity injuries were more common in vulnerable road users. Future research will investigate one-year recovery outcomes and identify risk factors for poor recovery.

Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial.

BACKGROUND: Global guidelines recommend untargeted iron supplementation for women in regions of anemia prevalence ≥40%, such as Cambodia. However, the potential harms of untargeted iron on the gut have not been rigorously studied in women and likely vary depending on iron dose and form. OBJECTIVES: We investigated if a lower dose of a highly bioavailable iron amino acid chelate was as effective as the standard dose of iron salts in increasing ferritin concentrations and whether any differences were observed in gut inflammation or enteropathogen detection. METHODS: A double-blind, randomized placebo-controlled noninferiority trial was conducted in Cambodia. Nonpregnant women (n = 480, 18-45 y) were randomly assigned to 60-mg ferrous sulfate, 18-mg ferrous bisglycinate, or placebo for 12 wk. Nonfasting blood and stool specimens were collected at baseline and 12 wk. Ferritin and fecal calprotectin were measured with an ELISA. A molecular assay was used to detect 11 enteropathogens in a random subset of n = 100 women. Generalized linear mixed-effects models were used to estimate the adjusted mean difference in ferritin concentrations at 12 wk (primary outcome), as compared with our 'a priori' noninferiority margin of 20 µg/L. RESULTS: Baseline anemia and iron deficiency prevalence was low (17% and 6%, respectively). The adjusted mean difference in ferritin concentrations between the iron groups was 14.6 (95% confidence interval [CI]: 7.6, 21.6) µg/L. Mean ferritin concentration at 12 wk was higher in the ferrous sulfate (99 [95% CI: 95, 103] µg/L, P < 0.001) than in ferrous bisglycinate (84 [95% CI: 80, 88] µg/L) and placebo groups (78 [95% CI: 74, 82] µg/L). No differences in fecal calprotectin concentrations or enteropathogen detection were observed across groups at 12 wk. CONCLUSIONS: Ferrous bisglycinate (18-mg) was not as effective as ferrous sulfate (60-mg) in increasing ferritin concentrations and did not differentially influence biomarkers of gut health in this predominantly iron-replete population of Cambodian women. This trial was registered at clinicaltrials.gov registry as NCT04017598.

Reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to oral iron supplementation.

AIM: We investigated the potential of reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to iron supplementation. METHODS: Data were obtained from a randomised controlled trial of daily iron supplementation in 356 Cambodian women (18-45 y) who received 60 mg elemental iron for 12 weeks. A fasted venous blood specimen was collected at baseline, 1-week and 12-week timepoints. Whole blood haemoglobin (g/L) and RET-He (pg) were measured using a Sysmex haematology analyser. RET-He measures were evaluated for their predictive ability on haemoglobin response to iron supplementation (defined as ≥10 g/L at 12 weeks). Receiver operating characteristic (ROC) curves were used to assess discrimination performance, and the area under the ROC curve (AUCROC) served as a measure of the ability of each predictor to discriminate between women likely or unlikely to elicit a haemoglobin response. RESULTS: Predictive ability (AUCROC (95% CI)) of baseline, 1-week, and change from baseline to 1-week RET-He on haemoglobin response was 0.70 (0.63 to 0.76), 0.48 (0.41 to 0.56) and 0.81 (0.75 to 0.87), respectively. Based on the Youden index, an absolute increase in RET-He of ~1.1 pg or a percentage increase of ~4.4% over 1 week were optimal thresholds to predict responsiveness to iron supplementation. CONCLUSION: Single timepoint RET-He measures have poor predictive ability; however, change in RET-He after 1 week was a strong predictor of haemoglobin response among Cambodian women receiving 60 mg elemental iron and can be measured easily and quickly after only 1 week of iron therapy.

Neuroimaging markers of early neurological deterioration in acute isolated pontine infarction.

BACKGROUND: Imaging indicators of early neurological deterioration (END) in patients with acute isolated pontine infarctions (AIPI) remained ambiguous. We aimed to find more specific neuroimaging markers for the development of END in patients with AIPI. METHODS: Patients with AIPI within 72 h of stroke onset were screened from a stroke database from January 2018 to July 2021 in the First Affiliated Hospital of Zhengzhou University. Clinical characteristics, laboratory tests, and imaging parameters were collected. The layers having the largest infarct area on diffusion-weighted imaging (DWI) and T2 sequences were chosen. On the transverse plane of DWI and sagittal plane of T2-Flair images, the maximum length (a, m) and maximum width (b, n) vertical to the length of the infarcted lesions were measured respectively. On the sagittal plane of T2-Flair image, the maximum ventrodorsal length (f) and rostrocaudal thickness (h) were measured. On the sagittal plane, lesions were evenly split into upper, middle, and lower types based on the lesion's location in the pons. The ventral and dorsal types of location were separated based on whether the ventral borders of the pons were involved on transvers plane. END was defined as a ≥2 point increase in the National Institutes of Health Stroke Scale (NIHSS) total score or a ≥1 point increase in the motor items within 72 h after admission. Multivariate logistic regression analyses were used to explore risk factors associated with END. The receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) was performed to estimate the discriminative power and determine the optimal cut-off points of imaging parameters on the prediction of END. RESULTS: A total of 218 patients with AIPI were included in the final analysis. END occurred in 61 cases (28.0%). Multivariate logistic regression analysis showed that the ventral type of lesion location was associated with END in all models adjusted. In addition, in Model 1, b (odds ratio (OR) 1.145, 95% confidence interval (95% CI), 1.007-1.301) and n (OR 1.163, 95% CI 1.012-1.336); in Model 2, b*n (OR 1.010, 95% CI 1.002-1.018); in Model 3, n (OR 1.179, 95% CI, 1.028-1.353); and in Model 4, b (OR 1.143, 95% CI 1.006-1.298) and n (OR 1.167, 95% CI 1.016-1.341) were found to be associated with END respectively after different adjustments. ROC curve analysis with END showed that the AUC, the optimal cut-off value, and its sensitivity and specificity were 0.743 (0.671-0.815), 9.850 mm, and 68.9% and 79.0% for b; 0.724 (0.648-0.801), 10.800 mm, and 57.4% and 80.9% for n; and 0.772 (0.701-0.842), 108.274 mm2, and 62.3% and 85.4% for b*n, respectively (b*n vs b: P =0.213; b*n vs n: P =0.037; b vs n: P =0.645). CONCLUSIONS: Our study revealed that besides the ventral type of lesion location, the maximum width of lesion on the transverse plane of DWI and sagittal plane of T2 image (b, n) may be imaging markers for the development of END in AIPI patients, and the product of the two (b*n) showed a better prediction value on the risks of END.

The Novel Biomarkers-Based HALP (Hemoglobin, Albumin, Lymphocyte and Platelet)-Prognostic Model for Acute and Subacute Patients with Cerebral Venous Sinus Thrombosis: A Retrospective Cohort Study.

AIM: Increasing evidences suggest that HALP is an independent predictor of prognosis in patients with inflammation. However, the relationship between HALP and prognosis in patients with cerebral venous sinus thrombosis (CVST) has not been studied. In this study, we aimed to evaluate the prognosis values of HALP in acute or subacute CVST and explore the new prognostic model for CVST. METHODS: Consecutive patients who were diagnosed as having acute and subacute CVST were retrospectively investigated. We determined the patients' functional outcomes by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to assess the relationship between factors and poor functional outcomes. The area under the ROC curve (AUC) was estimated to evaluate the ability of markers and models in predicting clinical prognosis. The prognostic model was presented as nomogram. In addition, the decision curve analysis (DCA) was used to analyze the benefit of this model. Furthermore, survival curves were described by the Kaplan-Meier analysis. RESULTS: A total of 270 patients were included of which 31 had poor outcome. Multivariable logistic regression analysis demonstrated HALP (OR=0.978, 95%CI: 0.958-0.999, P=0.039) was a protective predictor of outcome. The AUC of HALP was 0.749 (95% CI: 0.633-0.865, P=0.044). DCA demonstrated that this model significantly improved risk prediction at threshold probabilities of CVST at 0 to 85% compared to ISCVT-RS scores. Patients with higher HALP (P=0.006) presented higher overall survival rates. CONCLUSION: HALP may be a potential protective marker in acute and subacute CVST patients. The new prognostic model with HALP had potentially better value for acute and subacute CVST patients.

Gasdermin D inhibition ameliorates neutrophil mediated brain damage in acute ischemic stroke.

Acute ischemic stroke (AIS) induces high level of neutrophils, which correlates inversely with patient survival. Pyroptosis induced by gasdermin D (GSDMD) has been shown to have an important role in the pathophysiology of several inflammatory disorders. The role of GSDMD in the high level of neutrophils after AIS is unknown. Using a middle cerebral artery occlusion (MCAO) mouse model, we identified activation of pyroptosis signal, including expression of caspase-1/11, GSDMD, and interleukin-1ß/18 (IL-1ß/18), in the brain and spleen at early ischemic injury. Knockout of GSDMD in mice reduced infarct size, improved neurological function, and increased survival after MCAO. GSDMD deficiency decreased the overall degree of inflammation and the proportion of neutrophils in the brain after MCAO. Quantitative studies of neutrophils at several time intervals and organs demonstrated that early inflammatory leucocyte production and supplement (1 day after MCAO) was GSDMD-dependent. A series of bone marrow transplantation experiments, neutrophil depletion experiments, and RNA sequencing results demonstrated that neutrophil specific GSDMD is essential for the production and supply of neutrophil in bone marrow to blood. Moreover, pharmacological suppression of GSDMD decreased pathological abnormalities, infarct volume, and ameliorated neurological function. These results provided a new viewpoint on the immunological modulation of neutrophils after MCAO and suggest that suppression of GSDMD may relieve the neuroinflammatory load, thereby providing a potential treatment strategy for stroke. The absence of GSDMD reduces the high level of neutrophils in the brain, the production of neutrophils in bone marrow, and the supply of blood and spleen, while simultaneously the neutrophil-specific GSDMD signal deficiency restrains leukocytosis to improve the pathological outcome of AIS.

Effects of Lactic Acid Bacteria Isolated from Equine on Salmonella-Infected Gut Mouse Model.

The aim of this study was to evaluate the antibacterial potential of lactic acid bacteria (Weissella confuse, Pediococcus acidilactici, and Ligilactobacillus equi) isolated from healthy equine in Wuhan against Salmonella Typhimurium CVCC542-induced mice model on intestinal microflora. In previous studies, these isolated strains showed good probiotic potentials in vitro. In this study, fifty healthy mice were randomly divided into five groups, the blank control group, the control group, the Pediococcus acidilactici group (1 × 108 CFU/day), the Ligilactobacillus equi group (1 × 108 CFU/day), and the Weissella confuse group (1 × 108 CFU/day). The body weight in control group and Weissella confuse group showed significant decreased (P < 0.05, P < 0.01), while Pediococcus acidilactici group and Ligilactobacillus equi group showed good recovering after treatments. The lowest diarrhea rate was shown in Ligilactobacillus equi group after treatment. In histopathology, Ligilactobacillus equi group showed the least structural damage in duodenum, and all probiotic treatment groups showed less damage in cecum. The sequence data and optical transform unit showed that Pediococcus acidilactici group and Ligilactobacillus equi group had higher number than control group, while the diversity data showed that the control group and Weissella confuse group had lower diversity in cecum. Microbial community analysis showed increased abundance of Firmicutes, Bacteroidetes, uncultured_bacterium_f_Muribaculaceae, and Lactobacillus in treatment groups, while potential microbes that can induce intestinal diseases such as Verrucomicrobia, Akkermansia, and Lachnospiraceae_NK4A136_group decreased in the treatment groups. In conclusion, lactic acid bacteria isolated from the healthy horses could alleviate the infection of Salmonella and regulate intestinal flora.

Lesion Location Predicts Early Neurological Deterioration in Single Subcortical Infarction.

BACKGROUND: A certain number of patients with single subcortical small infarction (SSSI) in the lenticulostriate artery (LSA) territory present with early neurological deterioration (END). OBJECTIVE: We sought to identify a more specific predicting imaging marker for END in lenticulostriate SSSI patients. METHODS: We screened patients in a prospective hospital-based registry of stroke in the first Affiliated Hospital of Zhengzhou University from January 2015 to December 2020. Lesion locations were defined as posterior type when more than half of the lesion was located in the posterior part of the corona radiata divided by the midline, which was drawn between the tangents of the anterior and posterior horns of the lateral ventricle and was adjacent to the lateral ventricle at the same time. END was defined as an increase of ≥2 points in total National Institutes of Health Stroke Scale score or ≥1 point. A multivariate logistic analysis was used to assess the imaging predictors for END. RESULTS: 418 patients were enrolled in the final data analysis. Among them, 206 (49. 3%) cases were rated as the posterior type and71 (17.0%) cases had to END. A multivariate logistic analysis showed that only the posterior type (adjusted odds ratio, 2. 126; 95% confidence interval, 1. 250-3. 614; P = 0. 005) was independently associated with the risk of END. CONCLUSION: The posterior type of lesion location represented an imaging marker predicting END in lenticulostriate SSSI patients.

A Bidirectional Mendelian Randomization Study of Selenium Levels and Ischemic Stroke.

Background: Previous observational studies have shown that circulating selenium levels are inversely associated with ischemic stroke (IS). Our aims were to evaluate the causal links between selenium levels and IS, and its subtypes by Mendelian randomization (MR) analysis. Methods: We used the two-sample Mendelian randomization (MR) method to determine whether the circulating selenium levels are causally associated with the risk of stroke. We extracted the genetic variants (SNPs) associated with blood and toenail selenium levels from a large genome-wide association study (GWAS) meta-analysis. Inverse variance-weighted (IVW) method was used as the determinant of the causal effects of exposures on outcomes. Results: A total of 4 SNPs (rs921943, rs6859667, rs6586282, and rs1789953) significantly associated with selenium levels were obtained. The results indicated no causal effects of selenium levels on ischemic stroke by MR analysis (OR = 0.968, 95% CI 0.914-1.026, p = 0.269). Meanwhile, there was no evidence of a causal link between circulating selenium levels and subtypes of IS. Conclusion: The MR study indicated no evidence to support the causal links between genetically predicted selenium levels and IS. Our results also did not support the use of selenium supplementation for IS prevention at the genetic level.

Effects of Short-Chain Fatty Acid Modulation on Potentially Diarrhea-Causing Pathogens in Yaks Through Metagenomic Sequencing.

Short-chain fatty acids (SCFA) are principal nutrient substrates of intestinal epithelial cells that regulate the epithelial barrier in yaks. Until now, metagenomics sequencing has not been reported in diarrheal yaks. Scarce information is available regarding the levels of fecal SCFA and diarrhea in yaks. So, our study aims to identify the potential pathogens that cause the emerging diarrhea and explore the potential relationship of short-chain fatty acids in this issue. We estimated diarrhea rate in yaks after collecting an equal number of fecal samples from affected animals. Metagenomics sequencing and quantitative analysis of SCFA were performed, which revealed 15%-25% and 5%-10% prevalence of diarrhea in yak's calves and adults, respectively. Violin box plot also showed a higher degree of dispersion in gene abundance distribution of diarrheal yaks, as compared to normal yaks. We found 366,163 significant differential abundance genes in diarrheal yaks, with 141,305 upregulated and 224,858 downregulated genes compared with normal yaks via DESeq analysis. Metagenomics binning analysis indicated the higher significance of bin 33 (Bacteroidales) (p < 0.05) in diarrheal animals, while bin 10 (p < 0.0001), bin 30 (Clostridiales) (p < 0.05), bin 51 (Lactobacillales) (p < 0.05), bin 8 (Lachnospiraceae) (p < 0.05), and bin 47 (Bacteria) (p < 0.05) were significantly higher in normal yaks. At different levels, a significant difference in phylum (n = 4), class (n = 8), oder (n = 8), family (n = 16), genus (n = 17), and species (n = 30) was noticed, respectively. Compared with healthy yaks, acetic acid (p < 0.01), propionic acid (p < 0.01), butyric acid (p < 0.01), isobutyric acid (p < 0.01), isovaleric acid (p < 0.05), and caproic acid (p < 0.01) were all observed significantly at a lower rate in diarrheal yaks. In conclusion, besides the increased Staphylococcus aureus, Babesia ovata, Anaplasma phagocytophilum, Bacteroides fluxus, viruses, Klebsiella pneumonia, and inflammation-related bacteria, the decrease of SCFA caused by the imbalance of intestinal microbiota was potentially observed in diarrheal yaks.

A Nomogram That Includes Neutrophils and High-Density Lipoprotein Cholesterol Can Predict the Prognosis of Acute Ischaemic Stroke.

Lipids are implicated in inflammatory responses affecting acute ischaemic stroke prognosis. Therefore, we aimed to develop a predictive model that considers neutrophils and high-density lipoprotein cholesterol to predict its prognosis. This prospective study enrolled patients with acute ischaemic stroke within 24 h of onset between January 2015 and December 2017. The main outcome was a modified Rankin Scale score ≥3 at the 90th day of follow-up. Patients were divided into training and testing sets. The training set was divided into four states according to the median of neutrophils and high-density lipoprotein cholesterol levels in all patients. Through binary logistic regression analysis, the relationship between factors and prognosis was determined. A nomogram based on the results was developed; its predictive value was evaluated through internal and external validations. Altogether, 1,090 patients were enrolled with 872 (80%) and 218 (20%) in the training and testing sets, respectively. In the training set, the major outcomes occurred in 24 (10.4%), 24 (11.6%), 37 (17.2%), and 49 (22.3%) in states 1-4, respectively (P = 0.002). Validation of calibration and decision curve analyses showed that the nomogram showed better performance. The internal and external testing set receiver operating characteristics verified the predictive value [area under the curve = 0.794 (0.753-0.834), P < 0.001, and area under the curve = 0.973 (0.954-0.992), P < 0.001, respectively]. A nomogram that includes neutrophils and high-density lipoprotein cholesterol can predict the prognosis of acute ischaemic stroke, thus providing us with an effective visualization tool.

Validation of CSR model to predict stroke risk after transient ischemic attack.

It is essential to identify high risk transient ischemic attack (TIA) patients. The previous study reported that the CSR (comprehensive stroke recurrence) model, a neuroimaging model, had a high predictive ability of recurrent stroke. The aims of this study were to validate the predictive value of CSR model in TIA patients and compare the predictive ability with ABCD3-I score. Data were analyzed from the prospective hospital-based database of patients with TIA which defined by the World Health Organization time-based criteria. The predictive outcome was stroke occurrence at 90 days. The receiver-operating characteristic (ROC) curves were plotted and the C statistics were calculated as a measure of predictive ability. Among 1186 eligible patients, the mean age was 57.28 ± 12.17 years, and 474 (40.0%) patients had positive diffusion-weighted imaging (DWI). There were 118 (9.9%) patients who had stroke within 90 days. In 1186 TIA patients, The C statistic of CSR model (0.754; 95% confidence interval [CI] 0.729-0.778) was similar with that of ABCD3-I score (0.717; 95% CI 0.691-0.743; Z = 1.400; P = 0.1616). In 474 TIA patients with positive DWI, C statistic of CSR model (0.725; 95% CI 0.683-0.765) was statistically higher than that of ABCD3-I score (0.626; 95% CI 0.581-0.670; Z = 2.294; P = 0.0245). The CSR model had good predictive value for assessing stroke risk after TIA, and it had a higher predictive value than ABCD3-I score for assessing stroke risk for TIA patients with positive DWI.

Interpretable CNN for ischemic stroke subtype classification with active model adaptation.

BACKGROUND: TOAST subtype classification is important for diagnosis and research of ischemic stroke. Limited by experience of neurologist and time-consuming manual adjudication, it is a big challenge to finish TOAST classification effectively. We propose a novel active deep learning architecture to classify TOAST. METHODS: To simulate the diagnosis process of neurologists, we drop the valueless features by XGB algorithm and rank the remaining ones. Utilizing active learning framework, we propose a novel causal CNN, in which it combines with a mixed active selection criterion to optimize the uncertainty of samples adaptively. Meanwhile, KL-focal loss derived from the enhancement of Focal loss by KL regularization is introduced to accelerate the iterative fine-tuning of the model. RESULTS: To evaluate the proposed method, we construct a dataset which consists of totally 2310 patients. In a series of sequential experiments, we verify the effectiveness of each contribution by different evaluation metrics. Experimental results show that the proposed method achieves competitive results on each evaluation metric. In this task, the improvement of AUC is the most obvious, reaching 77.4. CONCLUSIONS: We construct a backbone causal CNN to simulate the neurologist process of that could enhance the internal interpretability. The research on clinical data also indicates the potential application value of this model in stroke medicine. Future work we would consider various data types and more comprehensive patient types to achieve fully automated subtype classification.