Faculty Bibliography

RATIONALE/BACKGROUND:No direct comparisons of clinical features, laboratory values, and outcomes between critically ill patients with COVID-19 and influenza in the United States have been reported. OBJECTIVE:To evaluate the risk of mortality comparing critically ill patients with COVID-19 to seasonal influenza. METHODS:We retrospectively identified patients admitted to the intensive care units (ICUs) at two academic medical centers with laboratory confirmed SARS-CoV-2 or influenza A or B infections between January 1, 2019 and April 15, 2020. Clinical data were obtained by medical record review. All patients except one had follow-up to hospital discharge or death. We used relative risk regression adjusting for age, sex, number of comorbidities, and maximum sequential organ failure scores (SOFA) on ICU day 1 to determine the risk of hospital mortality and organ dysfunction in patients with COVID-19 compared to influenza. RESULTS:We identified 65 critically ill patients with COVID-19 and 74 with influenza. The mean (± standard deviation) age in each group was 60.4 +/- 15.7 and 56.8 +/- 17.6 years, respectively. Patients with COVID-19 were more likely to be male, have higher body mass index and higher rates of chronic kidney disease and diabetes. Thirty-seven percent of COVID-19 patients identified as Hispanic, compared to 10% of influenza patients. A similar proportion of patients had fever (~40%) and lymphopenia (~80%) on hospital presentation. Rates of acute kidney injury and shock requiring vasopressors were similar between the groups. While need for invasive mechanical ventilation was also similar in both groups, patients with COVID-19 had slower improvements in oxygenation, longer durations of mechanical ventilation, and lower rates of extubation compared to patients with influenza. Hospital mortality was 40% in COVID-19 patients and 19% in influenza patients (adjusted relative risk 2.13, 95% confidence interval 1.24 to 3.63; p = 0.006). CONCLUSIONS:Need for invasive mechanical ventilation was common in ICU patients with COVID-19 or influenza. Compared to those with influenza, ICU patients with COVID-19 had worse respiratory outcomes, including longer duration of mechanical ventilation. Additionally, patients with COVID-19 were at greater risk for in-hospital mortality, independent of age, sex, co-morbidities, and ICU severity of illness.

AIMS/OBJECTIVE:Sacubitril/valsartan combines renin-angiotensin-aldosterone system inhibition with amplification of natriuretic peptides. In addition to well-described effects, natriuretic peptides exert direct effects on pulmonary vasculature. The effect of sacubitril/valsartan on pulmonary artery pressure (PAP) has not been fully defined. METHODS AND RESULTS/RESULTS:This was a retrospective case-series of PAP changes following transition from angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) to sacubitril/valsartan in patients with heart failure reduced ejection fraction and a previously implanted CardioMEMS™ sensor. Pre-sacubitril/valsartan and post-sacubitril/valsartan PAPs were compared for each patient by examining averaged consecutive daily pressure readings from 1 to 5 days before and after sacubitril/valsartan exposure. PAP changes were also compared between patients based on elevated trans-pulmonary gradients (trans-pulmonary gradient ≥ 12 mmHg) at time of CardioMEMS™ sensor implantation. The cohort included 18 patients, 72% male, mean age 60.1 ± 13.6 years. There was a significant decrease in PAPs associated with transition from ACEI/ARB to sacubitril/valsartan. The median (interquartile range) pre-treatment and post-treatment change in mean, systolic and diastolic PAPs were -3.6 (-9.8, -0.7) mmHg (P < 0.001), -6.5 (-15.0, -2.0) mmHg (P = 0.001), and -2.5 (-5.7, -0.7) (P = 0.001), respectively. The decrease in PAPs was independent of trans-pulmonary gradient (F(1,16) = 0.49, P = 0.49). CONCLUSIONS:In this retrospective case series, transition from ACEI/ARB to sacubitril/valsartan was associated with an early and significant decrease in PAPs.

Kratom is an unregulated kappa-opioid receptor agonist available for order on the internet that is used as a remedy for chronic pain. We present a case of a middle-aged man who suffered a cardiac arrest in the setting of kratom ingestion.

OBJECTIVE/UNASSIGNED:This study aimed to examine differences in completion rates between telepsychiatry and in-person visits during the COVID-19 pandemic and a prior reference period. METHODS/UNASSIGNED:The authors used electronic medical record data along with chi-squared or t tests to compare patients' demographic characteristics. Generalized estimating equations for estimating the odds of primary and secondary outcomes were used, controlling for demographic characteristics. RESULTS/UNASSIGNED:During COVID-19, the odds of completing a telepsychiatry visit (N=26,715) were 6.68 times the odds of completing an in-person visit (N=11,094). The odds of completing a telepsychiatry visit during COVID-19 were 3.00 times the odds of completing an in-person visit during the pre-COVID-19 reference period (N=40,318). CONCLUSIONS/UNASSIGNED:In this cross-sectional study, outpatient adult mental health clinic telepsychiatry appointments, largely by telephone, were strongly associated with a higher rate of visit completion compared with in-person visits during and prior to the COVID-19 pandemic. Regulators should consider permanently enabling reimbursement for telephone-only telepsychiatry visits.

Atherosclerosis is a disease of chronic inflammation. We investigated the roles of the cytokines IL-4 and IL-13, the classical activators of STAT6, in the resolution of atherosclerosis inflammation. Using Il4^-/-Il13^-/- mice, resolution was impaired, and in control mice, in both progressing and resolving plaques, levels of IL-4 were stably low, and IL-13 was undetectable. This suggested that IL-4 is required for atherosclerosis resolution, but collaborates with other factors. We had observed increased Wnt signaling in macrophages in resolving plaques, and human genetic data from others showed that a loss-of-function Wnt mutation was associated with premature atherosclerosis. We now find an inverse association between activation of Wnt signaling and disease severity in mice and humans. Wnt enhanced the expression of inflammation resolving factors after treatment with plaque-relevant low concentrations of IL-4. Mechanistically, activation of the Wnt pathway following lipid lowering potentiates IL-4 responsiveness in macrophages via a PGE₂/STAT3 axis.

Issue: Calls to change medical education have been frequent, persistent, and generally limited to alterations in content or structural re-organization. Self-imposed barriers have prevented adoption of more radical pedagogical approaches, so recent predictions of the 'inevitability' of medical education transitioning to online delivery seemed unlikely. Then in March 2020 the COVID-19 pandemic forced medical schools to overcome established barriers overnight and make the most rapid curricular shift in medical education's history. We share the collated reports of nine medical schools and postulate how recent responses may influence future medical education. Evidence: While extraneous pandemic-related factors make it impossible to scientifically distinguish the impact of the curricular changes, some themes emerged. The rapid transition to online delivery was made possible by all schools having learning management systems and key electronic resources already blended into their curricula; we were closer to online delivery than anticipated. Student engagement with online delivery varied with different pedagogies used and the importance of social learning and interaction along with autonomy in learning were apparent. These are factors known to enhance online learning, and the student-centered modalities (e.g. problem-based learning) that included them appeared to be more engaging. Assumptions that the new online environment would be easily adopted and embraced by 'technophilic' students did not always hold true. Achieving true distance medical education will take longer than this 'overnight' response, but adhering to best practices for online education may open a new realm of possibilities. Implications: While this experience did not confirm that online medical education is really 'inevitable,' it revealed that it is possible. Thoughtfully blending more online components into a medical curriculum will allow us to take advantage of this environment's strengths such as efficiency and the ability to support asynchronous and autonomous learning that engage and foster intrinsic learning in our students. While maintaining aspects of social interaction, online learning could enhance pre-clinical medical education by allowing integration and collaboration among classes of medical students, other health professionals, and even between medical schools. What remains to be seen is whether COVID-19 provided the experience, vision and courage for medical education to change, or whether the old barriers will rise again when the pandemic is over.