Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)globally.However,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated.This study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer settings.Methods:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each CPG.We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types.Results:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR A.Overall,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous versions.The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current version.In the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)recommendations.Significant variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer types.Conclusion:One-third of the current ESMO CPG recommendations are supported by the highest level of evidence.More well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

Mesenchymal Stem Cells (MSCs) as a Novel Therapeutic Option for nCOVID-19—A Review

The novel Coronavirus Disease (nCOVID-19) is a highly contagious viral infection which emerged as “Pneumonia of Unknown Etiology” at Hubei province of Wuhan city in China. The health authorities provided a considerable empirical evidence after this outbreak and it was notified that the causative virus, named Novel Coronavirus (subsequently SARS-CoV-2) is the culprit for progressively exerting grim effects not only on individual patients but also on the International public health, with high mutational tendencies. WHO declared nCOVID-19 as a Pandemic on 11th March 2020. The spike glycoprotein of SARS-CoV-2 plays a pivotal role in the entry of virus into the cell and it further interacts with ACE-II receptors which are widely distributed on the human cell surface especially on alveolar type II cells (AT-2) and endothelium. The mortality in nCOVID-19 patients is usually preceded by acute respiratory distress syndrome (ARDS) because of the cytokine storm. Advanced molecular biology and regenerative sciences renders a breakthrough in the treatment of severely ill nCOVID-19 patients with Mesenchymal Stem Cells (MSCs). Autologous or allogenic MSCs attenuate cytokine storm, improvise lung compliance, regulate inflammatory response, maintain functional alveoli microenvironment, promote endogenous regeneration and repair with no or minimal side effects. MSCs are naturally resistant to this novel Coronavirus. Even though it is corroborated with evidences from current clinical trials and pilot study, we emphasize the need for conducting more clinical trials with ethical consideration to prove the efficacy and safety of MSCs in combating nCOVID-19 infection and its complications.

Effects of anesthetic depth on postoperative pain and delirium:a meta-analysis of randomized controlled trials with trial sequential analysis

Background:Whether anesthetic depth affects postoperative outcomes remains controversial.This meta-analysis aimed to evaluate the effects of deepvs.light anesthesia on postoperative pain,cognitive function,recovery from anesthesia,complications,and mortality.Methods:PubMed,EMBASE,and Cochrane CENTRAL databases were searched until January 2022 for randomized controlled trials comparing deep and light anesthesia in adult surgical patients.The co-primary outcomes were postoperative pain and delirium(assessed using the confusion assessment method).We conducted a meta-analysis using a random-effects model.We assessed publication bias using the Begg’s rank correlation test and Egger’s linear regression.We evaluated the evidence using the trial sequential analysis and Grading of Recommendations Assessment,Development and Evaluation(GRADE)methodology.We conducted subgroup analyses for pain scores at different postoperative time points and delirium according to cardiac or non-cardiac surgery.Results:A total of 26 trials with 10,743 patients were included.Deep anesthesia compared with light anesthesia(a mean difference in bispectral index of-12 to-11)was associated with lower pain scores at rest at 0 to 1 h postoperatively(weighted mean difference=-0.72,95%confidence interval[CI]=-1.25 to-0.18,P=0.009;moderate-quality evidence)and an increased incidence of postoperative delirium(24.95%vs.15.92%;risk ratio=1.57,95%CI=1.28-1.91,P<0.0001;high-quality evidence).No publication bias was detected.For the exploratory secondary outcomes,deep anesthesia was associated with prolonged postoperative recovery,without affecting neurocognitive outcomes,major complications,or mortality.In the subgroup analyses,the deep anesthesia group had lower pain scores at rest and on movement during 24 h postoperatively,without statistically significant subgroup differences,and deep anesthesia was associated with an increased incidence of delirium after non-cardiac and cardiac surgeries,without statistically significant subgroup differences.Conclusions:Deep anesthesia reduced early postoperative pain but increased postoperative delirium.The current evidence does not support the use of deep anesthesia in clinical practice.

Are demographics associated with mucoepidermoid or acinic cell carcinoma parotid malignancies in children?

Objective:To identify possible associations between patient demographics and parotid cancer histological type in pediatric patients.Methods:Pediatric patients(ages:birth-18.0 years)in the Surveillance,Epidemiology,and End Results(SEER)database were included from 1973 to 2014 based on a diagnosis of mucoepidermoid carcinoma or acinic cell carcinoma of the parotid gland using the ICD O-3 codes of C07.9 and 8430 or 8550.Patients were classified into the following cohorts:<14 and 14-18 years of age based on the mean age at diagnosis.Results:Three hundred and three pediatric patients were diagnosed with mucoepidermoid carcinoma or acinic cell carcinoma of the parotid gland within the SEER 18 registries.Female pediatric patients 14-18 years of age were 7.68 times more likely to have an acinic cell carcinoma(adjusted OR:7.68[95%Cl:2.01-29.44]).When stratified by histological type,58.9%of female pediatric patients≥14 years of age had an acinic cell carcinoma as compared to 37.3%of male pediatric patients≥14 years of age,36.5%of female pediatric patients<14 years of age,and 34.0%of male pediatric patients<14 years of age(P=0.01).Conclusions:Based on this study,pediatric female patients between the ages of 14 and 18 years are the most likely cohort to have acinic cell carcinoma.The results of this study may assist providers during the work up of a pediatric patient with a suspected parotid malignancy.