Aldehyde dehydrogenases (ALDH) catalyze the conversion of various aliphatic and aromatic aldehydes to corresponding carboxylic acids.  Traditionally considered as housekeeping enzymes, new biochemical roles are being identified for members of ALDH family.  Recent work showed that AldA from the plant pathogen Pseudomonas syringae strain PtoDC3000 functions as an indole-3-acetaldehyde dehydrogenase for the synthesis of indole-3-acetic acid (IAA).  IAA produced by AldA allows the pathogen to suppress salicylic acid-mediated defenses in the model plant Arabidopsis thaliana.  Here we present a biochemical and structural analysis of the AldA indole-3-acetaldehyde dehydrogenase from PtoDC3000.  Site-directed mutants targeting the catalytic residues Cys302 and Glu267 resulted in a loss of enzymatic activity.  The x-ray crystal structure of the catalytically inactive AldA C302A mutant in complex with IAA and NAD+ showed the cofactor adopting a conformation that differs from the previously reported structure of AldA.  These structures suggest that NAD+ undergoes a conformational change during the AldA reaction mechanism similar to that reported for human ALDH.  Site-directed mutagenesis of the IAA binding site indicates that changes in the active site surface reduces AldA activity; however, substitution of Phe169 with a tryptophan altered the substrate selectivity of the mutant to prefer octanal.  This study highlights the inherent biochemical versatility of members of the ALDH enzyme superfamily in P. syringae.

IntroductionDiabetes mellitus is a common comorbidity among patients with coronavirus disease 2019 (COVID-19). Diabetic patients with COVID-19 have a two-fold increased risk of death and tend to have more severe infection compared to the general population. Metformin, a first-line medication for diabetes management, has anti-inflammatory and immunomodulatory effects. Previous studies focusing on metformin and COVID-19 clinical outcomes have had mixed results, with some showing a mortality benefit or decreased complications with metformin use. To date, few studies have analyzed such outcomes among a diverse, multiracial community.MethodsThis was a retrospective review of patients with Type 2 diabetes and a confirmed COVID-19 infection admitted to an urban academic medical center from January 1, 2020 to May 7, 2020. Baseline characteristics were collected. The primary outcomes of the study were in-hospital mortality and length of stay (LOS).ResultsA total of 4462 patients with Type 2 diabetes and confirmed COVID-19 were identified. 41.3% were Black, and 41.5% were Hispanic. There were 1021 patients in the metformin group and 3441 in the non-metformin group. Of note, more participants in the metformin group had comorbid disease and/or advanced diabetes. We found no statistically significant differences between the metformin and non-metformin group in in-hospital mortality (28.1% vs 25.3%, P=0.08) or length of hospital stay in days (7.3 vs. 7.5, P=0.59), even after matching patients on various factors (29.3% vs. 29.6%, P=0.87; 7.7 vs. 8.1, P=0.23).ConclusionWhile patients had more comorbid disease and advanced diabetes in the metformin group, there were no significant differences with regard to in-hospital mortality or length of stay due to COVID-19 compared to the non-metformin group. Prospective studies are needed to determine if there is clinical benefit for initiating, continuing, or re-initiating metformin in patients hospitalized with COVID-19.

Introduction: The COVID-19 pandemic surge necessitated a rapid increase in provision of goals of care communication for patients with respiratory failure and high risk of death. We aimed to describe the outcomes and incidence of code status changes for mechanically ventilated patients in an acute care hospital after deploying strategies to enhance primary palliative care, including provision of goals of care communication scripts to front-line physicians. Methods: This is a retrospective cohort study including all patients admitted with COVID-19 disease and requiring mechanical ventilation during a 2-week period in March and April of 2020. Results: Of the 440 total patients, 327 (74.3%) died. 162 patients received a documented attempt at cardiopulmonary resuscitation (CPR) and only 4 (2.5%) of them survived. No patient above the age of 64 survived a CPR attempt. On admission, 404 patients (92.8%) were Full Code. 165 patients (37.5%) had a code status change. Almost half of the patients (n = 219) had a palliative care consult. Patients with a palliative care consult were more likely to have a code status change (56.6% v. 18.6%, χ2 = 68.0, p < 0.01). Discussion: Mechanically ventilated patients had a high mortality, and CPR did not result in survival to discharge in patients over 65. Palliative care specialists are needed to guide goals of care discussions during the COVID-19 pandemic, as there are numerous barriers to equipping primary care teams to lead such discussions. The COVID-19 pandemic has underscored the vital role of palliative care in disaster response.