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Anti-NMDA Receptor Autoantibody Is an Independent Predictor of Hospital Mortality but Not Brain Dysfunction in Septic Patients.

ABSTRACT: The presence of autoantibodies against neuronal cell surface or synaptic proteins and their relationship to autoimmune encephalitis have recently been characterized. These autoantibodies have been also reported in other pathologic conditions; however, their role during sepsis is not known. This study detected the presence of autoantibodies against neuronal cell surface or synaptic proteins in the serum of septic patients and determined their relationship to the occurrence of brain dysfunction and mortality. This prospective, observational cohort study was performed in four Brazilian intensive care units (ICUs). Sixty patients with community-acquired severe sepsis or septic shock admitted to the ICU were included. Blood samples were collected from patients within 24 h of ICU admission. Antibodies to six neuronal proteins were assessed, including glutamate receptors (types NMDA, AMPA1, and AMPA2); voltage-gated potassium channel complex (VGKC) proteins, leucine-rich glioma-inactivated protein 1 (LGI1), and contactin-associated protein-2 (Caspr2), as well as the GABAB1 receptor. There was no independent association between any of the measured autoantibodies and the occurrence of brain dysfunction (delirium or coma). However, there was an independent and significant relationship between anti-NMDAR fluorescence intensity and hospital mortality. In conclusion, anti-NMDAR was independently associated with hospital mortality but none of the measured antibodies were associated with brain dysfunction in septic patients.

SUBMITTER: Malfussi H

PROVIDER: S-EPMC6428735 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Anti-NMDA Receptor Autoantibody Is an Independent Predictor of Hospital Mortality but Not Brain Dysfunction in Septic Patients.

Malfussi Hamilton H Santana Iara Vidigal IV Gasparotto Juciano J Righy Cassia C Tomasi Cristiane Damiani CD Gelain Daniel Pens DP Bozza Fernando A FA Walz Roger R Dal-Pizzol Felipe F Ritter Cristiane C

Frontiers in neurology 20190315

The presence of autoantibodies against neuronal cell surface or synaptic proteins and their relationship to autoimmune encephalitis have recently been characterized. These autoantibodies have been also reported in other pathologic conditions; however, their role during sepsis is not known. This study detected the presence of autoantibodies against neuronal cell surface or synaptic proteins in the serum of septic patients and determined their relationship to the occurrence of brain dysfunction an ...[more]

PMID: 30930837

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Project description:Background and Objectives: Neutrophil-to-lymphocyte ratio (NLR), a very low cost, widely available marker of systemic inflammation, has been proposed as a potential predictor of short-term outcome in patients with intracerebral hemorrhage (ICH). Methods: Patients with ICH admitted to the Neurology Department during a two-year period were screened for inclusion. Based on eligibility criteria, 201 patients were included in the present analysis. Clinical, imaging, and laboratory characteristics were collected in a prespecified manner. Logistic regression models and receiver operating characteristics (ROC) curves were used to assess the performance of NLR assessed at admission (admission NLR) and 72 h later (three-day NLR) in predicting in-hospital death. Results: The median age of the study population was 70 years (IQR: 61-79), median admission NIHSS was 16 (IQR: 6-24), and median hematoma volume was 13.7 mL (IQR: 4.6-35.2 mL). Ninety patients (44.8%) died during hospitalization, and for 35 patients (17.4%) death occurred during the first three days. Several common predictors were significantly associated with in-hospital mortality in univariate analysis, including NLR assessed at admission (OR: 1.11; 95% CI: 1.04-1.18; p = 0.002). However, in multivariate analysis admission, NLR was not an independent predictor of in-hospital mortality (OR: 1.04; 95% CI: 0.9-1.1; p = 0.3). The subgroup analysis of 112 patients who survived the first 72 h of hospitalization showed that three-day NLR (OR: 1.2; 95% CI: 1.09-1.4; p < 0.001) and age (OR: 1.05; 95% CI: 1.02-1.08; p = 0.02) were the only independent predictors of in-hospital mortality. ROC curve analysis yielded an optimal cut-off value of three-day NLR for the prediction of in-hospital mortality of ≥6.3 (AUC = 0.819; 95% CI: 0.735-0.885; p < 0.0001) and Kaplan-Meier analysis proved that ICH patients with three-day NLR ≥6.3 had significantly higher odds of in-hospital death (HR: 7.37; 95% CI: 3.62-15; log-rank test; p < 0.0001). Conclusion: NLR assessed 72 h after admission is an independent predictor of in-hospital mortality in ICH patients and could be widely used in clinical practice to identify the patients at high risk of in-hospital death. Further studies to confirm this finding are needed.

Project description:ObjectivesCirculatory dysfunction has been associated with mortality in children with septic shock. However, the mortality risk attributable to myocardial dysfunction per se has not been established, and the association between myocardial dysfunction and mortality is confounded by illness severity. The objective was to determine if sepsis-associated myocardial dysfunction defined by low left ventricular ejection fraction or global longitudinal strain is associated with mortality in pediatric septic shock after adjusting for baseline mortality probability.DesignRetrospective, observational study.SettingSingle-center, quaternary-care PICU.PatientsChildren less than 18 years old admitted to the PICU from 2003 to 2018 who had an echocardiogram performed within 48 hours of septic shock identification and Pediatric Sepsis Biomarker Risk Model II data available.InterventionsNone.Measurements and main resultsAll echocardiograms were reread by a cardiologist blinded to patient data for left ventricular ejection fraction and global longitudinal strain. Low left ventricular ejection fraction was defined as less than 45%, and low global longitudinal strain was defined as greater than z score of -2 for body surface area. Multivariable logistic regression separately analyzed the associations of low left ventricular ejection fraction and low global longitudinal strain with mortality, adjusting for Pediatric Sepsis Biomarker Risk Model II mortality risk. A post hoc logistic regression analyzed the association of left ventricular ejection fraction as a continuous variable with mortality, where linearity was maintained for left ventricular ejection fraction less than 65%. Eighteen percent of 181 children had low left ventricular ejection fraction. After adjusting for baseline mortality risk, low left ventricular ejection fraction remained independently associated with mortality (odds ratio, 4.4 [1.0-19.8]; p = 0.0497). Likewise, left ventricular ejection fraction was associated with mortality (odds ratio, 0.96 [0.93-0.99]; p = 0.037) on multivariable analysis for left ventricular ejection fraction less than 65%. Thirty-six percent of 169 children had low global longitudinal strain, and low global longitudinal strain was also independently associated with mortality (odds ratio, 4.6 [1.2-18.0]; p = 0.027).ConclusionsSepsis-associated myocardial dysfunction, whether defined by low left ventricular ejection fraction or low global longitudinal strain, is an independent risk factor for mortality in pediatric septic shock after accounting for the confounding effects of septic shock severity.

Project description:Elevated B-type natriuretic peptide is associated with increased morbidity and mortality in ambulatory patients with congestive heart failure or acute coronary syndromes. Its utility in predicting adverse cardiac surgical outcomes is less certain. We hypothesized that preoperative plasma B-type natriuretic peptide would independently predict in-hospital postoperative ventricular dysfunction, hospital stay, and up to 5-year mortality after primary coronary artery bypass grafting.This is a prospective, longitudinal study of 1023 patients at two institutions undergoing primary coronary artery bypass grafting with cardiopulmonary bypass. Ventricular dysfunction was defined as requirement for at least two inotropes or new intra-aortic balloon pump or ventricular assist device support after coronary artery bypass grafting. Multivariable analyses assessed independent roles of preoperative B-type natriuretic peptide in predicting postoperative ventricular dysfunction, hospital stay, and 5-year all-cause mortality.Preoperative plasma B-type natriuretic peptide concentration predicted ventricular dysfunction, hospital stay, and mortality in univariate and multivariable analyses. Logistic regression demonstrated preoperative B-type natriuretic peptide to independently predict ventricular dysfunction (odds ratio 1.92, 95% confidence interval 1.12-3.29, P = .018), after adjustment for preoperative left ventricular ejection fraction, congestive heart failure severity, and other clinical predictors. Multivariable Cox proportional hazards models showed preoperative B-type natriuretic peptide to independently predict hospital stay (hazard ratio 1.42, 95% confidence interval 1.18-1.72, P = .0002) and mortality (hazard ratio 1.89, 95% confidence interval 1.08-3.33, P = .026).Preoperative plasma B-type natriuretic peptide independently predicted in-hospital ventricular dysfunction, hospital stay, and up to 5-year all-cause mortality after primary coronary artery bypass grafting.

Project description:OBJECTIVES:Sepsis care is becoming a more common target for hospital performance measurement, but few studies have evaluated the acceptability of sepsis or septic shock mortality as a potential performance measure. In the absence of a gold standard to identify septic shock in claims data, we assessed agreement and stability of hospital mortality performance under different case definitions. DESIGN:Retrospective cohort study. SETTING:U.S. acute care hospitals. PATIENTS:Hospitalized with septic shock at admission, identified by either implicit diagnosis criteria (charges for antibiotics, cultures, and vasopressors) or by explicit International Classification of Diseases, 9th revision, codes. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We used hierarchical logistic regression models to determine hospital risk-standardized mortality rates and hospital performance outliers. We assessed agreement in hospital mortality rankings when septic shock cases were identified by either explicit International Classification of Diseases, 9th revision, codes or implicit diagnosis criteria. Kappa statistics and intraclass correlation coefficients were used to assess agreement in hospital risk-standardized mortality and hospital outlier status, respectively. Fifty-six thousand six-hundred seventy-three patients in 308 hospitals fulfilled at least one case definition for septic shock, whereas 19,136 (33.8%) met both the explicit International Classification of Diseases, 9th revision, and implicit septic shock definition. Hospitals varied widely in risk-standardized septic shock mortality (interquartile range of implicit diagnosis mortality: 25.4-33.5%; International Classification of Diseases, 9th revision, diagnosis: 30.2-38.0%). The median absolute difference in hospital ranking between septic shock cohorts defined by International Classification of Diseases, 9th revision, versus implicit criteria was 37 places (interquartile range, 16-70), with an intraclass correlation coefficient of 0.72, p value of less than 0.001; agreement between case definitions for identification of outlier hospitals was moderate (kappa, 0.44 [95% CI, 0.30-0.58]). CONCLUSIONS:Risk-standardized septic shock mortality rates varied considerably between hospitals, suggesting that septic shock is an important performance target. However, efforts to profile hospital performance were sensitive to septic shock case definitions, suggesting that septic shock mortality is not currently ready for widespread use as a hospital quality measure.

Project description:PurposePeripheral differential leukocyte counts are accepted prognostic indicators in patients with acute myocardial infarction (AMI). Herein, we assessed the value of the admission (neutrophil+monocyte)/lymphocyte ratio (NMLR) in predicting in-hospital mortality in these patients.Materials and methodsSamples of patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database meeting the criteria were included. Receiver operating characteristic (ROC) curves were plotted to explore the predictive value and the optimum cut-off value of admission NMLR. Univariate and multivariate Cox regression analyses and restricted cubic spline (RCS) were performed to determine and visualize the association between admission NMLR and in-hospital mortality. The Kaplan-Meier (KM) method was used to plot survival curves of two groups with different admission NMLR levels.ResultsSamples in the non-survival group had higher admission NMLR values than samples in the survival group (12.11 [7.22-21.05] vs. 6.38 [3.96-11.25], P < 0.05). The area under the ROC curve (AUROC) [0.707 (95% Confidence Interval, 0.677-0.737)] was significantly better than those of other indicators related to peripheral differential leukocyte counts, and the optimal cut-off value was 8.518. Cox regression analysis identified that higher admission NMLR was an independent risk factor for in-hospital mortality. RCS visualized the uptrend and the non-linear relationship between admission NMLR and in-hospital mortality (P-value for non-linearity <0.05). The KM survival curve of the high admission NMLR group was significantly lower than that of the low admission NMLR group (P < 0.001), and the former was associated with an increased risk of in-hospital mortality compared to the latter (Hazard Ratio, 1.452; 95% Confidence Interval, 1.132-1.862; P < 0.05).ConclusionAn elevated admission NMLR is an independent predictor for high in-hospital mortality in patients with AMI. And it is superior to other leukocyte-related indexes.

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Anti-NMDA Receptor Autoantibody Is an Independent Predictor of Hospital Mortality but Not Brain Dysfunction in Septic Patients.

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Anti-NMDA Receptor Autoantibody Is an Independent Predictor of Hospital Mortality but Not Brain Dysfunction in Septic Patients.

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