Peri-operative score for elderly patients with resectable hepatocellular carcinoma

BACKGROUND Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma(HCC),also in elderly population.Despite this,the evaluation of patient condition,liver function and extent of disease remains a demanding process with the aim to reduce postoperative morbidity and mortality.AIM To identify new perioperative risk factors that could be associated with higher 90-and 180-d mortality in elderly patients eligible for liver resection for HCC considering traditional perioperative risk scores and to develop a risk score.METHODS A multicentric,retrospective study was performed by reviewing the medical records of patients aged 70 years or older who electively underwent liver resection for HCC;several independent variables correlated with death from all causes at 90 and 180 d were studied.The coefficients of Cox regression proportional-hazards model for sixmonth mortality were rounded to the nearest integer to assign risk factors'weights and derive the scoring algorithm.RESULTS Multivariate analysis found variables(American Society of Anesthesiology score,high rate of comorbidities,Mayo end stage liver disease score and size of biggest lesion)that had independent correlations with increased 90-and 180-d mortality.A clinical risk score was developed with survival profiles.CONCLUSION This score can aid in stratifying this population in order to assess who can benefit from surgical treatment in terms of postoperative mortality.

Impact of body mass index in elderly patients treated with laparoscopic liver resection for hepatocellular carcinoma

BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated.AIM To evaluate the impact of high body mass index(BMI)on perioperative and oncological outcome in elderly patients(>70 years old)treated with laparoscopic liver resection for hepatocellular carcinoma(HCC).METHODS Retrospective multicenter study including 224 elderly patients(>70 years old)operated by laparoscopy for HCC(196 with a BMI<30 and 28 with BMI≥30),observed from January 2009 to January 2019.RESULTS After propensity score matching,patients in two groups presented comparable results,in terms of operative time(median range:200 min vs 205 min,P=0.7 respectively in non-obese and obese patients),complications rate(22%vs 26%,P=1.0),length of hospital stay(median range:4.5 d vs 6.0 d,P=0.1).There are no significant differences in terms of short-and long-term postoperative results.CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC.

Long-Term Persistent Absolute Insulin Secretion Deficiency in Diabetes Induced by Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are today an immense hope in the management of cancers. However, since their widespread use, many cases of insulin-requiring diabetes appearing suddenly, as fulminant diabetes have been reported. Here, we describe 4 cases that occurred at different times after the beginning of immune checkpoint inhibitor therapy with Nivolumab alone or associated with Ipilimumab. There are 3 cases of newly diagnosed diabetes and 1 case of known type 2 diabetes formerly quite well balanced with Metformin. The clinical and biological characteristics of these patients are quite similar. They were all insulin-requiring at the discovery of diabetes and remained so throughout their follow-up. This type of diabetes which looks like type 1 diabetes seems rather to be a new entity.

Evaluating pediatric ureteropelvic junction obstruction:Dynamic magnetic resonance urography vs renal scintigraphy 99mtechnetium mercaptoacetyltriglycine

BACKGROUND Ureteropelvic junction obstruction(UPJO)is a common congenital urinary tract disorder in children.It can be diagnosed as early as in utero due to the presence of hydronephrosis or later in life due to symptomatic occurrence.AIM To evaluate the discrepancy between dynamic contrast-enhanced magnetic resonance urography(dMRU)and scintigraphy 99m-technetium mercaptoacetyltriglycine(MAG-3)for the functional evaluation of UPJO.METHODS Between 2016 and 2020,126 patients with UPJO underwent surgery at Robert DebréHospital.Of these,83 received a prenatal diagnosis,and 43 were diagnosed during childhood.Four of the 126 patients underwent surgery based on the clinical situation and postnatal ultrasound findings without undergoing functional imaging evaluation.Split renal function was evaluated preoperatively using scintigraphy MAG-3(n=28),dMRU(n=53),or both(n=40).In this study,we included patients who underwent surgery for UPJO and scintigraphy MAG-3+dMRU but excluded those who underwent only scintigraphy MAG-3 or dMRU.The patients were divided into groups A(<10%discrepancy)and B(>10%discrepancy).We examined the discrepancy in split renal function between the two modalities and investigated the possible risk factors.RESULTS The split renal function between the two kidneys was compared in 40 patients(28 boys and 12 girls)using scintigraphy MAG-3 and dMRU.Differential renal function,as determined using both modalities,showed a difference of<10%in 31 children and>10%in 9 children.Calculation of the relative renal function using dMRU revealed an excellent correlation coefficient with renal scintigraphy MAG-3 for both kidneys.CONCLUSION Our findings demonstrated that dMRU is equivalent to scintigraphy MAG-3 for evaluating split renal function in patients with UPJO.

Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?

Pancreatic ductal adenocarcinoma(PDAC)is one of the deadliest cancers,mostly due to its resistance to treatment.Of these,checkpoint inhibitors(CPI)are inefficient when used as monotherapy,except in the case of a rare subset of tumors harboring microsatellite instability(<2%).This inefficacy mainly resides in the low immunogenicity and non-inflamed phenotype of PDAC.The abundant stroma generates a hypoxic microenvironment and drives the recruitment of immunosuppressive cells through cancerassociated-fibroblast activation and transforming growth factorβsecretion.Several strategies have recently been developed to overcome this immunosuppressive microenvironment.Combination therapies involving CPI aim at increasing tumor immunogenicity and promoting the recruitment and activation of effector T cells.Ongoing studies are therefore exploring the association of CPI with vaccines,oncolytic viruses,MEK inhibitors,cytokine inhibitors,and hypoxia-and stroma-targeting agents.Adoptive T-cell transfer is also under investigation.Moreover,translational studies on tumor tissue and blood,prior to and during treatment may lead to the identification of biomarkers with predictive value for both clinical outcome and response to immunotherapy.

Helpfulness of the combination of acetic acid and FICE in the detection of Barrett's epithelium and Barrett's associated neoplasias

AIM:To investigate the mucosal morphology in Barrett's oesophagus by chromo and magnifying endoscopy.METHODS:A prospective pilot study at a tertiary medical centre was conducted to evaluate the use of acetic acid pulverisation combined with virtual chromoendoscopy using Fujinon intelligent chromoendoscopy(FICE) for semiological characterization of the mucosal morphology in Barrett's oesophagus and its neoplastic complications.Upper endoscopy using high definition whitelight,2% acid acetic pulverisation and FICE with high definition videoendoscopy were performed in 20 patients including 18 patients who presented with aspects of Barrett's oesophagus at endoscopy examination.Two patients used as controls had normal endoscopy and histological results.Prospectively,videos were watched blind from histological results by three trained FICE technique endoscopists.RESULTS:The videos of patients with high-grade dysplasia showed an irregular mucosal pattern in 14% using high definition white light endoscopy and in 100% using acid acetic-FICE combined.Videos did not identify irregular vascular patterns using high definition white light endoscopy,while acid acetic-FICE combined visualised one in 86% of cases.CONCLUSION:Combined acetic acid and FICE is a promising method for screening high-grade dysplasia and early cancer in Barrett's oesophagus.

Hepatitis B and human immunodeficiency virus co-infection

Hepatitis B and human immunodeficiency virus(HBV and HIV)infection share transmission patterns and risk factors,which explains high prevalence of chronic HBV infection in HIV infected patients.The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection,faster progression to cirrhosis and higher risk of liver-related death in HIVHBV co-infected patients than in HBV mono-infected ones.HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma.Noninvasive tools are now available to evaluate liver fibrosis.Isolated hepatitis B core antibodies(anti-HBc)are a good predictive marker of occult HBV infection.Still the prevalence and significance of occult HBV infection is controversial,but its screening may be important in the management of antiretroviral therapy.Vaccination against HBV infection is recommended in non-immune HIV patients.The optimal treatment for almost all HIV-HBV co-infectedpatients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation.Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen.The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.

Portal hypertensive duodenal polyp:A case report

Abnormalities of gastric mucosa in patients with portal hypertension are well documented. Manifestations of portal hypertension in small bowel and colon are less common. Colonic polypoid lesions microscopically consisting of a normal mucosa, with dilatation of submucosal vessels, have been described. We here report the first case of portal hypertensive duodenal polyp, responsible for gastro-intestinal bleeding. Endoscopic treatment turned out to be successful.

Quality of life, physical performance and nutritional status in older patients hospitalized in a cardiology department

Objectives Quality of life(QoL) is a priority outcome in older adults suffering from cardiovascular diseases. Frailty and poor nutritional status may affect the QoL through mobility disorders and exhaustion. The objective of this study was to determine if physical frailty and nutritional status were associated with QoL, in older cardiology patients. Methods Cross sectional, observational study conducted in a cardiology department from a university hospital. Participants(n = 100) were aged 70 and older. Collected data included age, sex, cardiac diseases, New York Heart Association(NYHA) classification, comorbidities(Charlson Index) and disability. A Short Physical Performance Battery(SPPB), including walking speed assessment was performed;handgrip strength were measured as well as Fried’s frailty phenotype. Nutritional status was assessed using the Mini Nutritional Assessment(MNA) and Body Mass Index(BMI), inflammation by C-reactive protein(CRP). QoL was assessed using the EORTC–QLQ questionnaire. Univariate and multivariate analyses were performed to study the associations between all recorded parameters and QoL. Results In participants(mean age: 79.3 ± 6.7 years;male: 59%), Charlson index, arrhythmia, heart failure, NYHA class III-IV, MNA, disability, walking speed, SPPB score, frailty and CRP were significantly associated with QoL in univariate analysis. Multivariate analysis showed that NYHA class III-IV(P < 0.001), lower MNA score(P = 0.03), frailty(P < 0.0001), and higher CRP(P < 0.001) were independently associated with decreased QoL. Conclusions Frailty, nutritional status and inflammation were independently associated with poor QoL. Further studies are needed to assess the efficacy of nutritional and physical interventions on QoL in this population.

Liver resection and metabolic disorders: An undescribed mechanism leading to postoperative mortality

AIM: To investigate the mechanism leading to perioperative mortality in patients undergoing major liver resection and presenting with metabolic disorders.METHODS: The link between Metabolic Syndrome and non-alcoholic fatty liver disease is currently demonstrated. Various metabolic disorders and the Metabolic Syndrome(the association of ≥ 3 metabolic disorders) have been recently described as a risk factor of perioperative mortality in major liver resection. Patients who passed away during perioperative course of major liver resection and presenting with the association of ≥ 2 metabolic disorders without any other known cause of liver disorders were reviewed.RESULTS: From January 2001 to May 2010 in a tertiary centre, ten patients presenting with ≥ 2 metabolic disorders without any other known cause of liver disorders died during perioperative course of major liver resection. The same four-consecutive-steps sequence of events occurred, including jaundice. The analysis of this series suggested a rapidly deteriorating congestive liver resulting in an increased portal hypertension leading to hepatorenal syndrome and lately to multiorgan failure(mimicking septic collapse) as the mechanism leading to exitus. The acute portal hypertension is mainly related to the surgical procedure. The chronic portal hypertension is indeterminate. Patients with ≥ 2 metabolic disorders should be considered as potentially presenting with portal hypertension possibly evolving towards hepatorenal syndrome; thus, they should be considered as having a high perioperative risk and should be carefully evaluated before undergoing major liver resection.CONCLUSION: As fibrosis was not present or marginal in liver specimens, the real cause of portal hypertension in patients with multiple metabolic disorders should be investigated with further studies.

Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma(PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment(TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy-most commonly using a local high single dose-are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.

Impact of venous thromboembolism on the natural history of pancreatic adenocarcinoma

Few studies have analyzed the effect of ve- nous thromboembolism （VTE） events on the prognosis of pancreatic cancer, but their results were conflicting. The pres- ent study was undertaken to determine the effect of VTE on pancreatic adenocarcinoma （PA） outcomes. METHODS： All consecutive patients diagnosed with PA from May 2004 to January 2012 in a single oncology center were retrospectively studied. Clinical, radiological and histologi- cal data at time of diagnosis or within the first 3 months after surgery, including the presence （＋） or absence （-） of VTE were collected. VTE was defined as radiological evidence of either pulmonary embolism （PE）, deep venous thrombosis without infection or catheter-related thrombosis. PA with and without PE was compared for survival using the Kaplan-Meier method to estimate overall survival. RESULTS： Among 162 PA patients with a median follow-up of 15 （3-92） months after diagnosis, 28 demonstratedVTE （＋）. PA patients with and without PE were similar for age, American Society of Anesthesiologist score, body mass index, and histo- ry of treatment. The distribution of cancer stages was similarbetween the two groups VTE （＋） and VTE （-）. The median du- ration of survival was significantly worse in the VTE （＋） group vs VTE （-） （12 vs 18 months, P=0.010）. In multivariate analysis, the presence of VTE and surgical treatment were independent prognostic factors for overall survival. CONCLUSION： VTE （＋） at time of diagnosis or within the first 3 months after surgery during treatment is an indepen- dent factor of poor prognosis in PA.

Characterization of two rat models of cystic fibrosis—KO and F508del CFTR—Generated by Crispr-Cas9

Background: Genetically engineered animals are essential for gaining a proper understanding of the disease mechanisms of cystic fibrosis(CF). The rat is a relevant laboratory model for CF because of its zootechnical capacity, size, and airway characteristics, including the presence of submucosal glands.Methods: We describe the generation of a CF rat model(F508 del) homozygous for the p.Phe508 del mutation in the transmembrane conductance regulator(Cftr) gene. This model was compared to new Cftr-/-rats(CFTR KO). Target organs in CF were examined by histological staining of tissue sections and tooth enamel was quantified by micro-computed tomography. The activity of CFTR was evaluated by nasal potential difference(NPD) and short-circuit current measurements. The effect of VX-809 and VX-770 was analyzed on nasal epithelial primary cell cultures from F508 del rats.Results: Both newborn F508 del and Knock out(KO) animals developed intestinal obstruction that could be partly compensated by special diet combined with an osmotic laxative. The two rat models exhibited CF phenotypic anomalies such as vas deferens agenesis and tooth enamel defects. Histology of the intestine, pancreas, liver, and lungs was normal. Absence of CFTR function in KO rats was confirmed ex vivo by short-circuit current measurements on colon mucosae and in vivo by NPD, whereas residual CFTR activity was observed in F508 del rats. Exposure of F508 del CFTR nasal primary cultures to a combination of VX-809 and VX-770 improved CFTR-mediated Cl-transport.Conclusions: The F508 del rats reproduce the phenotypes observed in CFTR KO animals and represent a novel resource to advance the development of CF therapeutics.

Diagnostic errors of nasal fractures in the emergency department:A monocentric retrospective study

Nasal bone fracture is one of the most common face bone injuries and the third most frequent of all body fractures.[1]Clinical examination is considered to be the gold standard to confirm the diagnosis of a nasal fracture.However,diagnosis may be challenging in case of haematoma and oedema of adjacent tissues,this leading to the use of X-rays to confirm or infirm the hypothesis.[2]Radiographic explorations for midface traumas can also be indicated for forensic purposes.[3]

Cyclin-dependent kinase inhibitors p21 and p27 function as critical regulators of liver regeneration following 90%hepatectomy in the rat

BACKGROUND Liver reduction is the main curative treatment for primary liver cancer,but its use remains limited as liver regeneration requires a minimum of 30%functional parenchyma.AIM To study the dynamics of the liver regeneration process and consequent behavior of cell cycle regulators in rats after extended hepatectomy(90%)and postoperative glucose infusions.METHODS Post-hepatectomy liver failure was triggered in 84 Wistar rats by reducing their liver mass by 90%.The animals received a post-operative glucose infusion and were randomly assigned to two groups:One to investigate the survival rate and the other for biochemical analyses.Animals that underwent laparotomy or 70%hepatectomy were used as controls.Blood and liver samples were collected on postoperative days 1 to 7.Liver morphology,function,and regeneration were studied with histology,immunohistochemistry,and western blotting.RESULTS Postoperative mortality after major resection reached 20%and 55%in the first 24 h and 48 h,respectively,with an overall total of 70%7 d after surgery.No apparent signs of apoptotic cell death were detected in the extended hepatectomy rat livers,but hepatocytes displaying a clear cytoplasm and an accumulation of hyaline material testified to changes affecting their functional activities.Liver regeneration started properly,as early events initiating cell proliferation occurred within the first 3 h,and the G1 to S transition was detected in less than 12 h.However,a rise in p27(Kip1)followed by p21(Waf1/Cip1)cell cycle inhibitor levels led to a delayed S phase progression and mitosis.Overall,liver regeneration in rats with a 90%hepatectomy was delayed by 24 h and associated with a delayed onset and lower peak magnitude of hepatocellular deoxyribonucleic acid synthesis.CONCLUSION This work highlights the critical importance of the cyclin/cyclin-dependent kinase inhibitors of the Cip/Kip family in regulating the liver regeneration timeline following extended hepatectomy.

Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.

Adenine phosphoribosyltransferase deficiency: Leave no stone unturned

Adenine phosphoribosyltransferase(APRT)deficiency is a rare autosomal recessive disease leading to generation of large amounts of 2,8-dihydroxyadenine(DHA).DHA is excreted in urine,where it precipitates into crystals due to its low solubility.DHA crystals can aggregate into stones or cause injury to the renal parenchyma(DHA nephropathy).Recurrent urolithiasis and DHA nephropathy are the two clinical manifestations of APRT deficiency.Diagnosis of APRT deficiency can be made during childhood as well as adulthood.Diagnosis mainly relies on the recognition of DHA in stones or urine crystals.Measurement of APRT activity and genetic testing are useful for confirmation of diagnosis,for family screening and should be considered in difficult cases of urolithiasis or crystalline nephropathy.Allopurinol therapy is the cornerstone of treatment and is highly effective in preventing recurrence of stones and kidney disease.High fluid intake and dietary modifications are also recommended.Early diagnosis and treatment are of paramount importance to prevent renal damage.Unfortunately,diagnosis of APRT deficiency is often overlooked and irreversible renal failure still occurs in a substantial proportion of patients.Clinicians must be alert to the possibility of APRT deficiency and consider the appropriate diagnostic tests in certain cases.This review discusses the genetic and biochemical mechanisms of APRT deficiency,and the issues of diagnosis and management.

Postoperative Outcomes in Exploratory Laparotomy and Intestinal Resection in Children: A Secondary Descriptive Observational Analysis

Background: We previously reported independent predictors of intraoperative and postoperative morbidity. These were age, American Society of Anesthesiologists Score (ASA), emergency situations, surgery and transfusion. ASA was the independent predictor of mortality. We conducted a secondary analysis of this previous retrospective study in patients who underwent exploratory laparotomy and intestinal resection. Objectives: The objective was to describe intraoperative and postoperative outcomes in patients who underwent exploratory laparotomy and intestinal resection in the initial study and to present a research protocol for intraoperative and postoperative optimization. Methods: Secondary analysis of the initial study was used. The Ethics Committee approved the study. Results: There were 54 patients with a median age of 15.5 [0 - 172] months. Thirty-seven (68.5%) patients underwent intestinal resection, nine (16.7%) underwent exploratory laparotomy, and eight (16.8%) underwent laparotomy for volvulus. Fourteen (25.9%) patients had intraoperative and/or postoperative complications. Two (3.7%) patients had an intraoperative hemorrhagic shock. Two (3.7%) patients had a postoperative cardio-circulatory failure. Three (5.6%) had postoperative respiratory failure. One (1.8%) patient had postoperative multiple organ failure and neurologic failure. Three (5.6%) patients had postoperative abdominal sepsis. One (1.8%) patient had postoperative multiple organ sepsis and neuromeningeal sepsis. Four (7.4%) patients had postoperative pulmonary sepsis. Two (3.7%) had postoperative septicemia. Six (11.1%) patients had reoperations. Seventeen (31.5%) patients had an intraoperative transfusion. The in-hospital mortality rate was 3.7% in two patients. Conclusion: The number of patients with postoperative complications in this cohort was not negligible. We, therefore, elaborated a research protocol where intraoperative patient management will be guided with transthoracic echocardiography for fluid and hemodynamic therapy optimization. The objective of this study protocol is to clarify the impact of intraoperative goal-directed fluid and hemodynamic therapy with transthoracic echocardiography on postoperative outcomes in terms of complications in pediatric surgical patients.

Individual and Environmental Risk Factors for COVID-19 Mortality in Elderly in 7 European University Hospitals

Because the elderly account for 80% of deaths from COVID-19 and they may be more vulnerable to air pollution, in this retrospective study we aimed to explore individual and environmental risk factors for COVID-19 mortality in the geriatric departments of seven European University hospitals, between February and May 2020. Long-term exposure to air pollution was estimated through annual pollutant concentrations at the residential address over the last two years. Short-term variations in air pollutants and weather parameters were also examined through a 20-day period before the confirmed PCR diagnostic of COVID-19. We found positive associations for diabetes and COVID-19 mortality (OR 2.2 CI 95%: 1.1, 4.4). Regarding environmental factors, we found no association between COVID-19 mortality and air pollutants and weather parameters;however, our study suffers from strong disparities—such as patient characteristics—between fairly polluted and less polluted cities. In order to overcome those disparities between cities, we aimed to explore the relationship between air pollution and COVID-19 mortality within each city, but even with the high-efficiency modelisation systems, differences in air pollutants were too small to estimate the effect of air pollution at the city level. Thus, this study highlights the need to improve the estimation of individual exposure to air pollution. To address this issue, solutions exist such as the increase of the number of fixed air monitors, or even better, through the use of individual markers of air pollution exposure such as urinary black carbon or passive individual samplers. Furthermore, we underline that outdoor air pollutant concentrations may not be representative of individual exposure, especially in the elderly, thus, we suggest that further studies focus on indoor air pollution. Regarding meteorological conditions, we found no association between UV, temperature, wind speed and COVID-19 mortality. We found a positive association between an increase in relative humidity (RH) and COVID-19 mortality, however, the influence of RH on COVID-19 mortality remains unclear, and additional studies are needed to confirm this potential link.

Physical activity,COVID-19,and respiratory comorbidities:The good,the bad,and the ugly

Almost 3 years after the outbreak of the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)responsible for the coronavirus disease 2019(COVID-19)that has caused more than 6 million deaths worldwide,1the pandemic persists and hampers our daily lives.There are at least 2 main reasons explaining why we still struggle to terminate this pandemic.First,novel variants of concern of SARS-CoV-2unceasingly emerge despite almost 12 billion doses of vaccinebeing administered to date.