Early Cardiac Evaluation, Abnormal Test Results, and Associations with Outcomes in Patients with Acute Brain Injury Admitted to a Neurocritical Care Unit.

Background: to examine factors associated with cardiac evaluation and associations between cardiac test abnormalities and clinical outcomes in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), spontaneous subarachnoid hemorrhage (SAH), spontaneous intracerebral hemorrhage (sICH), and traumatic brain injury (TBI) requiring neurocritical care. Methods: In a cohort of patients ≥18 years, we examined the utilization of electrocardiography (ECG), beta-natriuretic peptide (BNP), cardiac troponin (cTnI), and transthoracic echocardiography (TTE). We investigated the association between cTnI, BNP, sex-adjusted prolonged QTc interval, low ejection fraction (EF < 40%), all-cause mortality, death by neurologic criteria (DNC), transition to comfort measures only (CMO), and hospital discharge to home using univariable and multivariable analysis (adjusted for age, sex, race/ethnicity, insurance carrier, pre-admission cardiac disorder, ABI type, admission Glasgow Coma Scale Score, mechanical ventilation, and intracranial pressure [ICP] monitoring). Results: The final sample comprised 11,822 patients: AIS (46.7%), sICH (18.5%), SAH (14.8%), and TBI (20.0%). A total of 63% (n = 7472) received cardiac workup, which increased over nine years (p < 0.001). A cardiac investigation was associated with increased age, male sex (aOR 1.16 [1.07, 1.27]), non-white ethnicity (aOR), non-commercial insurance (aOR 1.21 [1.09, 1.33]), pre-admission cardiac disorder (aOR 1.21 [1.09, 1.34]), mechanical ventilation (aOR1.78 [1.57, 2.02]) and ICP monitoring (aOR1.68 [1.49, 1.89]). Compared to AIS, sICH (aOR 0.25 [0.22, 0.29]), SAH (aOR 0.36 [0.30, 0.43]), and TBI (aOR 0.19 [0.17, 0.24]) patients were less likely to receive cardiac investigation. Patients with troponin 25th-50th quartile (aOR 1.65 [1.10-2.47]), troponin 50th-75th quartile (aOR 1.79 [1.22-2.63]), troponin >75th quartile (aOR 2.18 [1.49-3.17]), BNP 50th-75th quartile (aOR 2.86 [1.28-6.40]), BNP >75th quartile (aOR 4.54 [2.09-9.85]), prolonged QTc (aOR 3.41 [2.28; 5.30]), and EF < 40% (aOR 2.47 [1.07; 5.14]) were more likely to be DNC. Patients with troponin 50th-75th quartile (aOR 1.77 [1.14-2.73]), troponin >75th quartile (aOR 1.81 [1.18-2.78]), and prolonged QTc (aOR 1.71 [1.39; 2.12]) were more likely to be associated with a transition to CMO. Patients with prolonged QTc (aOR 0.66 [0.58; 0.76]) were less likely to be discharged home. Conclusions: This large, single-center study demonstrates low rates of cardiac evaluations in TBI, SAH, and sICH compared to AIS. However, there are strong associations between electrocardiography, biomarkers of cardiac injury and heart failure, and echocardiography findings on clinical outcomes in patients with ABI. Findings need validation in a multicenter cohort.

Broad-spectrum monoclonal antibodies against chikungunya virus structural proteins: Promising candidates for antibody-based rapid diagnostic test development.

In response to the aggressive global spread of the mosquito-borne chikungunya virus (CHIKV), an accurate and accessible diagnostic tool is of high importance. CHIKV, an arthritogenic alphavirus, comprises three genotypes: East/Central/South African (ECSA), West African (WA), and Asian. A previous rapid immunochromatographic (IC) test detecting CHIKV E1 protein showed promising performance for detection of the ECSA genotype. Unfortunately, this kit exhibited lower capacity for detection of the Asian genotype, currently in circulation in the Americas, reflecting the low avidity of one of the monoclonal antibodies (mAbs) in this IC kit for the E1 protein of the Asian-genotype because of a variant amino acid sequence. To address this shortcoming, we set out to generate a new panel of broad-spectrum mouse anti-CHIKV mAbs using hybridoma technology. We report here the successful generation of mouse anti-CHIKV mAbs targeting CHIKV E1 and capsid proteins. These mAbs possessed broad reactivity to all three CHIKV genotypes, while most of the mAbs lacked cross-reactivity towards Sindbis, dengue, and Zika viruses. Two of the mAbs also lacked cross-reactivity towards other alphaviruses, including O'nyong-nyong, Ross River, Mayaro, Western Equine Encephalitis, Eastern Equine Encephalitis, and Venezuelan Equine Encephalitis viruses. In addition, another two mAbs cross-reacted weakly only with most closely related O'nyong-nyong virus. Effective diagnosis is one of the keys to disease control but to date, no antibody-based rapid IC platform for CHIKV is commercially available. Thus, the application of the mAbs characterized here in the rapid diagnostic IC kit for CHIKV detection is expected to be of great value for clinical diagnosis and surveillance purposes.