Explore the vast range of titles available.

PurposeTo determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea.MethodsData regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020.ResultsOut of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500–1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses.ConclusionAdults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.

Tumor mutational burden (TMB) is a genomic biomarker that predicts favorable responses to immune checkpoint inhibitors (ICIs). Here, we set out to assess the predictive value of TMB on long-term survival outcomes in patients undergoing ICIs. We systematically searched PubMed, Embase, CENTRAL and clinicaltrials.gov from inception to 6 August 2019. We included retrospective studies or clinical trials of ICIs that reported hazard ratios (HRs) for overall survival (OS) and/or progression-free survival (PFS) according to TMB. Data on 5712 patients from 26 studies were included. Among patients who received ICIs, high TMB groups showed better OS (HR 0.53, 95% CI 0.42 to 0.67) and PFS (HR 0.52, 95% CI 0.40 to 0.67) compared to low TMB groups. In patients with high TMB, those who received ICIs had a better OS (HR 0.69, 95% CI 0.50 to 0.95) and PFS (HR = 0.66, 95% CI = 0.47 to 0.92) compared to those who received chemotherapy alone, while in patients with low TMB, such ICI benefits of OS or PFS were not statistically significant. In conclusion, TMB may be an effective biomarker to predict survival in patients undergoing ICI treatment. The role of TMB in identifying patient groups who may benefit from ICIs should be determined in future randomized controlled trials.

Alzheimer’s disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs’ expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.

Hyperprogressive disease (HPD) is a recently acknowledged pattern of rapid tumor progression after the initiation of immune checkpoint inhibitors. HPD has been observed across various types of tumors and has been associated with poor survival. We performed a meta-analysis to identify baseline (i.e., prior to programmed cell death 1 [PD-1, PDCD1] / programmed cell death 1 ligand 1 [PD-L1, CD274] inhibitor therapy) patient factors associated with risks of developing HPD during PD-1/PD-L1 inhibitor therapy. We searched eight databases until 6 June 2019. We calculated the summary odds ratio (OR) and its 95% confidence interval (CI) using the random-effects model and explored between-study heterogeneity and small-study effects. A total of nine articles was eligible (217 HPD cases, 1519 cancer patients) for meta-analysis. There was no standard definition of HPD, and the incidence of HPD ranged from 1 to 30%. We identified twenty-three baseline patient factors, of which five factors were statistically significantly associated with HPD. These were serum lactate dehydrogenase (LDH) above the upper normal limit (OR = 1.89, 95% CI = 1.02–3.49, p = 0.043), more than two metastatic sites (OR = 1.86, 1.34–2.57, p < 0.001), liver metastases (OR = 3.33, 2.07–5.34, p < 0.001), Royal Marsden Hospital prognostic score of 2 or above (OR = 3.33, 1.96–5.66, p < 0.001), and positive PD-L1 expression status that was inversely correlated with HPD (OR = 0.60, 0.36–0.99, p = 0.044). Between-study heterogeneity was low. Evidence of small-study effect was found in one association (PD-L1 expression). Subset analyses of patients with non-small cell lung cancer showed similar results. Future studies are warranted to identify underlying molecular mechanisms and to test their roles as predictive biomarkers of HPD.

(1) Background: The global threat of Coronavirus disease 2019 (COVID-19) continues. The diversity of clinical characteristics and progress are reported in many countries as the duration of the pandemic is prolonged. We aimed to perform a novel systematic review and meta-analysis focusing on findings about correlations between clinical characteristics and laboratory features of patients with COVID-19. (2) Methods: We analyzed cases of COVID-19 in different countries by searching PubMed, Embase, Web of Science databases and Google Scholar, from the early stage of the outbreak to late March. Clinical characteristics, laboratory findings, and treatment strategies were retrospectively reviewed for the analysis. (3) Results: Thirty-seven (n = 5196 participants) COVID-19-related studies were eligible for this systematic review and meta-analysis. Fever, cough and fatigue/myalgia were the most common symptoms of COVID-19, followed by some gastrointestinal symptoms which are also reported frequently. Laboratory markers of inflammation and infection including C-reactive protein (CRP) (65% (95% confidence interval (CI) 56–81%)) were elevated, while lymphocyte counts were decreased (63% (95% CI 47–78%)). Meta-analysis of treatment approaches indicated that three modalities of treatment were predominantly used in the majority of patients with a similar prevalence, including antiviral agents (79%), antibiotics (78%), and oxygen therapy (77%). Age was negatively correlated with number of lymphocytes, but positively correlated with dyspnea, number of white blood cells, neutrophils, and D-dimer. Chills had been proved to be positively correlated with chest tightness, lung abnormalities on computed tomography (CT) scans, neutrophil/lymphocyte/platelets count, D-dimer and CRP, cough was positively correlated with sputum production, and pulmonary abnormalities were positively correlated with CRP. White blood cell (WBC) count was also positively correlated with platelet counts, dyspnea, and neutrophil counts with the respective correlations of 0.668, 0.728, and 0.696. (4) Conclusions: This paper is the first systematic review and meta-analysis to reveal the relationship between various variables of clinical characteristics, symptoms and laboratory results with the largest number of papers and patients until now. In elderly patients, laboratory and clinical characteristics indicate a more severe disease course. Moreover, treatments such as antiviral agents, antibiotics, and oxygen therapy which are used in over three quarters of patients are also analyzed. The results will provide “evidence-based hope” on how to manage this unanticipated and overwhelming pandemic.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.

The use of social big data is an important emerging concern in public health. Internet search volumes are useful data that can sensitively detect trends of the public's attention during a pandemic outbreak situation.BACKGROUNDThe use of social big data is an important emerging concern in public health. Internet search volumes are useful data that can sensitively detect trends of the public's attention during a pandemic outbreak situation.Our study aimed to analyze the public's interest in COVID-19 proliferation, identify the correlation between the proliferation of COVID-19 and interest in immunity and products that have been reported to confer an enhancement of immunity, and suggest measures for interventions that should be implemented from a health and medical point of view.OBJECTIVEOur study aimed to analyze the public's interest in COVID-19 proliferation, identify the correlation between the proliferation of COVID-19 and interest in immunity and products that have been reported to confer an enhancement of immunity, and suggest measures for interventions that should be implemented from a health and medical point of view.To assess the level of public interest in infectious diseases during the initial days of the COVID-19 outbreak, we extracted Google search data from January 20, 2020, onward and compared them to data from March 15, 2020, which was approximately 2 months after the COVID-19 outbreak began. In order to determine whether the public became interested in the immune system, we selected coronavirus, immune, and vitamin as our final search terms.METHODSTo assess the level of public interest in infectious diseases during the initial days of the COVID-19 outbreak, we extracted Google search data from January 20, 2020, onward and compared them to data from March 15, 2020, which was approximately 2 months after the COVID-19 outbreak began. In order to determine whether the public became interested in the immune system, we selected coronavirus, immune, and vitamin as our final search terms.The increase in the cumulative number of confirmed COVID-19 cases that occurred after January 20, 2020, had a strong positive correlation with the search volumes for the terms coronavirus (R=0.786; P<.001), immune (R=0.745; P<.001), and vitamin (R=0.778; P<.001), and the correlations between variables were all mutually statistically significant. Moreover, these correlations were confirmed on a country basis when we restricted our analyses to the United States, the United Kingdom, Italy, and Korea. Our findings revealed that increases in search volumes for the terms coronavirus and immune preceded the actual occurrences of confirmed cases.RESULTSThe increase in the cumulative number of confirmed COVID-19 cases that occurred after January 20, 2020, had a strong positive correlation with the search volumes for the terms coronavirus (R=0.786; P<.001), immune (R=0.745; P<.001), and vitamin (R=0.778; P<.001), and the correlations between variables were all mutually statistically significant. Moreover, these correlations were confirmed on a country basis when we restricted our analyses to the United States, the United Kingdom, Italy, and Korea. Our findings revealed that increases in search volumes for the terms coronavirus and immune preceded the actual occurrences of confirmed cases.Our study shows that during the initial phase of the COVID-19 crisis, the public's desire and actions of strengthening their own immune systems were enhanced. Further, in the early stage of a pandemic, social media platforms have a high potential for informing the public about potentially helpful measures to prevent the spread of an infectious disease and provide relevant information about immunity, thereby increasing the public's knowledge.CONCLUSIONSOur study shows that during the initial phase of the COVID-19 crisis, the public's desire and actions of strengthening their own immune systems were enhanced. Further, in the early stage of a pandemic, social media platforms have a high potential for informing the public about potentially helpful measures to prevent the spread of an infectious disease and provide relevant information about immunity, thereby increasing the public's knowledge.

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID‐19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV‐ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC‐CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug‐induced CV‐ADRs from COVID‐19 effects, we restricted analyses to patients with COVID‐19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC‐CMs in time‐ and dose‐dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.

Background and objectives: Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. Materials and Methods: We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Conclusions: Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.