Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Failure to Rescue: A New Society of Thoracic Surgeons Quality Metric for Cardiac Surgery.

BACKGROUND: Failure to rescue (FTR) focuses on the ability to prevent death among patients who experience postoperative complications. The Society of Thoracic Surgeons (STS) Quality Measurement Task Force has developed a new, risk- adjusted FTR quality metric for adult cardiac surgery. METHODS: The study population was taken from 1118 STS Adult Cardiac Surgery Database participants including patients who underwent isolated CABG, aortic valve replacement +/- CABG, or mitral valve repair/replacement, +/- CABG between January, 2015 and June, 2019. The FTR analysis was derived from patients who experienced ≥ 1 of the following complications: prolonged ventilation, stroke, reoperation, and renal failure. Data were randomly split into 70% training (n=89,059) and 30% validation samples (n=38,242),Risk variables included STS predicted risk of mortality, operative procedures, and intraoperative variables (cardiopulmonary bypass and cross-clamp times, unplanned procedures, need for circulatory support, and massive transfusion). RESULTS: Overall mortality for the for patients undergoing any of the index operations during the study period was 2.6% (27,045/1,058,138), with mortality of 0.9% (8,316/930,837), 8.0% (7,618/94,918), 30.6% (8,247/26,934), 51.9%(2,661/5,123), and 62.3% (203/326) among patients suffering none, one, two, three or four complications. FTR risk model calibration was excellent, as were model discrimination (c-statistic 0.806) and the Brier score (0.102). Using 95% Bayesian credible intervals, 62 (5.6%) participants performed worse and 53 (4.7%) participants performed better than expected. CONCLUSIONS: A new risk-adjusted FTR metric has been developed which complements existing STS performance measures. The metric specifically assesses institutional effectiveness of postoperative care, allowing hospitals to target quality improvement efforts

The Society of Thoracic Surgeons 2018 Adult Cardiac Surgery Risk Models: Part 1-Background, Design Considerations, and Model Development.

BACKGROUND: The last published version of The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) risk models were developed in 2008 based on patient data from 2002 to 2006 and have been periodically recalibrated. In response to evolving changes in patient characteristics, risk profiles, surgical practice, and outcomes, the STS has now developed a set of entirely new risk models for adult cardiac surgery. METHODS: New models were estimated for isolated coronary artery bypass grafting surgery (CABG [n = 439,092]), isolated aortic or mitral valve surgery (n = 150,150), and combined valve plus CABG procedures (n = 81,588). The development set was based on July 2011 to June 2014 STS ACSD data; validation was performed using July 2014 to December 2016 data. Separate models were developed for operative mortality, stroke, renal failure, prolonged ventilation, reoperation, composite major morbidity or mortality, and prolonged or short postoperative length of stay. Because of its low occurrence rate, a combined model incorporating all operative types was developed for deep sternal wound infection/mediastinitis. RESULTS: Calibration was excellent except for the deep sternal wound infection/mediastinitis model, which slightly underestimated risk because of higher rates of this endpoint in the more recent validation data; this will be recalibrated in each feedback report. Discrimination (c-index) of all models was superior to that of 2008 models except for the stroke model for valve patients. CONCLUSIONS: Completely new STS ACSD risk models have been developed based on contemporary patient data; their performance is superior to that of previous STS ACSD models