Alteration in early resting­state functional MRI activity in comatose survivors of cardiac arrest: a prospective cohort study.

BACKGROUND: This study aimed to explore the characteristics of abnormal regional resting-state functional magnetic resonance imaging (rs-fMRI) activity in comatose patients in the early period after cardiac arrest (CA), and to investigate their relationships with neurological outcomes. We also explored the correlations between jugular venous oxygen saturation (SjvO2) and rs-fMRI activity in resuscitated comatose patients. We also examined the relationship between the amplitude of the N20-baseline and the rs-fMRI activity within the intracranial conduction pathway of somatosensory evoked potentials (SSEPs). METHODS: Between January 2021 and January 2024, eligible post-resuscitated patients were screened to undergo fMRI examination. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of rs-fMRI blood oxygenation level-dependent (BOLD) signals were used to characterize regional neural activity. Neurological outcomes were evaluated using the Glasgow-Pittsburgh cerebral performance category (CPC) scale at 3 months after CA. RESULTS: In total, 20 healthy controls and 31 post-resuscitated patients were enrolled in this study. The rs-fMRI activity of resuscitated patients revealed complex changes, characterized by increased activity in some local brain regions and reduced activity in others compared to healthy controls (P < 0.05). However, the mean ALFF values of the whole brain were significantly greater in CA patients (P = 0.011). Among the clusters of abnormal rs-fMRI activity, the cluster values of ALFF in the left middle temporal gyrus and inferior temporal gyrus and the cluster values of ReHo in the right precentral gyrus, superior frontal gyrus and middle frontal gyrus were strongly correlated with the CPC score (P < 0.001). There was a strong correlation between the mean ALFF and SjvO2 in CA patients (r = 0.910, P < 0.001). The SSEP N20-baseline amplitudes in CA patients were negatively correlated with thalamic rs-fMRI activity (all P < 0.001). CONCLUSIONS: This study revealed that abnormal rs-fMRI BOLD signals in resuscitated patients showed complex changes, characterized by increased activity in some local brain regions and reduced activity in others. Abnormal BOLD signals were associated with neurological outcomes in resuscitated patients. The mean ALFF values of the whole brain were closely related to SjvO2 levels, and changes in the thalamic BOLD signals correlated with the N20-baseline amplitudes of SSEP responses. TRIAL REGISTRATION: NCT05966389 (Registered July 27, 2023).

DL-3-n-butylphthalide-induced neuroprotection in rat models of asphyxia-induced cardiac arrest followed by cardiopulmonary resuscitation.

Most patients that resuscitate successfully from cardiac arrest (CA) suffer from poor neurological prognosis. DL-3-n-butylphthalide (NBP) is known to have neuroprotective effects via multiple mechanisms. This study aimed to investigate whether NBP can decrease neurological impairment after CA. We studied the protective role of NBP in the hippocampus of a rat model of cardiac arrest induced by asphyxia. Thirty-nine rats were divided randomly into sham, control, and NBP groups. Rats in control and NBP groups underwent cardiopulmonary resuscitation (CPR) 6 min after asphyxia. NBP or vehicle (saline) was administered intravenously 10 min after the return of spontaneous circulation (ROSC). Ultrastructure of hippocampal neurons was observed under transmission electron microscope. NBP treatment improved neurological function up to 72 h after CA. The ultrastructural lesion in mitochondria recovered in the NBP-treated CA model. In conclusion, our study demonstrated multiple therapeutic benefits of NBP after CA.

Leukocyte glucocorticoid receptor expression and related transcriptomic gene signatures during early sepsis.

PURPOSE: The study aimed to understand the molecular mechanisms that might lead to differences in the glucocorticoid response during sepsis. METHODS: Patients diagnosed with sepsis (n = 198) and 40 healthy controls were enrolled. Glucocorticoid receptor (GR) expression in circulating leukocytes and plasma levels of adrenocorticotropic hormone and cortisol on days 1 and 7 were measured in all participants. Expression profiling of 16 genes associated with GR expression in peripheral blood mononuclear cells (PBMCs) in 12 healthy controls and 26 patients with sepsis was performed by PCR. RESULTS: Cortisol levels were higher in patients with sepsis than in healthy controls on day 1 after admission and recovered to normal levels by day 7. GR expression was gradually downregulated in leukocyte subsets. Non-survivors showed lower GR and higher cortisol levels than survivors. GRα expression was lower in patients with sepsis than in controls, whereas GRß showed the opposite trend. MicroRNAs related to GR resistance and suppression were altered in PBMCs during sepsis. CONCLUSION: Patients with sepsis showed upregulated plasma cortisol levels along with downregulated GR expression on various leukocyte subtypes, portending poor cortisol response and outcome. Changes in GR-regulatory miRNAs may be responsible for GR low expression.

Conjunctival microcirculation is associated with cerebral cortex microcirculation in post-resuscitation mild hypothermia: A rat model.

OBJECTIVE: This study aimed to compare the changes in sublingual and conjunctival microcirculation occurring with cerebral cortex microcirculation changes during mild hypothermia in a rat model of cardiac arrest. METHODS: Twenty-four rats were randomized into mild hypothermia (M) or normothermia (C) groups. Ventricular fibrillation was electrically induced and left untreated for 8 minutes, followed by 8 minutes of cardiopulmonary resuscitation. The core temperature in group M reduced to 33 ± 0.5°C at 13 minutes after restoration of spontaneous circulation and was maintained for 8 hours. In group C, the core temperature was maintained at 37 ± 0.2°C. The hemodynamics and microcirculation in the sublingual region, bulbar conjunctiva, and cerebral cortex were measured at baseline and 1, 2, 3, 4, 6, and 8 hours after restoration of spontaneous circulation. RESULTS: The M group showed significantly worse sublingual microcirculation at 6 hours post-resuscitation. However, microcirculation in the conjunctiva and cerebral cortex at 3 hours post-resuscitation were better in the M group. In the M group, microcirculation in the cerebral cortex was significantly correlated with that in the conjunctiva but not the sublingual microcirculation. CONCLUSIONS: Changes in conjunctival microcirculation are closely related to cerebral cortex microcirculation during mild hypothermia, indicating that cerebral cortex microcirculation could be monitored by measuring conjunctival microcirculation.

Development and validation of prognosis model of mortality risk in patients with COVID-19.

This study aimed to identify clinical features for prognosing mortality risk using machine-learning methods in patients with coronavirus disease 2019 (COVID-19). A retrospective study of the inpatients with COVID-19 admitted from 15 January to 15 March 2020 in Wuhan is reported. The data of symptoms, comorbidity, demographic, vital sign, CT scans results and laboratory test results on admission were collected. Machine-learning methods (Random Forest and XGboost) were used to rank clinical features for mortality risk. Multivariate logistic regression models were applied to identify clinical features with statistical significance. The predictors of mortality were lactate dehydrogenase (LDH), C-reactive protein (CRP) and age based on 500 bootstrapped samples. A multivariate logistic regression model was formed to predict mortality 292 in-sample patients with area under the receiver operating characteristics (AUROC) of 0.9521, which was better than CURB-65 (AUROC of 0.8501) and the machine-learning-based model (AUROC of 0.4530). An out-sample data set of 13 patients was further tested to show our model (AUROC of 0.6061) was also better than CURB-65 (AUROC of 0.4608) and the machine-learning-based model (AUROC of 0.2292). LDH, CRP and age can be used to identify severe patients with COVID-19 on hospital admission.

The neutrophil-to-lymphocyte ratio levels over time correlate to all-cause hospital mortality in sepsis.

Objective: This research aims to investigate the prognosis value using the time-weighted average neutrophil-to-lymphocyte ratio (TWA-NLR) for predicting all-cause hospital mortality among sepsis patients. Data were analyzed through the use of the eICU Collaborative Research Database (eICU-CRD 2.0) as well as Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2). Methods: Septic patients from both eICU-CRD 2.0 as well as MIMIC-IV 2.2 databases were included. The neutrophil-to-lymphocyte ratios (NLR) were available for analysis, utilizing complete blood counts obtained on days one, four, and seven following ICU admission. The TWA-NLR was computed at the end of the seven days, and patients were then stratified based on TWA-NLR thresholds. 90-day all-cause mortality during hospitalization was the primary objective, with 60-day all-cause hospital mortality as a secondary objective. The correlation between TWA-NLR and sepsis patients' primary outcome was analyzed using univariable and multivariable Cox proportional hazard regressions. A restricted cubic spline (RCS) analysis was conducted in an attempt to confirm this association further, and subgroup analyses were employed to evaluate the correlation across various comorbidity groups. Results: 3921 patients were included from the eICU-CRD 2.0, and the hospital mortality rate was 20.8 %. Both multivariable as well as univariable Cox proportional hazard regression analyses revealed that TWA-NLR was independently correlated with 90-day all-cause hospital mortality, yielding a hazard ratio (HR) of 1.02 (95 % CI 1.01-1.02, P-value<0.01) as well as 1.12 (95 % CI 1.01-1.15, P-value<0.01), respectively. The RCS analysis demonstrated a significant nonlinear relationship between TWA-NLR and 90-day all-cause hospital mortality risk. The study subjects were divided into higher (>10.5) and lower (≤10.5) TWA-NLR cohorts. A significantly decreased incidence of 90-day all-cause hospital mortality (HR = 0.56, 95 % CI 0.48-0.64, P-value<0.01) and longer median survival time (40 days vs 24 days, P-value<0.05) were observed in the lower TWA-NLR cohort. However, septic patients with chronic pulmonary (interaction of P-value = 0.009) or renal disease (interaction of P-value = 0.008) exhibited significant interactive associations between TWA-NLR and 90-day all-cause hospital mortality, suggesting the predictive power of TWA-NLR may be limited in these subgroups. The MIMIC-IV 2.2 was utilized as a validation cohort and exhibited a similar pattern. Conclusion: Our findings suggest that TWA-NLR is a powerful and independent prognostic indicator for 90-day all-cause hospital mortality among septic patients, and the TWA-NLR cutoff value may prove a useful method for identifying high-risk septic patients.

U-shaped correlation of lymphocyte count with all-cause hospital mortality in sepsis and septic shock patients: a MIMIC-IV and eICU-CRD database study.

BACKGROUND: In sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocytopenia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in responding to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts correlate with all-cause hospital mortality among sepsis patients. METHODS: This retrospective cohort study analyzed data from two extensive critical care databases: the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lymphocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess lymphocyte counts' impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various comorbidity groups among sepsis and septic shock patients. RESULTS: Our study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable and multivariable Cox proportional hazard regression models showed that lymphocyte counts were independently associated with in-hospital mortality (HR = 1.04, P < 0.01; HR = 1.06, P < 0.01). RCS regression analysis revealed a U-shaped relationship between lymphocyte levels and hospital mortality risk in sepsis and septic shock patients (P for overall < 0.001, P for nonliner < 0.01; P for overall = 0.002, P for nonliner = 0.014). Subgroup analyses revealed that elevated lymphocyte counts correlated with increased hospital mortality among sepsis patients with liver disease and requiring renal replacement therapy (P for overall = 0.021, P for nonliner = 0.158; P for overall = 0.025, P for nonliner = 0.759). These findings suggest that lymphocytes may have enhanced prognostic value in specific subsets of critically ill sepsis patients. CONCLUSION: Our findings demonstrate that lymphocyte counts are a significant independent predictor of hospital mortality in sepsis and septic shock patients. We observed a U-shaped association between lymphocyte levels and mortality risk, indicating that high and low counts are linked to increased mortality. This result highlights the complex role of lymphocytes in sepsis outcomes and suggests the need for further investigation into the underlying mechanisms and potential therapeutic approaches. Integrating lymphocyte count assessment into risk stratification algorithms and clinical decision support tools could enhance the early identification of high-risk sepsis patients.

Predicting sepsis in-hospital mortality with machine learning: a multi-center study using clinical and inflammatory biomarkers.

BACKGROUND: This study aimed to develop and validate an interpretable machine-learning model that utilizes clinical features and inflammatory biomarkers to predict the risk of in-hospital mortality in critically ill patients suffering from sepsis. METHODS: We enrolled all patients diagnosed with sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.0), eICU Collaborative Research Care (eICU-CRD 2.0), and the Amsterdam University Medical Centers databases (AmsterdamUMCdb 1.0.2). LASSO regression was employed for feature selection. Seven machine-learning methods were applied to develop prognostic models. The optimal model was chosen based on its accuracy, F1 score and area under curve (AUC) in the validation cohort. Moreover, we utilized the SHapley Additive exPlanations (SHAP) method to elucidate the effects of the features attributed to the model and analyze how individual features affect the model's output. Finally, Spearman correlation analysis examined the associations among continuous predictor variables. Restricted cubic splines (RCS) explored potential non-linear relationships between continuous risk factors and in-hospital mortality. RESULTS: 3535 patients with sepsis were eligible for participation in this study. The median age of the participants was 66 years (IQR, 55-77 years), and 56% were male. After selection, 12 of the 45 clinical parameters collected on the first day after ICU admission remained associated with prognosis and were used to develop machine-learning models. Among seven constructed models, the eXtreme Gradient Boosting (XGBoost) model achieved the best performance, with an AUC of 0.94 and an F1 score of 0.937 in the validation cohort. Feature importance analysis revealed that Age, AST, invasive ventilation treatment, and serum urea nitrogen (BUN) were the top four features of the XGBoost model with the most significant impact. Inflammatory biomarkers may have prognostic value. Furthermore, SHAP force analysis illustrated how the constructed model visualized the prediction of the model. CONCLUSIONS: This study demonstrated the potential of machine-learning approaches for early prediction of outcomes in patients with sepsis. The SHAP method could improve the interoperability of machine-learning models and help clinicians better understand the reasoning behind the outcome.

Effects of hypothermia on brain injury assessed by magnetic resonance imaging after cardiopulmonary resuscitation in a porcine model of cardiac arrest.

OBJECTIVE: To evaluate the effects of hypothermia on cerebral edema and metabolism, a porcine model of cardiac arrest was assessed by magnetic resonance imaging during the first 72 hours after restoration of spontaneous circulation (ROSC). METHODS: Ventricular fibrillation was induced in 33 pigs. After 8 minutes of untreated ventricular fibrillation, 30:2 cardiopulmonary resuscitation was performed. After ROSC, 30 survival animals were randomly divided into normothermia group (n = 15) and hypothermia group (n = 15). The hypothermia group immediately received endovascular cooling to regulate temperature to 33°C, which was maintained for 12 hours, followed by passive rewarming at 0.5°C/h to 37°C. Diffusion-weighted imaging and (1)hydrogen proton magnetic resonance spectroscopy were acquired for each group at 6, 12, 24, and 72 hours after ROSC. RESULTS: Compared with the normothermia group, the hypothermia group exhibited a higher 72-hour survival (73.3% vs. 33.3%, P = .028) and a superior neurological deficit score (P = .031). Cerebral injury was found in both groups, but a lesser decrease in the apparent diffusion coefficient and N-acetyl aspartate/creatinine (P < .05) and a greater increase in choline/creatinine (P < .05) were found in the hypothermia group. CONCLUSIONS: Magnetic resonance imaging could effectively detect the dynamic trend of cerebral injury in a porcine model of cardiac arrest within the first 72 hours after ROSC. Hypothermia produced a protective effect on neurological function by reducing brain edema and formation of adverse metabolites.

[Research progress of target temperature management on protective mechanism of cardiac function after cardiac arrest].

Targeted temperature management (TTM) has been partially applied in patients with restoration of spontaneous circulation (ROSC) after cardiac arrest (CA). In the 2020 American Heart Association (AHA) cardiopulmonary resuscitation (CPR) guidelines, TTM is used as advanced life support after ROSC for the treatment of patients with CPR. TTM has a protective effect on cardiac function after CA, but the specific mechanism of its protective effect on cardiac function remains unclear. In this paper, the basic experimental progress, clinical trial progress and development prospect of TTM on the protective mechanism of cardiac function after CA are reviewed.

Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study.

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis. METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay. RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality. CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

Donor-Derived Infection's Prevention and Control in Kidney Transplantation.

BACKGROUND: The study aimed to summarize the experience of donor selection and recipient therapy in the face of potential donor-derived infections and improve the quality of donor organ utilization, which would help reduce the risk of infection after recipient operation and decrease the risk of loss or even death of recipient kidney transplantation. METHODS: In this study, 132 kidneys from 70 donors and their recipients who underwent surgery between July 2017 and January 2021 were studied to perform a retrospective analysis of their etiologic examination results and treatment process. RESULTS: In the 70 donors, only 25 had negative etiologic examination results, accounting for 35.71%. Among the 132 recipients, 31.82% had positive culture results, 3 (2.27%) experienced donor-derived infections, and one died. CONCLUSIONS: Although infection in the donor before the donation is quite common, the incidence of donor-derived infections is relatively low. The targeted and preventive application of adequate sensitive antibiotics in the whole course of therapy was the cornerstone for treating recipients at potential risk of potential donor-derived infection. The changes in infection indicators in the recipient should be closely monitored, which would guide medication adjustments timely. These measures could, to a great degree, ensure the prognosis of the recipient, in turn reducing the adverse events caused by donor-derived infections.

Cerebrospinal fluid biochemistry reflects effects of therapeutic hypothermia after cardiac arrest in a porcine model.

BACKGROUND: Mild induced hypothermia (MIH) is recommended to treat neurologic injury after cardiac arrest (CA). However, clinical trials to assess MIH benefit after CA have been largely inconclusive. We investigated the subsequent changes in cerebrospinal fluid (CSF) biochemistry after MIH (33°C-34°C for 12 hours) and evaluated the importance of ongoing fever control. METHODS: Thirty-two male Wuzhishan inbred mini pigs (n = 16/group) underwent ventricular fibrillation followed by cardiopulmonary resuscitation and were randomized into 2 groups: hypothermic and control. Upon resumption of spontaneous circulation (ROSC) from CA, the hypothermic group was treated with MIH by endovascular cooling. The control group received no temperature intervention. Core temperatures were continually monitored. At various points throughout the procedure, CSF samples were obtained to measure glutamate, lactate, and pyruvate levels. RESULTS: The core temperature of the hypothermic group was found to have increased postrewarming and reached levels comparable with those of the control group at ROSC 72 hours. In both groups, glutamate increased significantly after ROSC, but the glutamate levels in the hypothermic group were lower than those in the control group, except at ROSC 1 hour. The lactate-pyruvate ratio increased in the control group at ROSC 1 hour and was significantly lower in the hypothermic group (P < .05). CONCLUSIONS: Mild induced hypothermia mitigated and delayed the CA-induced increase of CSF glutamate. Therefore, our results suggest that clinically inducing hypothermia as soon as possible after CA, or prolonging the time of MIH in combination with controlling ongoing fever, may enhance hypothermic protective effects.

Glucocorticoid receptor expression in patients with cardiac arrest in the early period after the return of spontaneous circulation: a prospective observational single-centre study.

OBJECTIVES: Rapid changes in glucocorticoid (GC) levels and adrenal insufficiency are related to the development of post-cardiac arrest (CA) syndrome. However, GC receptor (GR) expression changes have not been studied. Hence, this study aimed to investigate the association of early changes in GR expression and prognosis and immune response in patients who experienced CA. DESIGN: Prospective observational study. SETTING: Emergency department. PARTICIPANTS: Patients (85) in the early period of return of spontaneous circulation (ROSC) after CA were admitted between October 2018 and October 2019. After a physical examination, age-matched and sex-matched healthy individuals (40) were recruited for the control group. PRIMARY AND SECONDARY OUTCOME MEASURES: GR expression and cell counts of circulatory T and B lymphocytes, natural killer cells and regulatory T (Treg) cells were assessed. Plasma total cortisol and adrenocorticotrophic hormone (ACTH) levels were also tested. RESULTS: All cell counts were lower, and plasma total cortisol levels were higher (p<0.001) in patients who experienced CA than in the healthy control group. GR expression in Treg cells and CD3+CD4+ T lymphocytes were not significantly different, but the mean fluorescence intensity and GR expression in other cells were lower in patients who experienced CA (p<0.05) than in the healthy control group. ACTH levels were not different. There were no significant differences between survivors and non-survivors. CONCLUSIONS: This study revealed that GR expression and cell counts rapidly decreased, whereas plasma total cortisol levels increased in the early period after ROSC among patients who experienced CA. Our findings provide important information about GR level and function, and immunosuppressive status in these patients. Assessing GR expression in patients who experienced CA may help screening for those who are more sensitive to GC therapy.

Acidosis in arterial blood gas testing is associated with clinical outcomes after endovascular thrombectomy.

Background: Despite recanalization, some of the patients undergoing endovascular thrombectomy (EVT) still suffer from unfavorable outcomes. Patients with poor prognoses are often accompanied by acidosis in arterial blood gas (ABG) testing. We, therefore, explored the ABG testing results in the early phase of recanalization and analyzed their association with poor prognosis. Patients and methods: We identified all patients with ischemic stroke and successful endovascular recanalization for anterior circulation vessel occlusion between June 2019 and May 2022. ABG testing was performed in all patients within 0-30 min and 8 h after endovascular therapy. We investigated the relationship between the ABG testing results with symptomatic intracerebral hemorrhage (sICH), hemicraniectomy, and mortality. Results: A total of 123 patients with stroke after endovascular thrombectomy were analyzed. Of those, eight (6.5%) patients had postinterventional sICH. Acidosis was associated with sICH. Decreased HCO 3 - levels and HCO 3 - levels at 8 h after EVT were independently related to a higher risk of sICH. Twelve (9.8%) patients underwent hemicraniectomy for postischemic malignant edema and similar results were found for hemicraniectomy. Increased lactate at 8 h after EVT and decreased HCO 3 - levels at 8 h after EVT were closely associated with hemicraniectomy. Twenty-two (17.9%) patients died within 3 months. Decreased HCO 3 - levels were independently related to mortality, as were decreased pH levels at 8 h after EVT and decreased HCO 3 - levels at 8 h after EVT. Conclusion: Acidosis is associated with clinical outcomes after endovascular therapy and may help to select patients with poor prognosis in the acute early phase of recanalization.

Potential Value of Presepsin Guidance in Shortening Antibiotic Therapy in Septic Patients: a Multicenter, Prospective Cohort Trial.

INTRODUCTION: Long-term use of antibiotics for septic patients leads to bacterial resistance, increased mortality, and hospital stay. In this study, we investigated an emerging biomarker presepsin-guided strategy, which can be used to evaluate the shortening of antibiotic treatment in patients with sepsis without risking a worse outcome. METHODS: In this multicenter prospective cohort trial, patients were assigned to the presepsin or control groups. In the presepsin group, antibiotics were ceased based on predefined cut-off ranges of presepsin concentrations. The control group stopped antibiotics according to international guidelines. The primary endpoints were the number of days without antibiotics within 28 days and mortality at 28 and 90 days. Secondary endpoints were the percentage of patients with a recurrent infection, length of stay in ICU and hospital, hospitalization costs, days of first episode of antibiotic treatment, percentage of antibiotic administration and multidrug-resistant bacteria, and SOFA score. RESULTS: Overall, 656 out of an initial 708 patients were eligible and assigned to the presepsin group (n = 327) or the control group (n = 329). Patients in the presepsin group had significantly more days without antibiotics than those in the control group (14.54 days [SD 9.01] vs. 11.01 days [SD 7.73]; P < 0.001). Mortality in the presepsin group showed no difference to that in the control group at days 28 (17.7% vs. 18.2%; P = 0.868) and 90 (19.9% vs. 19.5%; P = 0.891). Patients in the presepsin group had a significantly shorter mean length of stay in the hospital and lower hospitalization costs than control subjects. There were no differences in the rate of recurrent infection and multidrug-resistant bacteria and the SOFA score tendency between the two groups. CONCLUSIONS: Presepsin guidance has potential to shorten the duration of antibiotic treatment in patients with sepsis without risking worse outcomes of death, recurrent infection, and aggravation of organ failure. TRIAL REGISTRATION: ChiCTR, ChiCTR1900024391. Registered 9 July 2019-Retrospectively registered, http://www.chictr.org.cn.

Development and evaluation of a predictive nomogram for survival in heat stroke patients: a retrospective cohort study.

BACKGROUND: This study aimed to establish an effective nomogram to predict the survival of heat stroke (HS) based on risk factors. METHODS: This was a retrospective, observational multicenter cohort study. We analyzed patients diagnosed with HS, who were treated between May 1 and September 30, 2018 at 15 tertiary hospitals from 11 cities in Northern China. RESULTS: Among the 175 patients, 32 patients (18.29%) died before hospital discharge. After the univariate analysis, mechanical ventilation, initial mean arterial pressure <70 mmHg, maximum heart rate, lab results on day 1 (white blood cell count, alanine aminotransferase, creatinine), and Glasgow admission prediction score were included in multivariate analysis. Multivariate Cox regression showed that invasive ventilation, initial mean arterial pressure <70 mmHg (1 mmHg=0.133 kPa), and Glasgow admission prediction score were independent risk factors for HS. The nomogram was established for predicting 7-d and 14-d survival in the training cohort. The nomogram exhibited a concordance index (C-index) of 0.880 (95% confidence interval [95% CI] 0.831-0.930) by bootstrapping validation (B=1,000). Furthermore, the nomogram performed better when predicting 14-d survival, compared to 7-d survival. The prognostic index cut-off value was set at 2.085, according to the operating characteristic curve for overall survival prediction. The model showed good calibration ability in the internal and external validation datasets. CONCLUSION: A novel nomogram, integrated with prognostic factors, was proposed; it was highly predictive of the survival in HS patients.

Effects of Different Target Temperatures on Angiogenesis and Neurogenesis Following Resuscitation in a Porcine Model After Cardiac Arrest.

OBJECTIVE: The optimal effective temperature of targeted temperature management (TTM) used to prevent cerebral injury following cardiopulmonary resuscitation (CPR) is undetermined. In this study, we compared the mortality, neurologic deficits, and cerebral protein levels of two target temperatures. METHODS: Fifty 4-month-old female domestic pigs were randomized to sham, TTM at 33°C ±â€Š0.5°C (T33), TTM at 35°C ±â€Š0.5°C (T35), and normothermic (NT) groups. In the NT and TTM groups, untreated ventricular fibrillation was induced electrically in animals for 10 min, followed by 6 min of CPR. Target core temperatures (Tc) of TTM groups were induced and maintained (6 h) using an endovascular hypothermia device, and rewarmed to 37.5 ±â€Š0.5°C in the next 6 h. Tc of the NT group was maintained at 37.5 ±â€Š0.5°C. The survival outcomes and neurological function were evaluated every 24 h for 72 h. RESULTS: All animals were successfully resuscitated with no significant differences in baseline characteristics or hemodynamic indexes. Survival rates and neurological outcomes were significantly improved in the TTM groups, with T33 showing the most significant effect. Compared with NT-treated animals, TTM-treated animals had higher expressions of angiopoietin-1, transforming growth factor-alpha , vascular endothelial growth factor, metallopeptidase inhibitor (TIMP)-1, TIMP-2, and platelet-derived growth factor-BB. Macrophage migration inhibitory factor and IL-17F levels were markedly upregulated after resuscitation in the NT group but inhibited in the TTM groups. Neuron-specific enolase staining data was also consistent with our conclusion that hypothermia can reduce reperfusion-induced brain injuries. CONCLUSION: Lower target temperature showed greater protective effects against cerebral injuries after CPR, and the improved neurological outcomes after TTM may be associated with decreased expression of pro-inflammatory cytokines and increased expression of blood-brain barrier and neurogenesis regulatory factors in this porcine model of CA following resuscitation.

Efficacy of Qingfei Paidu Decoction on Patients with COVID-19 Pneumonia in Wuhan, China: A Propensity Score Matching Study.

BACKGROUND: In view of the global efforts to develop effective treatments for the current worldwide coronavirus 2019 (COVID-19) pandemic, Qingfei Paidu decoction (QPD), a novel traditional Chinese medicine (TCM) prescription, was formulated as an optimized combination of constituents of classic prescriptions used to treat numerous febrile and respiratory-related diseases. This prescription has been used to treat patients with COVID-19 pneumonia in Wuhan, China. Hypothesis/Purpose. We hypothesized that QPD would have beneficial effects on patients with COVID-19. We aimed to prove this hypothesis by evaluating the efficacy of QPD in patients with COVID-19 pneumonia. METHODS: In this single-center, retrospective, observational study, we identified eligible participants who received a laboratory diagnosis of COVID-19 between January 15 and March 15, 2020, in the west campus of Union Hospital in Wuhan, China. QPD was supplied as an oral liquid packaged in 200-mL containers, and patients were orally administered one package twice daily 40 minutes after a meal. The primary outcome was death, which was compared between patients who did and did not receive QPD (QPD and NoQPD groups, respectively). Propensity score matching (PSM) was used to identify cohorts. RESULTS: In total, 239 and 522 participants were enrolled in the QPD and NoQPD groups, respectively. After PSM at a 1 : 1 ratio, 446 patients meeting the criteria were included in the analysis with 223 in each arm. In the QPD and NoQPD groups, 7 (3.2%) and 29 (13.0%) patients died, and those in the QPD group had a significantly lower risk of death (hazard ratio (HR) 0.29, 95% CI: 0.13-0.67) than those in the NoQPD group (p = 0.004). Furthermore, the survival time was significantly longer in the QPD group than in the NoQPD group (p < 0.001). CONCLUSION: The use of QPD may reduce the risk of death in patients with COVID-19 pneumonia.

Hypothermia-Induced Ubiquitination of Voltage-Dependent Anion Channel 3 Protects BV2 Microglia Cells From Cytotoxicity Following Oxygen-Glucose Deprivation/Recovery.

Background: Hypothermia attenuates microglial activation and exerts a potential neuroprotective effect against cerebral ischemic-reperfusion (I/R) injury. However, the underlying mechanism remains to be elucidated. In this in vitro study, a model of oxygen-glucose deprivation, followed by recovery (OGD/R), was used to investigate whether hypothermia exerts anti-inflammatory and anti-apoptosis properties via enhanced ubiquitination and down-regulation of voltage-dependent anion channel 3 (VDAC3) expression. Methods: BV2 microglia were cultured under OGD for 4 h following reperfusion with or without hypothermia for 2, 4, or 8 h. M1 and M2 microglia markers [inducible nitric oxide synthase (iNOS) and arginase (Arg)1] were detected using immunofluorescence. The levels of pro-inflammatory cytokines [tumor necrosis factor (TNF) α, interleukin (IL)-1ß], and anti-inflammatory factor (IL-10) were determined using enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was assayed by JC-1 staining using a flow cytometer. Expression of caspase-3, cleaved caspase-3, and VDAC3 were assessed using western blot analysis. The cellular locations and interactions of ubiquitin and VDAC3 were identified using double immunofluorescence staining and immunoprecipitation (IP) assay. Also, the level of the VDAC3 mRNA was determined using a quantitative polymerase chain reaction (qPCR). Results: Hypothermia inhibited the OGD/R-induced microglia activation and differentiation into the M1 type with pro-inflammatory effect, whereas it promoted differentiation to the M2 type with anti-inflammatory effect. Hypothermia attenuated OGD/R-induced loss of Δψm, as well as the expression of apoptosis-associated proteins. Compared to normothermia, hypothermia increased the level of ubiquitinated VDAC3 in the BV2 microglia at both 2 and 8 h of reperfusion. Furthermore, hypothermia did not attenuate VDAC3 mRNA expression in OGD/R-induced microglia. Conclusions: Hypothermia treatment during reperfusion, attenuated OGD/R-induced inflammation, and apoptosis in BV2 microglia. This might be due to the promotion of VDAC3 ubiquitination, identifying VDAC3 as a new target of hypothermia.