Analysis of Protein Biomarkers From Hospitalized COVID-19 Patients Reveals Severity-Specific Signatures and Two Distinct Latent Profiles With Differential Responses to Corticosteroids.

OBJECTIVES: To identify and validate novel COVID-19 subphenotypes with potential heterogenous treatment effects (HTEs) using electronic health record (EHR) data and 33 unique biomarkers. DESIGN: Retrospective cohort study of adults presenting for acute care, with analysis of biomarkers from residual blood collected during routine clinical care. Latent profile analysis (LPA) of biomarker and EHR data identified subphenotypes of COVID-19 inpatients, which were validated using a separate cohort of patients. HTE for glucocorticoid use among subphenotypes was evaluated using both an adjusted logistic regression model and propensity matching analysis for in-hospital mortality. SETTING: Emergency departments from four medical centers. PATIENTS: Patients diagnosed with COVID-19 based on International Classification of Diseases , 10th Revision codes and laboratory test results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Biomarker levels generally paralleled illness severity, with higher levels among more severely ill patients. LPA of 522 COVID-19 inpatients from three sites identified two profiles: profile 1 ( n = 332), with higher levels of albumin and bicarbonate, and profile 2 ( n = 190), with higher inflammatory markers. Profile 2 patients had higher median length of stay (7.4 vs 4.1 d; p < 0.001) and in-hospital mortality compared with profile 1 patients (25.8% vs 4.8%; p < 0.001). These were validated in a separate, single-site cohort ( n = 192), which demonstrated similar outcome differences. HTE was observed ( p = 0.03), with glucocorticoid treatment associated with increased mortality for profile 1 patients (odds ratio = 4.54). CONCLUSIONS: In this multicenter study combining EHR data with research biomarker analysis of patients with COVID-19, we identified novel profiles with divergent clinical outcomes and differential treatment responses.

Persistent Hiccups after Subthalamic Nucleus Deep Brain Stimulator Implantation for Parkinson's Disease: Case Report and Literature Review.

Hiccups are mediated by a reflex arc that consists of afferent, central, and efferent components. The structures involved in the central component have not been fully elucidated, although several brainstem structures have been implicated, including the subthalamic nucleus (STN). Accordingly, Parkinson's disease (PD), a disease defined by the loss of dopaminergic neurons in the STN, has an interesting, although unspecified, relationship to hiccups. Hiccups have been described in association with PD and the use of dopaminergic medications. Interestingly, deep brain stimulation (DBS) of the STN appears to be implicated in the pathogenesis of hiccups as well. There have been sporadic reports of hiccups occurring in conjunction with STN-DBS. We present a case of hiccups occurring after STN-DBS for PD in a 65-year-old man. STN-DBS significantly improved his PD symptoms; however, he developed persistent and daily hiccups. As of writing, 24 months after surgery, the patient experiences hiccups several times per day with no associated gastrointestinal complaints and with significant improvement in his PD symptoms. This report describes the case details and summarizes the existing literature describing hiccups in patients undergoing surgical treatment for PD.