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.

Milk-Alkali Syndrome: How Electronic Medical Record Open Notes Helped to Rule Out Cancer.

BACKGROUND Milk-alkali syndrome is caused by excessive consumption of calcium and absorbable alkali and typically presents as a triad of hypercalcemia, acute renal failure, and metabolic alkalosis. In the era of histamine receptor blockers and proton pump inhibitors, the incidence of milk-alkali syndrome has decreased. However, the disease has not been eliminated, due to existing calcium-containing therapies. Here, we present a case of severe milk-alkali syndrome with a challenging initial diagnosis. CASE REPORT We present the case of a 64-year-old man who came to the hospital with encephalopathy. Serologic evaluation revealed acute renal failure, severe hypercalcemia, and metabolic alkalosis. He underwent volume resuscitation, with the initiation of calcitonin. Despite our efforts, the patient developed anuria and proceeded to intermittent hemodialysis. His workup was unrevealing, including an appropriately suppressed parathyroid hormone level, low vitamin D, and normal serum protein electrophoresis and angiotensin converting enzyme levels. Considering his persistent encephalopathy, the team was unable to obtain information from the patient regarding his calcium intake. However, at home, the patient's significant other read his progress notes in the electronic medical record and reported that he consumed at least 1 bottle of calcium carbonate (Tums) every week. Once the encephalopathy resolved, the patient confirmed this information. CONCLUSIONS The search for malignancy in the setting of hypercalcemia was ceased because of the family's at-home electronic medical record use and reporting of Tums overuse. Milk-alkali syndrome, although a rarity, should not be forgotten as a cause of hypercalcemia.

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.

A Bite So Bad: Septic Shock Due to Capnocytophaga Canimorsus Following a Dog Bite.

Infection by Capnocytophaga canimorsus (C. canimorsus), a Gram-negative rod found in the normal oral flora of canine and feline species and transmitted through bites or scratches, is a rare phenomenon. Infections most commonly occur in alcoholics and immunocompromised patients. In this report, we describe the case of a middle-aged male with a history of alcohol abuse who presented with septic shock and multisystem organ failure following a suspected dog bite. The patient was a 59-year-old Caucasian male with alcohol abuse disorder who initially presented with encephalopathy and lethargy. The patient had scratches and multiple healing wounds, with a mottled appearance on his extremities. According to his wife, the patient had been playing aggressively with his dog at home. On admission, he was febrile, tachycardic, and saturating in the 80s on ambient air. His extremities rapidly developed diffuse purpura and dry gangrene of all digits along with the tip of his nose and genitals. The patient developed septic shock and multisystem organ failure. Blood cultures initially grew Gram-positive cocci and Gram-negative rods for which broad-spectrum antibiotics were initiated. Follow-up blood cultures were positive for C. canimorsus and the antibiotic regimen was adjusted accordingly. His condition continued to deteriorate. His family opted for comfort measures only and he died soon after. Common sequelae of C. canimorsus infection include septic shock with multisystem organ failure, disseminated purpuric lesions, hypotension, encephalopathy, and acute renal failure. As seen in our patient, C. canimorsus infection should be considered in such patients, particularly if there is a recent history of an animal bite. Prompt initiation of appropriate treatment is essential to improve patient prognosis.

Grit in Medical Education: Differing Perspectives of Residents and Mentors.

Background Increasing concerns about depression and burnout in residents have led to a recent focus on assessing "non-cognitive" traits in residents and residency applicants. One attribute that has received significant attention is grit, defined as trait-level perseverance and passion for long-term goals. With an objective measure available, an important question is under what circumstances of administration is that measure reliable and accurate. The goal of this study was to ascertain whether internal medicine residents and their faculty mentors were congruent in their ratings of resident grit, or if not, how the ratings differed.  Methods Subjects were internal medicine residents (N=42) at a community-based university-affiliated hospital internal medicine residency program. Near the end of the academic year 2019, residents completed the GRIT-S (short form). As each resident is assigned a mentor during their training, each resident's mentor was also asked to complete the GRIT-S based on their view of their mentee.  Results This study failed to find a significant correlation between resident self-ratings of grit and those of their mentors. Conclusions The results of these two studies underscore the difficulty in obtaining accurate assessments of non-cognitive traits. These results further the understanding of the role of grit and raise important questions about how assessments might be used to assure validity. Further areas of inquiry into this potentially important characteristic are suggested.