Hyperprogressive Disease during Anti-PD-1 (PDCD1) / PD-L1 (CD274) Therapy: A Systematic Review and Meta-Analysis

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

Sarcopenia in autoimmune and rheumatic diseases: a comprehensive review

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia

A Review of Pre-Exposure Prophylaxis Adherence among Female Sex Workers

Globally and in Africa specifically, female sex workers (FSWs) are at an extraordinarily high risk of contracting HIV. Pre-exposure prophylaxis (PrEP) has emerged as an effective and ethical method with which to prevent HIV infection among FSWs. PrEP efficacy is, however, closely linked to adherence, and adherence to PrEP among FSWs is a complex and interrelated process that has been shown to be of importance to public health policies and HIV control and intervention programs. This comprehensive review categorizes barriers to and facilitators of adherence to human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) for FSWs, and describes five strategies for promoting PrEP adherence among FSWs. These strategies encompass (1) a long-term educational effort to decrease the stigma associated with sex work and PrEP use, (2) education on how PrEP works, (3) lifestyle modification, (4) research on next-generation PrEP products to address the inconvenience of taking daily pills, and (5) integration of PrEP into existing services, such as social services and routine primary care visits, to reduce the economic burden of seeking the medication. Our review is expected to be useful for the design of future PrEP intervention programs. Multidisciplinary intervention should be considered to promote PrEP adherence among FSWs in order to help control the HIV epidemic

Epidemiology, Transmission, Risk Factors, and International Responses of Coronavirus Disease 2019: A Comprehensive Review

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide pandemic. The first reports of patients with COVID-19 were provided to World Health Organization on December 21, 2019 and were presumably associated with seafood markets in Wuhan, China. As of October 25, 2020, more than 42 million cases have been confirmed worldwide, with more than 1.1 million deaths. Asymptomatic transmission contributes significantly to transmission, and clinical features are non-specific to the disease. Thus, the diagnosis of COVID-19 requires specific viral RNA testing. The disease demonstrates extensive human-to-human transmissibility and has infected healthcare workers at high rates. Clinical awareness of the epidemiology and the risk factors for nosocomial transmission of COVID-19 is essential to preventing infection. Moreover, effective control measures should be further identified by comprehensive evaluation of hospital and community responses. In this review, we provide a comprehensive update on the epidemiology, presentation, transmission, risk factors, and public health measures associated with COVID-19. We also review past insights from previous coronavirus epidemics [i.e., severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)] to suggest measures to reduce transmission

Incidence of Capillary Leak Syndrome as an Adverse Effect of Drugs in Cancer Patients: A Systematic Review and Meta-Analysis

Capillary leak syndrome (CLS) is a rare disease with profound vascular leakage, which can be associated with a high mortality. There have been several reports on CLS as an adverse effect of anti-cancer agents and therapy, but the incidence of CLS according to the kinds of anti-cancer drugs has not been systemically evaluated. Thus, the aim of our study was to comprehensively meta-analyze the incidence of CLS by different types of cancer treatment or after bone marrow transplantation (BMT). We searched the literatures (inception to July 2018) and among 4612 articles, 62 clinical trials (studies) were eligible. We extracted the number of patients with CLS, total cancer patients, name of therapeutic agent and dose, and type of cancer. We performed a meta-analysis to estimate the summary effects with 95% confidence interval and between-study heterogeneity. The reported incidence of CLS was categorized by causative drugs and BMT. The largest number of studies reported on CLS incidence during interleukin-2 (IL-2) treatment (n = 18), which yielded a pooled incidence of 34.7% by overall estimation and 43.9% by meta-analysis. The second largest number of studies reported on anti-cluster of differentiation (anti-CD) agents (n = 13) (incidence of 33.9% by overall estimation and 35.6% by meta-analysis) or undergoing BMT (n = 7 (21.1% by overall estimation and 21.7% by meta-analysis). Also, anti-cancer agents, including IL-2 + imatinib mesylate (three studies) and anti-CD22 monoclinal antibodies (mAb) (four studies), showed a dose-dependent increase in the incidence of CLS. Our study is the first to provide an informative overview on the incidence rate of reported CLS patients as an adverse event of anti-cancer treatment. This meta-analysis can lead to a better understanding of CLS and assist physicians in identifying the presence of CLS early in the disease course to improve the outcome and optimize management

Environmental risk factors and biomarkers for autism spectrum disorder:an umbrella review of the evidence

Background Numerous studies have identified potential risk factors and biomarkers for autism spectrum disorder. We aimed to study the strength and validity of the suggested environmental risk factors or biomarkers of autism spectrum disorder. Methods We did an umbrella review and systematically appraised the relevant meta-analyses of observational studies. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for papers published between database inception and Oct 17, 2018, and screened the reference list of relevant articles. We obtained the summary effect, 95% CI, heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We did analyses under credibility ceilings. This review is registered with PROSPERO, number CRD42018091704. Findings 46 eligible articles yielded data on 67 environmental risk factors (544 212 cases, 81 708 787 individuals) and 52 biomarkers (15 614 cases, 15 433 controls). Evidence of association was convincing for maternal age of 35 years or over (relative risk [RR] 1.31, 95% CI 1.18-1.45), maternal chronic hypertension (odds ratio [OR] 1.48, 1.29-1.70), maternal gestational hypertension (OR 1.37, 1.21-1.54), maternal overweight before or during pregnancy (RR 1.28, 1.19-1.36), pre-eclampsia (RR 1.32, 1.20-1.45), prepregnancy maternal antidepressant use (RR 1.48, 1.29-1.71), and maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy (OR 1.84, 1.60-2.11). Only two associations, maternal overweight before or during pregnancy and SSRI use during pregnancy, retained their high level of evidence under subset sensitivity analyses. Evidence from biomarkers was scarce, being supported by p values close to the significance threshold and too few cases. Interpretation Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome, are associated with risk of autism spectrum disorder. Although SSRI use during pregnancy was also associated with such risk when exposed and non-exposed groups were compared, this association could be affected by other confounding factors, considering that prepregnancy maternal antidepressant use was also convincingly associated with higher risk of autism spectrum disorder. Findings from previous studies suggest that one possible confounding factor is underlying maternal psychiatric disorders. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Funding Agencies|Health Education England [ICA-CL-2017-03-001]; National Institute for Health Research (NIHR) [ICA-CL-2017-03-001]; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust; Maudsley Charity; Kings College London; NIHR South London Collaboration for Leadership in Applied Health Research and Care</p

Public Interest in Immunity and the Justification for Intervention in the Early Stages of the COVID-19 Pandemic: Analysis of Google Trends Data

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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

Clinical characteristics and mortality of patients with hematologic malignancies and COVID-19: a systematic review

OBJECTIVE: Hematologic cancer patients with Coronavirus Disease 2019 (COVID-19) tend to have a more serious disease course than observed in the general population. Herein, we comprehensively reviewed existing literature and analyzed clinical characteristics and mortality of patients with hematologic malignancies and COVID-19. MATERIALS AND METHODS: Through searching PubMed until June 03, 2020, we identified 16 relevant case studies (33 cases) from a total of 45 studies that have reported on patients with COVID-19 and hematologic malignancies. We investigated the clinical and laboratory characteristics including type of hematologic malignancies, initial symptoms, laboratory findings, and clinical outcomes. Then, we compared those characteristics and outcomes of patients with hematologic malignancies and COVID-19 to the general population infected with COVID-19. RESULTS: The median age was 66-year-old. Chronic lymphocytic leukemia was the most common type of hematologic malignancy (39.4%). Fever was the most common symptom (75.9%). Most patients had normal leukocyte counts (55.6%), lymphocytosis (45.4%), and normal platelet counts (68.8%). In comparison to patients with COVID-19 without underlying hematologic malignancies, dyspnea was more prevalent (45.0 vs. 24.9%, p=0.025). Leukocytosis (38.9 vs. 9.8%, p=0.001), lymphocytosis (45.4 vs. 8.2%, p=0.001), and thrombocytopenia (31.3 vs. 11.4%, p=0.036) were significantly more prevalent and lymphopenia (18.2 vs. 57.4%, p=0.012) less prevalent in patients with hematologic malignancies. There were no clinical and laboratory characteristics predicting mortality in patients with hematologic malignancies. Mortality was much higher in patients with hematologic malignancies compared to those without this condition (40.0 vs. 3.6%, p<0.001). CONCLUSIONS: Co-occurrence of hematologic malignancies and COVID-19 is rare. However, due to the high mortality rate from COVID-19 in this vulnerable population, further investigation on tailored treatment and management is required

Hypocomplementemia (C3) as an Independent Predictor for Children with Acute Post-streptococcal Glomerulonephritis: A Long-Term Observation

OBJECTIVE: The aim of this study was to examine the altering patterns in clinical characteristics and severity of acute post-streptococcal glomerulonephritis (APSGN) in children. PATIENTS AND METHODS: We analyzed the medical records of 119 children who were diagnosed with APSGN from 1987 to 2018, retrospectively. The patients were divided into two groups: Group I (n=72, before 1998) and Group II (n=47, after 1998). Clinical, radiologic, and laboratory findings were compared between the two groups. RESULTS: The clinical manifestations, including vomiting (20.8% vs. 4.3%, p=0.014), oliguria (40.3% vs. 19.1%, p=0.016), and generalized edema (86.1% vs. 63.8%, p=0.005), were statistically less frequent since 1998. Pulmonary edema on chest X-ray (22.7% vs. 4.4%, p=0.014) was less frequent in Group II than in Group I. The level of BUN (23.3±19.3 vs. 18.8±11.2, p=0.009) was lower in Group II than in Group I, while that of creatinine was not significantly different between the two groups. C3 level was an independent factor for predicting the development of edema (odds ratio [OR]: 1.034, 95% CI: 1.010-1.060, p=0.006) and acute nephritic symptoms (≥2) (OR: 0.974, 95% CI: 0.952-0996, p=0.020). It was also negatively correlated with an increasing number of acute nephritic symptoms, including oliguria and edema, in patients with APSGN (R=−0.182, p=0.048). CONCLUSIONS: This study demonstrated that APSGN had favorable clinical manifestations and severity over the past 30 years. The monitoring of C3 levels can be used to assess the disease severity and risk of complications, including edema and oliguria, which are decreasing in South Korean children

Estimation of global case fatality rate of coronavirus disease 2019 (COVID-19) using meta-analyses: Comparison between calendar date and days since the outbreak of the first confirmed case

Objective: Since the outbreak of the coronavirus disease 2019 (COVID-19) in December of 2019 in China, the estimation of the pandemic’s case fatality rate (CFR) has been the focus and interest of many stakeholders. In this manuscript, we prove that the method of using the cumulative CFR is static and does not reflect the trend according to the daily change per unit of time. Methods: A proportion meta-analysis was carried out on CFR in every country reporting COVID-19 cases. Based on the results, we performed a meta-analysis for global COVID-19 CFR. Each analysis was performed on two different calculations of CFR: according to calendar date and according to days since the outbreak of the first confirmed case. We thus explored an innovative and original calculation of CFR concurrently based on the date of the first confirmed case as well as on a daily basis. Results: For the first time, we showed that using meta-analyses, according to calendar date and days since the outbreak of the first confirmed case were different. Conclusion: We propose that CFR according to days since the outbreak of the first confirmed case might be a better predictor of the current CFR of COVID-19 and its kinetics