Inter-rater reliability and prognostic value of baseline Radiographic Assessment of Lung Edema (RALE) scores in observational cohort studies of inpatients with COVID-19.

OBJECTIVES: To reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes. SETTING: Hospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems. PARTICIPANTS: 425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set. PRIMARY AND SECONDARY OUTCOMES: We measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host-response biomarkers, SARS-CoV-2 RNA load and clinical outcomes. RESULTS: Inter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). In the discovery cohort, the required level of respiratory support at the time of CXR acquisition (supplemental oxygen or non-invasive ventilation (n=178); invasive-mechanical ventilation (n=234), extracorporeal membrane oxygenation (n=13)) was significantly associated with RALE scores (median (IQR): 20.0 (14.1-26.7), 26.0 (20.5-34.0) and 44.5 (34.5-48.0), respectively, p<0.0001). Among invasively ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, soluble receptor of advanced glycation end-products and soluble tumour necrosis factor receptor 1 (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted HR 1.04 (1.02-1.07), p=0.002). We replicated the significant associations of RALE scores with baseline disease severity and mortality in the independent validation data set. CONCLUSIONS: With a reproducible method to measure radiographic severity in COVID-19, we found significant associations with clinical and physiologic severity, host inflammation and clinical outcomes. The incorporation of radiographic severity assessments in clinical decision-making may provide important guidance for prognostication and treatment allocation in COVID-19.

Ketogenic-Diet Shake Containing Uncaria tomentosa-Associated Acute Interstitial Nephritis.

Uncaria tomentosa is a plant that has been used in traditional medicine for its anti-inflammatory, immunomodulatory, and immunostimulant properties. As a result, it can be found in several over-the-counter supplements worldwide. Acute interstitial nephritis (AIN) can be due to an offending medication, infection, or autoimmunity. We present a case of a patient who was on a strict ketogenic diet, utilizing over-the-counter diet shakes containing the herbal supplement Uncaria tomentosa who developed acute kidney injury with a serum creatinine of 3.6 mg/dL up from a baseline of 0.7 mg/dL. Serological evaluation was negative, and kidney biopsy revealed interstitial inflammatory infiltrates including focally prominent eosinophils and multifocal tubulitis. Stopping the keto-diet shake containing Uncaria tomentosa and concomitant corticosteroid therapy resulted in improvement in kidney function to near baseline. To our knowledge, this is the only biopsy-proven case of AIN in the setting of Uncaria tomentosa use.

Efficacy of Coronary Computed Tomography Angiography Versus Nuclear Perfusion Stress in Preventing Downstream Imaging and Prolonged Inpatient Length of Stay in Low to Medium Risk Patients With Chest Pain.

Background  The first-line imaging for low to medium-risk patients presenting to the emergency department with stable chest pain is often a matter of debate. Chest pain is the second most common presentation to the emergency department. Non-invasive imaging has been useful in assisting in the diagnosis of coronary artery disease.  Aim  The aim of this study is to compare outcomes of Single Photon Emission Computed Tomography (SPECT) Nuclear Perfusion Stress and Coronary Computed Tomography Angiography (CCTA) performed in low to medium-risk patients and how they led to prolonged hospitalization and downstream testing. Materials and methods A total of 519 patients were selected for chart review using the following criteria: admitted for chest pain and older than 18 years of age. Those who presented with STEMI (ST-Elevation Myocardial Infarction) or non-(N)STEMI were excluded. Among these patients, four patients were excluded since their initial test was neither a CCTA nor SPECT Nuclear (NM) Perfusion Stress test. Another 30 patients were excluded based on HEART score (a clinical tool to stratify the risk of major adverse cardiac events) >7 and 111 patients with estimated glomerular filtration rate (eGFR) <60 were excluded. A total of 374 patients underwent analysis. Results Univariate data analysis of 374 patients demonstrated a higher percentage of patients with HEART scores 0-3 underwent CCTA (51.6% vs. 31.8% p=0.0250) when compared to patients with SPECT NM perfusion. Multivariable logistic regression revealed that the difference in length of stay between SPECT NM perfusion stress and CCTA was significant, patients with the CCTA test were less likely to have a length of stay ≥24 hours (odds ratio {OR}=0.41, p=0.0465) compared to patients with NM perfusion stress test. Conclusion This retrospective cohort study demonstrated that patients who underwent CCTA upon chest pain admission were more likely to have a decreased length of stay time to less than 24 hours.

Radiographic Assessment of Lung Edema (RALE) Scores are Highly Reproducible and Prognostic of Clinical Outcomes for Inpatients with COVID-19.

INTRODUCTION: Chest imaging is necessary for diagnosis of COVID-19 pneumonia, but current risk stratification tools do not consider radiographic severity. We quantified radiographic heterogeneity among inpatients with COVID-19 with the Radiographic Assessment of Lung Edema (RALE) score on Chest X-rays (CXRs). METHODS: We performed independent RALE scoring by ≥2 reviewers on baseline CXRs from 425 inpatients with COVID-19 (discovery dataset), we recorded clinical variables and outcomes, and measured plasma host-response biomarkers and SARS-CoV-2 RNA load from subjects with available biospecimens. RESULTS: We found excellent inter-rater agreement for RALE scores (intraclass correlation co-efficient=0.93). The required level of respiratory support at the time of baseline CXRs (supplemental oxygen or non-invasive ventilation [n=178]; invasive-mechanical ventilation [n=234], extracorporeal membrane oxygenation [n=13]) was significantly associated with RALE scores (median [interquartile range]: 20.0[14.1-26.7], 26.0[20.5-34.0] and 44.5[34.5-48.0], respectively, p<0.0001). Among invasively-ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, sRAGE and TNFR1 levels (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.04[1.02-1.07], p=0.002). We validated significant associations of RALE scores with baseline severity and mortality in an independent dataset of 415 COVID-19 inpatients. CONCLUSION: Reproducible assessment of radiographic severity revealed significant associations with clinical and physiologic severity, host-response biomarkers and clinical outcome in COVID-19 pneumonia. Incorporation of radiographic severity assessments may provide prognostic and treatment allocation guidance in patients hospitalized with COVID-19.

The Cleveland Clinic Kidney Biopsy Epidemiological Project.

Background: The kidney biopsy is the gold standard for diagnosing glomerular diseases. Large-scale, epidemiologic studies describing the prevalence of kidney diseases are lacking, especially in the United States. We aimed to determine the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise. Methods: We identified all patients with a native kidney biopsy performed or reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, sex, race, and location to determine epidemiologic trends. Results: Of >9600 patients, we excluded transplant and donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46% female patients. Self-reported racial demographics included 73% White, 22% Black, 3% multiracial, and 2% Asian background, with 5% Hispanic. Common diagnoses were: FSGS (n=633, 15%), diabetic kidney disease (DKD) (n=602, 15%), IgA nephropathy (n=319, 8%), lupus nephritis (LN) (n=289, 7%), pauci-immune glomerulonephritis (n=275, 7%), membranous nephropathy (n=211, 5%), and amyloidosis (n=110, 3%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those aged >70 years were more likely to have FSGS, whereas those <45 years were more likely to have IgA nephropathy or LN. Males were more likely to have FSGS or IgAN, and less likely to have LN. Black patients were more likely to have FSGS, DKD, or LN. Hispanic patients were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum before and during the COVID-19 pandemic. Conclusion: Our study catalogs the spectrum of biopsy-proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials, and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States.

A Study to Assess the Factors Affecting Adherence to Exercise in the Indian Population.

Introduction As proven by many previous studies, physical inactivity is associated with many diseases, including heart conditions and cancer. The elimination of physical inactivity helps increase life expectancy and reduce morbidity. Nonadherence to exercise is a common problem faced by many people. The goal of this study was to determine the percentage of people in the Indian population who regularly exercise. We also assessed factors for nonadherence, motivating factors, and the intensity of exercise usually performed and explored any association between adherence to exercise and demographic factors. Materials and methods We conducted an anonymous questionnaire-based, cross-sectional study in an adult Indian population (participants were older than 18 years) from rural and urban areas having no contraindication to at least some form of voluntary exercise. Data were collected via email by sending a questionnaire, and an appropriate statistical methodology was used to derive the results. Results This study included 220 individuals older than 18 years, and most participants were aged 25 to 30 years (35.5%). Most participants (67.3%) were women, and 32.7% were men. Forty-one percent of the total population reported suffering from some medical condition. Nearly half (51.8%) of the subjects were involved in physical activity, and 48.2% were not involved in physical activity. The most common reason for not exercising was a lack of time followed by a lack of motivation. Maintenance of good health was the main reported benefit of physical exercise, with self-motivation being the main motivator. Low-intensity exercise was the preferred form of exercise for most of the participants; high-intensity exercise was preferred by younger participants, though less commonly than low-intensity exercise. Older participants (i.e., those aged > 40 years) preferred moderate-intensity exercise. Only half the study population were educated regarding physical activity by a healthcare professional. We found no statistically significant association between the presence of a medical condition, body mass index (BMI), or healthcare education and adherence to exercise. Conclusion The inclusion of exercise in a daily routine is one of the more important lifestyle changes advised for all ailments and for improvements in patient quality of life. Nearly half the Indian population does not exercise daily. Because we found no statistical significance between demographic factors, health conditions, BMI, or general healthcare education, an individualized education and exercise plan may help improve exercise adherence.