Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury.

Importance: In 2018, the combination of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels became the first US Food and Drug Administration-approved blood test to detect intracranial lesions after mild to moderate traumatic brain injury (MTBI). How this blood test compares with validated clinical decision rules remains unknown. Objectives: To compare the performance of GFAP and UCH-L1 levels vs 3 validated clinical decision rules for detecting traumatic intracranial lesions on computed tomography (CT) in patients with MTBI and to evaluate combining biomarkers with clinical decision rules. Design, Setting, and Participants: This prospective cohort study from a level I trauma center enrolled adults with suspected MTBI presenting within 4 hours of injury. The clinical decision rules included the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), and National Emergency X-Radiography Utilization Study II (NEXUS II) criteria. Emergency physicians prospectively completed data forms for each clinical decision rule before the patients' CT scans. Blood samples for measuring GFAP and UCH-L1 levels were drawn, but laboratory personnel were blinded to clinical results. Of 2274 potential patients screened, 697 met eligibility criteria, 320 declined to participate, and 377 were enrolled. Data were collected from March 16, 2010, to March 5, 2014, and analyzed on August 11, 2021. Main Outcomes and Measures: The presence of acute traumatic intracranial lesions on head CT scan (positive CT finding). Results: Among enrolled patients, 349 (93%) had a CT scan performed and were included in the analysis. The mean (SD) age was 40 (16) years; 230 patients (66%) were men, 314 (90%) had a Glasgow Coma Scale score of 15, and 23 (7%) had positive CT findings. For the CCHR, sensitivity was 100% (95% CI, 82%-100%), specificity was 33% (95% CI, 28%-39%), and negative predictive value (NPV) was 100% (95% CI, 96%-100%). For the NOC, sensitivity was 100% (95% CI, 82%-100%), specificity was 16% (95% CI, 12%-20%), and NPV was 100% (95% CI, 91%-100%). For NEXUS II, sensitivity was 83% (95% CI, 60%-94%), specificity was 52% (95% CI, 47%-58%), and NPV was 98% (95% CI, 94%-99%). For GFAP and UCH-L1 levels combined with cutoffs at 67 and 189 pg/mL, respectively, sensitivity was 100% (95% CI, 82%-100%), specificity was 25% (95% CI, 20%-30%), and NPV was 100%; with cutoffs at 30 and 327 pg/mL, respectively, sensitivity was 91% (95% CI, 70%-98%), specificity was 20% (95% CI, 16%-24%), and NPV was 97%. The area under the receiver operating characteristic curve (AUROC) for GFAP alone was 0.83; for GFAP plus NEXUS II, 0.83; for GFAP plus NOC, 0.85; and for GFAP plus CCHR, 0.88. The AUROC for UCH-L1 alone was 0.72; for UCH-L1 plus NEXUS II, 0.77; for UCH-L1 plus NOC, 0.77; and for UCH-L1 plus CCHR, 0.79. The GFAP biomarker alone (without UCH-L1) contributed the most improvement to the clinical decision rules. Conclusions and Relevance: In this cohort study, the CCHR, the NOC, and GFAP plus UCH-L1 biomarkers had equally high sensitivities, and the CCHR had the highest specificity. However, using different cutoff values reduced both sensitivity and specificity of GFAP plus UCH-L1. Use of GFAP significantly improved the performance of the clinical decision rules, independently of UCH-L1. Together, the CCHR and GFAP had the highest diagnostic performance.

Predicting outcome of patients with severe urinary tract infections admitted via the emergency department.

OBJECTIVE: To evaluate clinical prediction tools for making decisions in patients with severe urinary tract infections (UTIs). METHODS: This was a retrospective study conducted at 2 hospitals (combined emergency department (ED) census 190,000). Study patients were admitted via the ED with acute pyelonephritis or severe sepsis-septic shock related UTI. Area under the receiver operating characteristic curve (AUROC) augmented by decision curve analysis and sensitivity of each rule for predicting mortality and ICU admission were compared. RESULTS: The AUROC of PRACTICE was greater than that of BOMBARD (0.15 difference, 95% confidence interval [CI] = 0.09-0.22), SIRS (0.21 difference, 95% CI = 0.14-0.28) and qSOFA (0.06 difference, 95% CI = 0-0.11) for predicting mortality. PRACTICE had a greater net benefit compared to BOMBARD and SIRS at all thresholds and a greater net benefit compared to qSOFA between a 1% and 10% threshold probability level for predicting mortality. PRACTICE had a greater net benefit compared to all other scores for predicting ICU admission across all threshold probabilities. A PRACTICE score >75 was more sensitive than a qSOFA score >1 (90% versus 54.3%, 35.7 difference, 95% CI = 24.5-46.9), SIRS criteria >1 (18.6 difference, 95% CI = 9.5-27.7), and a BOMBARD score >2 (12.9 difference, 95% CI = 5-12.9) for predicting mortality. CONCLUSION: PRACTICE was more accurate than BOMBARD, SIRS, and qSOFA for predicting mortality. PRACTICE had a superior net benefit at most thresholds compared to other scores for predicting mortality and ICU admissions.

Outcome of Immediate Versus Early Antibiotics in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

STUDY OBJECTIVE: Debate exists about the mortality benefit of administering antibiotics within either 1 or 3 hours of sepsis onset. We performed this meta-analysis to analyze the effect of immediate (0 to 1 hour after onset) versus early (1 to 3 hours after onset) antibiotics on mortality in patients with severe sepsis or septic shock. METHODS: This review was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searched databases included PubMed, EMBASE, Web of Science, and Cochrane Library, as well as gray literature. Included studies were conducted with consecutive adults with severe sepsis or septic shock who received antibiotics within each period and provided mortality data. Data were extracted by 2 independent reviewers and pooled with random effects. Two authors independently assessed quality of evidence across all studies with Cochrane's Grading of Recommendations Assessment, Development and Evaluation methodology and risk of bias within each study, using the Newcastle-Ottawa Scale. RESULTS: Thirteen studies were included: 5 prospective longitudinal and 8 retrospective cohort ones. Three studies (23%) had a high risk of bias (Newcastle-Ottawa Scale). Overall, quality of evidence across all studies (Grading of Recommendations Assessment, Development and Evaluation) was low. Pooling of data (33,863 subjects) showed no difference in mortality between patients receiving antibiotics in immediate versus early periods (odds ratio 1.09; 95% confidence interval 0.98 to 1.21). Analysis of severe sepsis studies (8,595 subjects) found higher mortality in immediate versus early periods (odds ratio 1.29; 95% confidence interval 1.09 to 1.53). CONCLUSION: We found no difference in mortality between immediate and early antibiotics across all patients. Although the quality of evidence across studies was low, these findings do not support a mortality benefit for immediate compared with early antibiotics across all patients with sepsis.

Derivation of a screen to identify severe sepsis and septic shock in the ED-BOMBARD vs. SIRS and qSOFA.

STUDY OBJECTIVE: To predict severe sepsis/septic shock in ED patients. METHODS: We conducted a retrospective case-control study of patients ≥18 admitted to two urban hospitals with a combined ED census of 162,000. Study cases included patients with severe sepsis/septic shock admitted via the ED. Controls comprised admissions without severe sepsis/septic shock. Using multivariate logistic regression, a prediction rule was constructed. The model's AUROC was internally validated using 1000 bootstrap samples. RESULTS: 143 study and 286 control patients were evaluated. Features predictive of severe sepsis/septic shock included: SBP ≤ 110 mm Hg, shock index/SI ≥ 0.86, abnormal mental status or GCS < 15, respirations ≥ 22, temperature ≥ 38C, assisted living facility residency, disabled immunity. Two points were assigned to SI and temperature with other features assigned one point (mnemonic: BOMBARD). BOMBARD was superior to SIRS criteria (AUROC 0.860 vs. 0.798, 0.062 difference, 95% CI 0.022-0.102) and qSOFA scores (0.860 vs. 0.742, 0.118 difference, 95% CI 0.081-0.155) at predicting severe sepsis/septic shock. A BOMBARD score ≥ 3 was more sensitive than SIRS ≥ 2 (74.8% vs. 49%, 25.9% difference, 95% CI 18.7-33.1) and qSOFA ≥ 2 (74.8% vs. 33.6%, 41.2% difference, 95% CI 33.2-49.3) at predicting severe sepsis/septic shock. A BOMBARD score ≥ 3 was superior to SIRS ≥ 2 (76% vs. 45%, 32% difference, 95% CI 10-50) and qSOFA ≥ 2 (76% vs. 29%, 47% difference, 95% CI 25-63) at predicting sepsis mortality. CONCLUSION: BOMBARD was more accurate than SIRS and qSOFA at predicting severe sepsis/septic shock and sepsis mortality.

Acute appendicitis presenting as acute gastritis in an adult patient with undiagnosed congenital gut malrotation: a case report.

BACKGROUND: We report a case of an atypical presentation of acute appendicitis in an adult due to an undiagnosed congenital gut malrotation. OBJECTIVE: The obvious benefit of observation with serial examinations followed by the use of computed tomography (CT) is discussed in aiding in the diagnosis for atypical presentations of appendicitis. CASE REPORT: A 45-year-old man who presented with epigastric pain and vomiting was diagnosed with acute left-sided appendicitis on CT scan. The patient's appendix was located in the left lower quadrant of the abdomen due to undiagnosed congenital gut malrotation, thus resulting in an atypical presentation of a common illness. CONCLUSION: Observation with serial examinations, followed by CT scanning if indicated, is an invaluable strategy to use in diagnosing atypical presentations of common pathology.

Unintentional ingestion of potassium permanganate.

This case of an unintentional ingestion of an unknown amount of potassium permanganate by a 5-year-old boy, and its sequelae, exemplifies the potential danger of this poison. Due to the wide availability of this agent in over-the-counter preparations and the high potential for serious sequelae, clinicians should be aware of the actions of this agent, as well as the diagnostic and management features associated with it.