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.

Accuracy of Noninvasive Fibrosis Scores to Detect Advanced Fibrosis in Patients With Type-2 Diabetes With Biopsy-proven Nonalcoholic Fatty Liver Disease.

BACKGROUND: Recent guidelines have recommended screening for nonalcoholic fatty liver disease (NAFLD) and case finding of advanced disease with fibrosis in patients with type-2 diabetes (T2D). The aim of this study is to assess the accuracy of commonly used noninvasive scores to predict the presence of advanced fibrosis (AF) in a large cohort of diabetics in real-life settings. PATIENTS AND METHODS: Using International Classification of Diseases, Ninth Revision (ICD-9) codes, all patients with the diagnosis of T2D who had a liver biopsy for suspected NAFLD between January 2000 and December 2015, were identified and analyzed. Patients with secondary causes of hepatic steatosis were excluded. AST/ALT ratio, aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4) index, and Nonalcoholic fatty liver disease Fibrosis Score (NFS) were calculated to predict advanced disease. Sensitivity, specificity, and area under the receiver operator curve were calculated and compared with liver biopsies to predict the overall accuracy of each score. RESULTS: A total of 1319 patients with T2D underwent liver biopsy for suspected NAFLD. After exclusions, 1,157 subjects were included in the final analysis. Our cohort consisted of 64.6% females and 88.4% were whites. Overall, 85% of the population was overweight or obese (body mass index>25 kg/m). Liver biopsy showed 31.7% with AF [Nonalcoholic Steatohepatitis Clinical Research Network (NASH-CRN) stage 3 to 4]. In comparison to liver biopsy, for the diagnosis of AF, AST/ALT>1.4, APRI>1.5, FIB-4>2.67, and NFS>0.676 had reasonable specificities of 84.2%, 97.4%, 69.9%, and 93% but poor sensitivities of 27.4%, 16.5%, 6.7%, and 44.1%, respectively. Even at lower cutoff values of AST/ALT≥1, APRI≥1, and FIB-4≥1.45 sensitivities remained low at 60.7%, 27.9%, and 72.6%, respectively, except for NFS ≥-1.455 with sensitivity of 94.6%, but at this cutoff, its specificity decreased to 16.9%. The area under the receiver operator curve to detect AF was 0.62, 0.74, 0.77, and 0.72, respectively. CONCLUSIONS: In this large cohort of adult patients with T2D and NAFLD, commonly used fibrosis scores had reasonable specificity, but poor sensitivity for detecting AF in diabetics. The development of reliable biomarkers for NAFLD/NASH in diabetics is urgently needed.

Obesity Is Associated with Decreased Risk of Clostridium difficile Infection in Hospitalized Patients with Pouchitis.

BACKGROUND: Clostridium difficile infection (CDI) is one of the leading causes of health-care-associated infections in the USA. There are limited data available regarding CDI in hospitalized patients with inflammatory bowel disease-related ileal pouch. AIMS: This study aimed to evaluate the demographics, clinical features, risk factors, and admission outcomes among hospitalized patients with CDI-related pouchitis (CDP). METHODS: Retrospective chart review was performed for patients who were admitted to our institute for pouchitis between 2013 and 2016 to identify patients with CDP. Logistic regression analysis was performed to assess the risk factors associated with CDP. RESULTS: A total of 160 subjects with pouchitis had a total of 218 admissions during the study period. Primary admission diagnosis was pouchitis or inflammatory bowel disease flare-up for 202 (93%) admissions. Clostridium difficile was tested at least once for 72 patients, and the diagnosis of CDP was established for 16 (10%) patients. All patients with CDP were symptomatic, 13 (81%) had diarrhea, 8 (50%) had abdominal pain, 7 (44%) had nausea/vomiting, and 2 (13%) had gastrointestinal bleeding. On multivariable analysis, only body mass index > 25 (OR 0.25, 95% CI 0.06-0.94, p = 0.048) was significantly associated with decreased risk of CDP. No patients in CDP cohort were admitted to ICU, died at the hospital, or readmitted in 30 days after the discharge. CONCLUSIONS: In our cohort, obesity was associated with low risk of CDP among hospitalized patients with pouchitis. This finding warrants further validation in prospective studies.

A Human Case of an Infection by the Pathogenic Streptococci that Causes "Strangles" in Horses.

Strangles is a contagious upper respiratory tract infection primarily affecting equines. It is rare disease with zoonotic transmission. It is caused by the bacterium, Streptococcus equi. We present the rare case of strangles in an elderly patient complicated by bacteraemia, osteomyelitis and native valve endocarditis. The patient was treated successfully with appropriate antibiotics and no surgical intervention was needed. In an age of accelerated emerging zoonosis, this is an important entity clinicians should be aware of to prevent delay in diagnosis and poor outcome. LEARNING POINTS: Strangles is a disease of equines, rarely it can affect the humans and can delay the diagnosis and management.This case represents the importance of thorough history taking and assessment.Use of an appropriate antibiotics can avoid surgical interventions in the some cases of Strangles.

A Rare Case of Spontaneous Intussusception in an Elderly Patient.

Intussusception is an uncommon pathology in the adult population. Most intussusception cases result from an underlying pathological lead point, oftentimes a malignant neoplasm. We report a case of intussusception in an adult male patient who presented with abdominal pain and currant jelly diarrhea. The patient underwent laparoscopic right hemicolectomy and the biopsy of the affected colon did not show any pathological lead point. Intussusception remains an important differential diagnosis in patients presenting with abdominal pain and bloody diarrhea.

Angiotensin Receptor Blockers Associated Enteropathy-Brief Report.

The current literature has shown equivocal results regarding the association of Olmesartan and other angiotensin receptor blockers (ARBs) use and the presence of Celiac sprue-like enteropathy (CSLE). Various factors affecting the association are- patient population under study, geographic area, and duration of use of medication. Various case reports/case series and observational studies have shown the mixed results regarding an association. We have tried to answer a question what exists in the literature regarding the angiotensin receptor blockers related sprue like enteropathy.

Gastrointestinal pathophysiology of SARS-CoV2 - a literature review.

SARS-CoV2 is a novel coronavirus responsible for causing COVID-19, first identified in the city of Wuhan, China and officially declared a pandemic by the World Health Organization. SARS-CoV2 expresses high affinity to human ACE2 receptors, including within the gastrointestinal tract. Patients with COVID-19 exhibit a wide spectrum of GI symptoms including anorexia, nausea, vomiting, abdominal pain, and abnormal liver function tests. Pathogenesis behind gastrointestinal symptoms caused by SARS-CoV2 has been postulated to be multifactorial including disruption of the intestinal mechanical barrier integrity, alteration of the gut microbiome and systemic inflammatory response to the virus. SARS-CoV-2 RNA has also been found in stool samples of infected patients for a significantly longer period than in nasopharyngeal samples, though the implication of this finding is unclear at this time. Liver injury in patients with COVID-19 is usually mild, stemming from immune-mediated damage, drug induced hepatotoxicity, or ischemia from sepsis. Patients with pre-existing liver disease may be at a higher risk for hospitalization and mortality. Given the high degree of infectivity of this disease, healthcare providers will need to remain watchful for resurgence of this virus. Strict protocols should be implemented regarding hand hygiene, isolation, personal protective equipment, and appropriate disposal of waste. It is also imperative to identify patients with gastrointestinal symptoms at an early stage as these patients may have a prolonged course between symptom onset and viral clearance.

Prevalence and Predictors of Gastrointestinal Dysmotility in Patients with Hypermobile Ehlers-Danlos Syndrome: A Tertiary Care Center Experience.

Introduction Ehlers-Danlos syndrome (EDS), specifically the hypermobility type (hEDS), is associated with a variety of gastrointestinal (GI) conditions. This study aims to evaluate the prevalence of and factors associated with gut dysmotility in patients with hEDS. Methods This is a retrospective study of hEDS patients conducted at the Cleveland Clinic's Center for Personalized Genetic Healthcare between January 2007 and December 2017. Demographics, GI motility testing, endoscopic, and imaging data were extracted from the patients' charts. Results A total of 218 patients with hEDS were identified. Among them, 136 (62.3%) patients had at least one GI symptom at the time of EDS diagnosis. Motility testing was performed and reported in 42 (19.2%) patients. Out of them, five (11.9%) had esophageal dysmotility, 18 (42.8%) had gastroparesis, five (11.9%) had small bowel/colon altered transit time, and four (9.5%) had global dysmotility. In univariable analysis, patients with postural orthostatic tachycardia syndrome (POTS) [odds ratio (OR): 8.88, 95% CI: 3.69-24.9, p<0.0001], fibromyalgia (OR: 4.43, 95% CI: 2.04-10.1, p=0.0002), history of irritable bowel syndrome (OR: 5.01, 95% CI: 2.31-11.2, p<0.0001), and gastroesophageal reflux disease (OR: 3.33, 95% CI: 1.55-7.44, p=0.002) were more likely to be diagnosed with GI dysmotility. On multivariable analysis, only POTS (OR: 5.74, 95% CI: 2.25-16.7, p=0.0005) was significantly associated with an increased likelihood of GI dysmotility. Conclusions This study suggests that GI symptoms are relatively common among patients with hEDS. Of the patients tested for dysmotility, 76.2% were found to have some form of dysmotility. POTS was found to be an independent predictive factor for GI dysmotility.

Interventions to Decrease Overuse of Cardiac Monitoring (Telemetry) When Transitioning from the Intensive Care Unit to the Regular Nursing Floor.

Background Cardiac monitoring (telemetry) is a common over-utilized hospital resource in the United States. Previous studies have shown that telemetry does not improve outcomes for low-risk patients. Inappropriate utilization occurs because of lack of awareness of guideline-based indications or non-adherence to known indications. Objective A quality improvement study was conducted to reduce telemetry overutilization during the transition of care from the intensive care unit (ICU) by 15% through increasing awareness of indications for telemetry. Methods The study cohort included patients originally admitted to the ICU for sepsis who had improved and were stable for transfer to a non-ICU setting. Subjects were identified and included during pre-intervention (six weeks) and intervention (six weeks) periods. Resident physicians and nurse practitioners were targeted using multiple modalities of education: didactic lectures during week one, poster demonstrations during week three, and video presentations during week five. Results A total of 246 study subjects during the pre-intervention and 94 study subjects in the intervention period were studied; 187 of the 246 subjects in the pre-intervention arm (76%) and 58 of the 94 subjects in the intervention arm (61.7%) were transferred with telemetry. Telemetry utilization dropped by 23.1% at the end of the intervention period. Conclusion Educating the caregivers about the indications for telemetry led to a decrease in over-utilization of telemetry on the transition of care from the ICU to the regular nursing floor. Repetitive and multi-modality educational interventions were effective tools and associated with increased adherence to established guidelines for telemetry usage.

Serotonin syndrome in patients with peripheral neuropathy: a diagnostic challenge.

According to the Hunter Serotonin Toxicity Criteria, the presence of either clonus or hyperreflexia is a must for making a diagnosis of serotonin syndrome (SS). We report five patients with SS who had areflexia because of associated polyneuropathy. None of the patients fulfilled the Hunter criteria for SS. However, all five patients had features suggestive of neuromuscular hyperactivity, autonomic hyperactivity and altered mental status and fulfilled the Sternbach criteria for SS. All patients responded to cyproheptadine within 5 days to 2 weeks duration. These cases highlight the limitations of the Hunter criteria for SS in patients with associated polyneuropathy.