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

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

When is indicated viscosupplementation in hip osteoarthritis?

Background and aim The incidence of hip osteoarthritis (OA) is increasing in parallel with the aging of the population. The aim of this study is to report the efficacy of an ultrasound-guided intra-articular (IA) hip injection of a single dose of high-weight hyaluronic acid (HA) (2500 kDa) at a follow-up of 12 months. Materials and Methods 226 patients older than 40 years of age affected by painful hip OA (Kellgren-Lawrence stage 1-2-3) were treated from January 2012 to December 2015 with viscosupplementation. Patients were clinically evaluated before injection (T0) and after 3 months (T3), 6 months (T6) and 1 year (T3) through the WOMAC scale and Harris Hip Score (HHS). Results During the follow-up period no patients underwent to hip surgery or need adjunctive IA injection of HA. No adverse effects were registered. An improvement in WOMAC and HHS was observed in all patients after treatment. Results showed that patients with grade 2 of osteoarthritis had the higher delta of change in the scores.  Discussion Ultrasound-guided with high weight IA HA injection could be a possibility of treatment in the symptomatic osteoarthritic hip. Subjects with a moderate grade of osteoarthritis (Kellgren-Lawrence stage 2) represent the group that could report the maximum benefits from viscosupplementation

Pubalgia and soccer: real problem or overestimated?/La pubalgia del calciatore: problema reale o sopravvalutato?

SUMMARY Aim. “Pubalgia like” syndromes in the athletes should not be underestimated because they are often associated with a high morbidity, which leads to time away from training and competition. The aim of the study was to verify the accuracy of an initial generic diagnosis of athletic pubalgia in professional soccer players. Methods. In this study 44 athletes were selected and divided into 2 groups: group A was composed of 22 patients with anterior groin pain and generic diagnosis of athletic pubalgia and group B of 22 healthy patients. Each player underwent a clinical and instrumental evaluation with pelvis’ x-rays (antero-posterior and oblique “frog” views) and weigthbearing full-length hip-to-ankle radiographs of the lower limb. Furthermore, symptomatic patients performed a pelvis’ magnetic resonance imaging. Results. A percentage of 50% of the players were affected by a true athletic pubalgia, while the others by different pathologies. In particular, 18.2% of patients had a femoroacetabular impingement, 18.2% a leg length discrepancy, 4.5% an avulsion of the anterior inferior iliac spine, 4.5% a varicocele and the 4.5% a proximal incomplete rectus femoris tendon rupture. Moreover, results showed that midfielders players were more frequently affected by this type of pathology (81%). Conclusion. Results suggested that athletic pubalgia may be the real cause of anterior groin pain in a considerable number of cases, but is always necessary to consider other pathologies or morpho-structural anomalies which could be associated or be the cause of this symptomatology. RIASSUNTO Scopo. Le sindromi pubalgiche del calciatore non devono essere sottovalutate poiché spesso risultano essere associate a elevata morbidità con assenze prolungate dall’attività sportiva. L’obiettivo dello studio è stato quello di verificare la correttezza della diagnosi iniziale di pubalgia in calciatori professionisti o se il dolore derivasse da altre patologie o alterazioni morfo-strutturali. Metodi. In questo studio sono stati valutati 44 atleti, suddivisi in 2 gruppi: il primo di 22 pazienti con dolore pelvico anteriore e diagnosi generica di pubalgia e il secondo di 22 pazienti asintomatici. Per ogni giocatore è stata eseguita una valutazione clinica e strumentale con radiografie del bacino e teleradiografie degli arti inferiori e, inoltre, in quelli sintomatici una risonanza magnetica del bacino. Risultati. Il 50% dei pazienti era affetto da una reale pubalgia e il 50% da altre problematiche. In particolare il 18,2% dei casi presentava un impingement femoro-acetabolare, il 18,2% una dismetria degli arti inferiori, il 4,5% un’avulsione della spina iliaca antero-inferiore, il 4,5% un varicocele e il 4,5% una rottura tendinea incompleta del retto femorale all’inserzione prossimale. La statistica descrittiva ha inoltre dimostrato come l’81,1% dei casi con pubalgia interessasse i centrocampisti.Conclusioni. Dai risultati ottenuti si evince come la pubalgia possa essere la reale causa di dolore pelvico anteriore in un numero considerevole di casi, ma è comunque necessario considerare nella diagnosi differenziale altre patologie o alterazioni morfo-strutturali che possono essere la causa di tale sintomatologia

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic : an international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Observation of WWWWWW Production in pppp Collisions at s\sqrt s =13 TeV with the ATLAS Detector

International audienceThis Letter reports the observation of $WWW$ production and a measurement of its cross section using 139 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. Events with two same-sign leptons (electrons or muons) and at least two jets, as well as events with three charged leptons, are selected. A multivariate technique is then used to discriminate between signal and background events. Events from $WWW$ production are observed with a significance of 8.0 standard deviations, where the expectation is 5.4 standard deviations. The inclusive $WWW$ production cross section is measured to be $820 \pm 100\,\text{(stat)} \pm 80\,\text{(syst)}$ fb, approximately 2.6 standard deviations from the predicted cross section of $511 \pm 18$ fb calculated at next-to-leading-order QCD and leading-order electroweak accuracy