Is rapid acute coronary syndrome evaluation with high-sensitivity cardiac troponin less costly? An economic evaluation.

Objective: Protocols to evaluate for myocardial infarction (MI) using high-sensitivity cardiac troponin (hs-cTn) have the potential to drive costs upward due to the added sensitivity. We performed an economic evaluation of an accelerated protocol (AP) to evaluate for MI using hs-cTn to identify changes in costs of treatment and length of stay compared with conventional testing. Methods: We performed a planned secondary economic analysis of a large, cluster randomized trial across nine emergency departments (EDs) from July 2020 to April 2021. Patients were included if they were 18 years or older with clinical suspicion for MI. In the AP, patients could be discharged without further testing at 0 h if they had a hs-cTnI < 4 ng/L and at 1 h if the initial value were 4 ng/L and the 1-h value ≤7 ng/L. Patients in the standard of care (SC) protocol used conventional cTn testing at 0 and 3 h. The primary outcome was the total cost of treatment, and the secondary outcome was ED length of stay. Results: Among 32,450 included patients, an AP had no significant differences in cost (+$89, CI: -$714, $893 hospital cost, +$362, CI: -$414, $1138 health system cost) or ED length of stay (+46, CI: -28, 120 min) compared with the SC protocol. In lower acuity, free-standing EDs, patients under the AP experienced shorter length of stay (-37 min, CI: -62, 12 min) and reduced health system cost (-$112, CI: -$250, $25). Conclusion: Overall, the implementation of AP using hs-cTn does not result in higher costs.

The use of percutaneous left atrial appendage occluder device in a patient with prior surgical ligation with incomplete exclusion: a case report.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and the most common cause of cardioembolic stroke. The left atrial appendage (LAA) is the main source of thrombus formation in patients with AF. Therapies include use of percutaneous LAA closure devices, or surgical LAA occlusion (LAAO). Despite these options, complete closure of the LAA is not always achieved, and residual communication between the LAA and atrium may result in increased thrombus formation. Although studies have analysed the use of percutaneous measures such as coils, plugs, or second occluder device deployment in LAA with peri-device leak (PDL), use of percutaneous occlude devices in surgically occluded LAA is far less studied. Case summary: We present a case of a 79-year-old female patient who underwent LAAO device deployment within a surgically occluded LAA with PDL. She underwent 27 mm LAAO device (WATCHMANTM) deployment and all the P.A.S.S. (Position, Anchor, Size, and Seal) criteria were satisfied. Only 1.4 mm PDL was present. She was continued on apixaban and aspirin post-operatively. Post-operative transoesophageal echocardiogram at 6 weeks demonstrated trivial PDL measuring 1.49 mm. Patient was continued on aspirin and clopidogrel, with discontinuation of apixaban. Discussion: Percutaneous LAAO device deployment in previously surgically ligated LAA with incomplete exclusion is a potential therapeutic option for patients with AF and a high bleeding risk seeking a minimally invasive strategy, in an attempt to de-escalate anticoagulation therapy.

Outcomes in patients with sarcoidosis and COVID-19.

BACKGROUND AND AIM: The effect of COVID-19 in patients with sarcoidosis has not been fully explored. The aim was to conduct a retrospective cohort study investigating outcomes in patients with sarcoidosis who were hospitalized with COVID-19. METHODS: We included patients who had diagnoses of sarcoidosis and COVID-19 between January 1, 2020, and February 28, 2021. Primary outcomes included development of critical COVID-19; need for supplemental oxygen, noninvasive ventilation, and invasive ventilation; and death. Association of comorbidities and immunosuppression therapy with outcomes were analyzed. Multiple logistic regression analysis was used to assess risk factors associated with critical COVID-19. RESULTS: Of 1198 patients with COVID-19, 169 had sarcoidosis (14.1%) and 1029 (85.9%) did not (control group). Of the 169 patients with sarcoidosis and COVID-19, 84 (49.7%) were hospitalized (study group: mean age 62.4 years; 61.9% women; and 56.0% Black). The study group required supplemental oxygen (81% vs 62%; p = 0.001) and noninvasive ventilation (33.3% vs 6.4%; p < 0.001) more often and had lower mortality (15.5% vs. 30.4%; p = 0.004) than the control group. In patients hospitalized with COVID-19, sarcoidosis was not associated with critical COVID-19 (odds ratio, 0.77; 95% CI, 0.46-1.29; p = 0.317), but having sarcoidosis while taking immunosuppression therapy was associated with decreased risk of critical COVID-19 (odds ratio, 0.45; 95% CI, 0.31-0.65; p < 0.001). CONCLUSIONS: Patients with sarcoidosis may not be at increased risk of critical illness or death from COVID-19, and immunosuppression therapy in these patients may reduce the risk of critical COVID-19.

Compression wraps as adjuvant therapy in the management of acute systolic heart failure.

Background: Guidelines recommend targeting decongestion in management of decompensated HF, with lower extremity edema often serving as the clinical target. LECW are seldom used in the acute setting, with a paucity of data on efficacy in HF, despite serving as a cornerstone of chronic lymphedema management. Primary objective: Study the efficacy and safety of LECW in acute decompensated HF. Methods: Open-label, randomized, parallel-group clinical trial. Primary outcomes: Days on intravenous (IV) diuretic therapy, total hospital length of stay (LOS), and 30-day all-cause readmission. Results: 32 patients were enrolled, with 29 patients completing the study. Enrollment was suspended due to the COVID-19 pandemic. Overall LOS was shorter in the intervention group (3.5 vs 6 days, p = 0.05), with no significant difference in total days on IV diuresis or 30-day readmission rate with use of LECW. Fewer patients required continuous diuretic infusion after treatment with LECW (0 vs 7 patients, p = 0.027). The intervention group scored significantly better on the MLWHF (55.5 vs 65, p = 0.021), including both the physical and emotional dimension scores. No adverse events were reported with use of LECW, including a significantly lower incidence of AKI (1 vs 13 patients, p = 0.005). Conclusion: The use of LECW resulted in reduced hospital LOS compared to standard therapy, with no difference in days of IV diuresis administration or 30-day readmission. Treatment with LECW also resulted in less continuous IV diuretic therapy, fewer incidence of AKI, and improved quality of life. Trends toward less escalation of diuresis, and greater reduction in edema were also observed.

Tocilizumab Associated With Survival in Patients Hospitalized for COVID-19 Acute Respiratory Distress Syndrome and Low Urine Output.

BACKGROUND: Acute respiratory distress syndrome (ARDS) with oliguria is associated with increased mortality. Interleukin-6 (IL-6) plays an integral role in the pathophysiology of both disease processes. Patients who experience severe COVID-19 have demonstrated higher IL-6 levels compared to baseline, and use of tocilizumab has demonstrated efficacy in such cohorts. We set out to investigate the relationship between tocilizumab use, COVID-19 ARDS, low urine output, and mortality. METHODS: Retrospective cohort review of adult patients aged ≥ 18 years with COVID-19 and moderate or severe ARDS, admitted to the intensive care unit (ICU) of a tertiary referral center in metropolitan Detroit. Patients were analyzed based on presence of oliguria (defined as ≤ 0.7 mL/kg/h) on the day of intubation and exposure to tocilizumab while inpatient. The primary outcome was inpatient mortality. RESULTS: One hundred and twenty-eight patients were analyzed, 103 (80%) with low urine output, of whom 30 (29%) received tocilizumab. In patients with low urine output, risk factors associated with mortality on univariate analysis included Black race (P = .028), lower static compliance (P = .015), and tocilizumab administration (P = .002). Tocilizumab (odds ratio 0.245, 95% confidence interval 0.079-0.764, P = .015) was the only risk factor independently associated with survival on multivariate logistic regression analysis. CONCLUSION: In this retrospective cohort review of patients hospitalized with COVID-19 and moderate or severe ARDS, tocilizumab administration was independently associated with survival in patients with low urine output ≤ 0.7 mL/kg/h on the day of intubation. Prospective studies are needed to investigate the impact of urine output on efficacy of interleukin-targeted therapies in the management of ARDS.

Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity.

BACKGROUND: Studies comparing SARS-CoV-2 reinfection outcomes among individuals with previous infection (natural immunity) and previous infection plus vaccination (hybrid immunity) are limited. METHODS: Retrospective cohort study comparing SARS-CoV-2 reinfection among patients with hybrid immunity (cases) and natural immunity (controls) from March 2020 to February 2022. Reinfection was defined as positive PCR> 90 days after initial laboratory-confirmed SARS-CoV-2 infection. Outcomes included time to reinfection, symptom severity, COVID-19-related hospitalization, critical COVID-19 illness (need for intensive care unit, invasive mechanical ventilation, or death), length of stay (LOS). RESULTS: A total of 773 (42%) vaccinated and 1073 (58%) unvaccinated patients with reinfection were included. Most patients (62.7%) were asymptomatic. Median time to reinfection was longer with hybrid immunity (391 [311-440] vs 294 [229-406] days, p < 0.001). Cases were less likely to be symptomatic (34.1% vs 39.6%, p = 0.001) or develop critical COVID-19 (2.3% vs 4.3%, p = 0.023). However, there was no significant difference in rates of COVID-19-related hospitalization (2.6% vs 3.8%, p = 0.142) or LOS (5 [2-9] vs 5 [3-10] days, p = 0.446). Boosted patients had longer time to reinfection (439 [IQR 372-467] vs 324 [IQR 256-414] days, p < 0.001) and were less likely to be symptomatic (26.8% vs 38%, p = 0.002) compared to unboosted patients. Rates of hospitalization, progression to critical illness and LOS were not significantly different between the two groups. CONCLUSIONS: Natural and hybrid immunity provided protection against SARS-CoV-2 reinfection and hospitalization. However, hybrid immunity conferred stronger protection against symptomatic disease and progression to critical illness and was associated with longer time to reinfection. The stronger protection conferred by hybrid immunity against severe outcomes due to COVID-19 should be emphasized with the public to further the vaccination effort, especially in high-risk individuals.

Progression to Critical Illness and Death in Patients With Breakthrough Hospitalizations.

Background: Characterization of disease progression and outcomes after coronavirus disease 2019 (COVID-19)-related hospitalization in vaccinated compared with unvaccinated individuals is limited. Methods: This was a retrospective case-control study of symptomatic vaccinated (cases) and unvaccinated (controls) participants hospitalized for COVID-19 between December 30, 2020, and September 30, 2021, in Southeast Michigan. Hospitalized adult patients with lab-confirmed COVID-19 were identified through daily census report. Breakthrough infection was defined as detection of severe acute respiratory syndrome coronavirus 2 ≥14 days after completion of the primary vaccination series. The association between prior vaccination and critical COVID-19 illness (composite of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], 28-day mortality) was examined. Results: Two hundred ten (39%) fully vaccinated and 325 (61%) unvaccinated patients were evaluated. Compared with controls, cases were older, had more comorbidities (4 [3-7] vs 2 [1-4]; P < .001), and were more likely to be immunocompromised. Cases had less severe symptoms compared with controls (2 [1-2] vs 2 [2-3]; P < .001) and were less likely to progress to critical COVID-19 illness (33.3% vs 45.5%; P < .001); 28-day mortality was significantly lower in cases (11.0% vs 24.9%; P < .001). Symptom severity (odds ratio [OR], 2.59; 95% CI, 1.61-4.16; P < .001) and modified Sequential Organ Failure Assessment score on presentation (OR, 1.74; 95% CI, 1.48-2.06; P < .001) were independently associated with development of critical COVID-19 illness. Prior vaccination (OR, 0.528; 95% CI, 0.307-0.910; P = .020) was protective. Conclusions: COVID-19-vaccinated patients were less likely to develop critical COVID-19 illness and more likely to survive. Disease severity at presentation was a predictor of adverse outcomes regardless of vaccination status.

Oliguria on the Day of Intubation Is Associated With Mortality in Patients With Acute Respiratory Distress Syndrome.

To investigate the relationship between oliguric acute kidney injury (AKI) and mortality in patients with acute respiratory distress syndrome (ARDS). DESIGN: Retrospective cohort study. SETTING: This investigation took place at a single-center, tertiary referral multidisciplinary comprehensive healthcare hospital in metropolitan Detroit, Michigan. PATIENTS: Adult patients 18 years old or older hospitalized in the ICU and diagnosed with ARDS on mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred eight patients were included in the final analysis. Risk factors associated with mortality included advanced age (p < 0.001), increased body mass index (p = 0.008), and a history of chronic kidney disease (p = 0.023). Presence of AKI by day 1 of intubation, with elevated creatinine (p = 0.003) and oliguria (p < 0.001), was significantly associated with mortality. On multivariate analysis, advanced age (relative risk [RR], 1.02), urine output on the day of intubation (RR, 0.388), bicarbonate level (RR, 0.948), and Sequential Organ Failure Assessment severity score (RR, 1.09) were independently associated with mortality. A receiver operating characteristic curve identified a threshold urine output on the day of intubation of 0.7 mL/kg/hr (area under the curve, 0.75; p < 0.001) as most closely associated with inpatient mortality (i.e., urine output < 0.7 mL/kg/hr is associated with mortality). CONCLUSIONS: For patients with ARDS, oliguria on the day of intubation was independently associated with increased mortality. Urine output of less than 0.7 mL/kg/hr predicted 80% of inpatient deaths. These findings herald an augmented understanding of the role of urine output in medical decision-making and prognostication.

Intussusception in the Setting of an Ulcerative Colitis Flare.

Intussusception is an extraordinary cause of acute abdomen in adults and has been defined as the telescoping of a bowel segment into the lumen of an adjacent segment. A 43-year-old female presented to our hospital's emergency department (ED) with 10+ episodes of bloody diarrhea per day, left-sided abdominal pain, and the inability to tolerate oral intake for one month. She was initially diagnosed with ulcerative colitis (UC) ten years ago and is currently on mesalamine oral and enema therapy. She presented to our gastroenterology clinic two weeks after the beginning of her flare and was started on prednisone 40 mg daily. This did not improve her symptoms, and she presented to the ED two weeks later. She underwent a computed tomography (CT) abdomen/pelvis which revealed intussusception in the left hemiabdomen with no definite lead point measuring 5.6 cm in the craniocaudal dimension with pneumatosis and no evidence of bowel obstruction. There were no other significant laboratory abnormalities. Acute care surgery was consulted and suggested obtaining a CT enterography for further evaluation which showed spontaneous resolution of intussusception with no evidence of pneumatosis, portal venous gas, or intraperitoneal free air. She reports that following oral contrast intake, she "felt movement and relaxation" in her abdomen with substantial pain relief. Infectious workup was negative, and therapy was initiated with intravenous steroids. In conclusion, intussusception has been very rarely reported in patients with UC with the most common treatment being surgical resection. However, conservative management in the absence of bowel obstruction can be attempted.

Nonuremic Calciphylaxis Precipitated by COVID-19 Infection.

Calciphylaxis is a rare dermatologic condition that is primarily associated with end-stage renal disease (ESRD). Nonuremic calciphylaxis has been reported in patients with autoimmune disorders such as systemic lupus erythematosus and other hypercoagulable states such as anti-phospholipid syndrome. New research throughout the COVID-19 pandemic has shown an increased inflammatory and coagulopathic complication of COVID-19. We present a case of a patient with nonuremic calciphylaxis following treatment for severe COVID-19 and no known cause of hypercoagulability. A 40-year-old Caucasian female with a history of recent COVID-19 infection requiring hospitalization, hypertension, alcohol abuse, anxiety, and one prior spontaneous miscarriage presented to the hospital with bilateral lower extremity wounds. The wounds were seen to have necrosis and eschar formation, as well as blackened mottled skin, and were extremely painful to the patient. The initial lesions were on the anterior thighs bilaterally and spread laterally and to the lower back. Initial autoimmune workup was non-specific, and biopsy confirmed calciphylaxis. Calciphylaxis is a known dermatologic disease that has high mortality and morbidity, but it is usually associated with ESRD. Some cases have been reported for autoimmune or hypercoagulable states. The disease presents with non-healing, painful skin ulcers that are at a high risk of infection and have poor healing. The case presented shows biopsy-confirmed calciphylaxis in the absence of known etiologies, and we hypothesize that it is due to COVID-19 or COVID-19 aggravating an underlying but unidentified hypercoagulable condition.

Risk Factors Associated With Hospitalization and Death in COVID-19 Breakthrough Infections.

Background: Characterizations of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections are limited. We aim to characterize breakthrough infections and identify risk factors associated with outcomes. Methods: This was a retrospective case series of consecutive fully vaccinated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a multicenter academic center in Southeast Michigan, between December 30, 2020, and September 15, 2021. Results: A total of 982 patients were identified; the mean age was 57.9 years, 565 (59%) were female, 774 (79%) were White, and 255 (26%) were health care workers (HCWs). The median number of comorbidities was 2; 225 (23%) were immunocompromised. BNT162b2 was administered to 737 (75%) individuals. The mean time to SARS-CoV-2 detection was 135 days. The majority were asymptomatic or exhibited mild to moderate disease, 154 (16%) required hospitalization, 127 (13%) had severe-critical illness, and 19 (2%) died. Age (odds ratio [OR], 1.14; 95% CI, 1.04-1.07; P < .001), cardiovascular disease (OR, 3.02; 95% CI, 1.55-5.89; P = .001), and immunocompromised status (OR, 2.57; 95% CI, 1.70-3.90; P < .001) were independent risk factors for hospitalization. Additionally, age (OR, 1.06; 95% CI, 1.02-1.11; P = .006) was significantly associated with mortality. HCWs (OR, 0.15; 95% CI, 0.05-0.50; P = .002) were less likely to be hospitalized, and prior receipt of BNT162b2 was associated with lower odds of hospitalization (OR, 0.436; 95% CI, 0.303-0.626; P < .001) and/or death (OR, 0.360; 95% CI, 0.145-0.898; P = .029). Conclusions: COVID-19 vaccines remain effective at attenuating disease severity. However, patients with breakthrough infections necessitating hospitalization may benefit from early treatment modalities and COVID-19-mitigating strategies, especially in areas with substantial or high transmission rates.

Impact of Early Corticosteroids on Preventing Clinical Deterioration in Non-critically Ill Patients Hospitalized with COVID-19: A Multi-hospital Cohort Study.

INTRODUCTION: While guidelines stronglyrecommend dexamethasone in critical COVID-19, the optimal threshold to initiate corticosteroids in non-critically ill patients with COVID-19 remains unclear. Using data from a state-wide COVID-19 registry, we evaluated the effectiveness of early corticosteroids for preventing clinical deterioration among non-critically ill patients hospitalized for COVID-19 and receiving non-invasive oxygen therapy. METHODS: This was a target trial using observational data from patients hospitalized for COVID-19 at 39 hospitals participating in the MI-COVID19 registry between March 16, 2020 and August 24, 2020. We studied the impact of corticosteroids initiated within 2 calendar days of hospitalization ("early steroids") versus no early steroids among non-ICU patients with laboratory-confirmed SARS-CoV2 receiving non-invasive supplemental oxygen therapy. Our primary outcome was a composite of in-hospital mortality, transfer to intensive care, and receipt of invasive mechanical ventilation. We used inverse probability of treatment weighting (IPTW) and propensity score-weighted regression to measure the association of early steroids and outcomes. RESULTS: Among 1002 patients meeting study criteria, 231 (23.1%) received early steroids. After IPTW, to balance potential confounders between the treatment groups, early steroids were not associated with a decrease in the composite outcome (aOR 1.1, 95%CI 0.8-1.6) or in any components of the primary outcome. CONCLUSION: We found no evidence that early corticosteroid therapy prevents clinical deterioration among hospitalized non-critically ill COVID-19 patients receiving non-invasive oxygen therapy. Further studies are needed to determine the optimal threshold for initiating corticosteroids in this population.

Mechanical Ventilation and Coronavirus Disease 2019: A Case-Control Analysis of Clinical Characteristics, Lung Mechanics, and Mortality.

OBJECTIVES: To investigate the differences in clinical course, ventilator mechanics, and outcomes of patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with a historical cohort of acute respiratory distress syndrome. DESIGN: Comparative case-control study. SETTING: Multicenter, comprehensive tertiary healthcare facility in Detroit, MI. PATIENTS/SUBJECTS: Adult patients hospitalized with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection were compared with patients hospitalized with acute respiratory distress syndrome prior to the coronavirus disease 2019 pandemic (control). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 384 patients in the analysis. Inpatient mortality was significantly higher in patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with controls (64% vs 49%; p = 0.007). Despite both groups demonstrating similar ventilatory function and Sequential Organ Failure Assessment score on day 1 of intubation, with similar lung compliance throughout the study period, patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated progressive hypoxia compared with controls across the study period. Similarly, higher positive end-expiratory pressure levels and increased use of paralytics were observed in the patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection group. On univariate analysis of the entire cohort, significant risk factors for inpatient mortality included coronavirus disease 2019 infection (p = 0.007), older age (p < 0.001), high Sequential Organ Failure Assessment score (p = 0.003), vasopressor use (p = 0.039), paralytic use (p < 0.001), higher positive end-expiratory pressure levels on day 3 (p = 0.027) and day 7 (p < 0.001), in addition to acute respiratory distress syndrome severity on both days 3 (p = 0.008) and 7 (p < 0.001). Multivariate analysis identified coronavirus disease 2019 infection (odds ratio, 1.939; p = 0.021), older age (odds ratio, 1.042; p < 0.001), paralytic use (odds ratio, 3.366; p < 0.001), and higher Sequential Organ Failure Assessment score (odds ratio, 1.152; p = 0.027) as significant predictors of mortality across the entire cohort. CONCLUSIONS: Patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated higher mortality compared with control patients hospitalized with acute respiratory distress syndrome prior to the pandemic, with progressive hypoxia throughout the study period, despite similar lung mechanics and initial Sequential Organ Failure Assessment score. Coronavirus disease 2019 infection, older age, paralytic use, and higher Sequential Organ Failure Assessment scores were independent risk factors for 28-day mortality across the entire cohort.

Visual Analytics Dashboard Promises to Improve Hypertension Guideline Implementation.

BACKGROUND: Primary care management of hypertension under new guidelines incorporates assessment of cardiovascular disease risk and commonly requires review of electronic health record (EHR) data. Visual analytics can streamline the review of complex data and may lessen the burden clinicians face using the EHR. This study sought to assess the utility of a visual analytics dashboard in addition to EHR in managing hypertension in a primary care setting. METHODS: Primary care physicians within an urban, academic internal medicine clinic were tasked with performing 2 simulated patient encounters for hypertension management: the first using standard EHR, and the second using EHR paired with a visual dashboard. The dashboard included graphical blood pressure trends with guideline-directed targets, calculated atherosclerotic cardiovascular disease risk score, and relevant medications. Guideline-appropriate antihypertensive prescribing, correct target blood pressure goal, and total encounter time were assessed. RESULTS: We evaluated 70 case simulations. Use of the dashboard with the EHR compared with use of the EHR alone was associated with greater adherence to prescribing guidelines (95% vs. 62%, P < 0.001) and more correct identification of blood pressure target (95% vs. 57%, P < 0.01). Total encounter time fell an average of 121 seconds (95% confidence interval 69-157 seconds, P < 0.001) in encounters that used the dashboard combined with the EHR. CONCLUSIONS: The integration of a hypertension-specific visual analytics dashboard with EHR demonstrates the potential to reduce time and improve hypertension guideline implementation. Further widespread testing in clinical practice is warranted.

COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases.

MOTIVATION: COVID-19 has several distinct clinical phases: a viral replication phase, an inflammatory phase and in some patients, a hyper-inflammatory phase. High mortality is associated with patients developing cytokine storm syndrome. Treatment of hyper-inflammation in these patients using existing approved therapies with proven safety profiles could address the immediate need to reduce mortality. RESULTS: We analyzed the changes in the gene expression, pathways and putative mechanisms induced by SARS-CoV2 in NHBE, and A549 cells, as well as COVID-19 lung versus their respective controls. We used these changes to identify FDA approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. We identified methylprednisolone (MP) as a potential leading therapy. The results were then confirmed in five independent validation datasets including Vero E6 cells, lung and intestinal organoids, as well as additional patient lung sample versus their respective controls. Finally, the efficacy of MP was validated in an independent clinical study. Thirty-day all-cause mortality occurred at a significantly lower rate in the MP-treated group compared to control group (29.6% versus 16.6%, P = 0.027). Clinical results confirmed the in silico prediction that MP could improve outcomes in severe cases of COVID-19. A low number needed to treat (NNT = 5) suggests MP may be more efficacious than dexamethasone or hydrocortisone. AVAILABILITY AND IMPLEMENTATION: iPathwayGuide is available at https://advaitabio.com/ipathwayguide/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Liver Injury as a Surrogate for Inflammation and Predictor of Outcomes in COVID-19.

Respiratory failure is the most common cause of death in patients with corona virus disease 2019 (COVID-19). There have been many investigations to determine predictors of bad outcomes in patients with this illness. Liver enzyme elevation has been described in hospitalized patients with severe COVID-19; however, little is known about the significance of liver injury regarding outcomes. We conducted a retrospective chart review of 348 patients admitted with COVID-19 in our quaternary care center. Liver injury on admission was defined based on the laboratory cutoff of aspartate aminotransferase >35 IU/L and/or alanine aminotransferase >52 IU/L. Patients were divided into two cohorts based on the presence or absence of liver injury. These cohorts were compared to assess differences in presentation, complications, and outcomes. The primary outcome was respiratory failure requiring intubation, and the secondary outcome was in-hospital mortality. The presence of new onset liver enzyme elevation on presentation was associated with increased severity of illness, need for mechanical ventilation, and mortality. Presence of liver injury increased the chance of acute hypoxic respiratory failure requiring mechanical ventilation by 1.79 times. The degree and timeline of liver enzyme elevation during hospitalization corresponded with elevations of other inflammatory markers. Conclusion: Liver injury appears to correlate with the inflammatory syndrome caused by COVID-19, with the degree of liver injury corresponding with severity of inflammation. We suggest early and continued monitoring of liver enzymes as they can be useful to identify patients who may need early escalation of care.

The Impact of Sociodemographic Factors, Comorbidities, and Physiologic Responses on 30-Day Mortality in Coronavirus Disease 2019 (COVID-19) Patients in Metropolitan Detroit.

BACKGROUND: The relationship of health disparities and comorbidities in coronavirus disease 2019 (COVID-19)-related outcomes are an ongoing area of interest. This report assesses risk factors associated with mortality in patients presenting with COVID-19 infection and healthcare disparities. METHODS: We conducted a retrospective cohort study of consecutive patients presenting to emergency departments within an integrated health system who tested positive for COVID-19 between 7 March and 30 April 2020 in metropolitan Detroit. The primary outcomes were hospitalization and 30-day mortality. RESULTS: A total of 3633 patients with a mean age of 58 years were included. The majority were female and Black non-Hispanic. Hospitalization was required for 64% of patients, 56% of whom were Black. Hospitalized patients were older, more likely to reside in a low-income area, and had a higher burden of comorbidities. By 30 days, 433 (18.7%) hospitalized patients died. In adjusted analyses, the presence of comorbidities, an age >60 years, and more severe physiological disturbance were associated with 30-day mortality. Residence in low-income areas (odds ratio [OR], 1.02; 95% confidence interval [CI], .76-1.36) and public insurance (OR, 1.24; 95% CI, .76-2.01) were not independently associated with a higher risk of mortality. Black female patients had a lower adjusted risk of mortality (OR, 0.46; 95% CI, .27-.78). CONCLUSIONS: In this large cohort of COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Disparities in income or source of health insurance were not associated with outcomes. Black women had a lower risk of dying.