Clinical Interventions and All-Cause Mortality of Patients with Chronic Kidney Disease: An Umbrella Systematic Review of Meta-Analyses

Patients with chronic kidney disease (CKD) have altered physiologic processes, which result in different treatment outcomes compared with the general population. We aimed to systematically evaluate the efficacy of clinical interventions in reducing mortality of patients with CKD. We searched PubMed, MEDLINE, Embase, and Cochrane Database of Systematic Reviews for meta-analyses of randomized controlled trials (RCT) or observational studies (OS) studying the effect of treatment on all-cause mortality of patients with CKD. The credibility assessment was based on the random-effects summary estimate, heterogeneity, 95% prediction intervals, small study effects, excess significance, and credibility ceilings. Ninety-two articles yielded 130 unique meta-analyses. Convincing evidence from OSs supported mortality reduction with three treatments: angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers for patients not undergoing dialysis, warfarin for patients with atrial fibrillation not undergoing dialysis, and (at short-term) percutaneous coronary intervention compared to coronary artery bypass grafting for dialysis patients. Two treatment comparisons were supported by highly credible evidence from RCTs in terms of all-cause mortality. These were high-flux hemodialysis (HD) versus low-flux HD as a maintenance HD method and statin versus less statin or placebo for patients not undergoing dialysis. Most significant associations identified in OSs failed to be replicated in RCTs. Associations of high credibility from RCTs were in line with current guidelines. Given the heterogeneity of CKD, it seems hard to assume mortality reductions based on findings from OSs.ope

Statin and Cancer Mortality and Survival: An Umbrella Systematic Review and Meta-Analysis

The aim of this study is to provide an overview and understand the strength of evidence and the extent of potential biases and the validity of claimed associations between the use of statins and cancer mortality or survival. We performed a comprehensive umbrella review of meta-analyses and systematically appraised the relevant meta-analyses of observational studies on the associations between statin use and cancer mortality or survival in various kinds of cancer. We searched the PubMed database and screened the reference list of relevant articles. We obtained the summary effect, 95% confidence interval, heterogeneity, and also examined small study effects and 95% prediction intervals for effect sizes, and the level of evidence was determined from the criteria. Regarding cancer mortality, statin use showed convincing evidence for an association with a reduced cancer-specific mortality rate for colorectal cancer. Four associations with reduced all-cause mortality (for breast cancer, colorectal cancer, endocrine-related gynecological cancer, and ovarian cancer) had a suggestive evidence. Moreover, analyses in nine cancers showed a weak level of evidence, while the remaining 15 did not indicate significant changes in either direction. Although there was a preventive effect of statin on cancer mortality in some cancer types, the evidence supporting the use of statins to reduce cancer mortality or survival was low.ope

Efficacy of Cancer Immunotherapy: An Umbrella Review of Meta-analyses of Randomized Controlled Trials

We conducted a systematic review for evidence of the clinical efficacy of cancer immunotherapies. We searched PubMed from inception to 14 February 2018 for meta-analyses of randomized controlled trials (RCTs) of cancer immunotherapies. Re-analyses were performed to estimate the summary effect size under random-effects, the 95% confidence interval (CI), heterogeneity, and the 95% prediction interval, and we determined the strength of the evidence. We examined publication bias and excess significance bias. 63 articles corresponding to 247 meta-analyses were eligible. Nine meta-analyses were classified to have convincing evidence, and 75 were classified as suggestive evidence. The clinical benefit of immunotherapy was supported by convincing evidence in the following settings: anti-PD-1/PD-L1 monoclonal antibody (mAb) therapy for treating advanced melanoma and non-small cell lung cancer (NSCLC), the combination of rituximab and chemotherapy for treating chronic lymphocytic leukemia and B-cell non-Hodgkin's lymphoma, adoptive cell immunotherapy for NSCLC, and the combination of interferon α and chemotherapy for metastatic melanoma. A further meta-analysis of 16 RCTs showed that anti-PD-1/PD-L1 mAb therapy had a benefit in patients with solid tumors (overall survival; hazard ratio = 0.73, 95% CI: 0.68-0.79; p < 0.001), supported by convincing evidence. In the future, rigorous approaches are needed when interpreting meta-analyses to gain better insight into the true efficacy of cancer immunotherapy.ope

Imperforate Hymen: A Comprehensive Systematic Review

Imperforate hymen (IH) is an uncommon congenital anomaly of the female genital tract, with the hymen completely obstructing the vaginal opening. Despite the simple diagnosis and treatment of IH, missed or delayed diagnosis is often a clinical problem owing to its low incidence, nonspecific symptoms, or insufficient physical examination. The aim of this study is to identify the characteristics, clinical presentations, treatment modalities, and outcomes of imperforate hymen patients. In this study, a literature search of PubMed, Scopus and Medline databases was performed for sources published up to 3 July 2018 for English-language studies with the term "imperforate hymen". The literature review identified 251 citations and 155 articles (143 case reports, 12 case series) containing 253 patients who were finally included (two papers were not written in English). Among 236 postnatal patients, the mean age of the patients was 10.7 ± 4.7 years. Abdominal pain (54.2%), urinary retention (20.3%), abnormal menstruation (14.0%), dysuria (9.7%), increased urinary frequency (5.1%), severe presentation of renal failure (n = 5, 2.1%), and urinary tract infection (n = 1, 0.4%) were presented. Most patients diagnosed with the condition underwent surgical treatment (83.5%), most of whom were treated via a hymenotomy (35.2%) and hymenectomy (36.4%), and the use of prophylactic antibiotics were only used in 7 patients. There were no differences in outcomes between two surgical methods. In addition, 141 (59.7%) patients showed improvement and 5 deceased patients were not related to IH or the operation itself; Complications, such as vaginal adhesion, were only noted in 6.6% of patients. In addition, among 17 cases of newborns with a diagnosis of IH before birth, hymenectomy (n = 5, 29.4%) and hymenotomy (n = 9, 52.9%) were the main treatment modalities and showed improved prognosis in 52.9% of newborns. Because IH diagnosis is easy and postsurgical prognosis is good, clinicians should carefully examine every female patient at birth. IH should be considered regarding adolescent girls with abdominal pain, lower back pain, or urinary retention, and perform appropriate physical examinations of the genital introitus. In addition, accurate diagnosis as IH, not misdiagnosing as vaginal septum or agenesis, is important to prevent severe complications such as stricture and ascending infection.ope

Predictive factors for bacteremia in febrile infants with urinary tract infection

This study aimed to investigate the predictive factors of concomitant bacteremia occurring in febrile infants who initially presented with pyuria and fever, and were subsequently diagnosed with culture-proven urinary tract infection (UTI). We conducted a retrospective cohort study for January 2010-October 2018 that included infants younger than six months with febrile UTI at a tertiary hospital. The study included 463 patients, of whom 34 had a concomitant bacteremic UTI. Compared to those in the non-bacteremic urinary tract infection (UTI) group, the bacteremic UTI group had a lower mean age; higher levels of C-reactive protein (CRP), delta neutrophil index (DNI, reflects the fraction of immature granulocytes) and blood urea nitrogen (BUN); lower levels of hemoglobin (Hb) and albumin; and a lower platelet count. Vesicoureteral reflux (VUR) was detected nearly twice as often in patients with bacteremic UTI compared to those with non-bacteremic UTI (59.3% vs. 30.6%; P = 0.003). Univariate logistic analyses showed that age ≤90 days; higher DNI, CRP, and creatinine levels; lower Hb and albumin levels; and the presence of VUR were predictors for bacteremic UTI. On multivariate logistic regression analysis, age ≤90 days, higher DNI and CRP levels, and the presence of VUR were independent predictors of bacteremic UTI. The area under the receiver operating characteristic curve of the multivariate model was 0.859 (95% CI, 0.779-0.939; P < 0.001). Age ≤90 days, higher DNI and CRP values may help predict bacteremia of febrile infants younger than 6 months with UTI. Vesicoureteral reflux imaging is also recommended in infants with bacteremic UTI to evaluate VUR.ope

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.ope

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

Interleukin-4 (IL-4) expression is implicated in the pathogenesis of nephrotic syndrome (NS). This study aimed to investigate the changes in the transcriptomes of human podocytes induced by IL-4 treatment and to analyze whether these changes could be affected by simultaneous steroid treatment. Three groups of human podocytes were treated with control, IL-4, and IL-4 plus dexamethasone (DEX), respectively. We performed whole-transcriptome sequencing to identify differentially expressed genes (DEGs) between the groups. We investigated relevant biological pathways using Gene Ontology (GO) enrichment analyses. We also attempted to compare and validate the DEGs with the genes listed in PodNet, a literature-based database on mouse podocyte genes. A total of 176 genes were differentially expressed among the three groups. GO analyses showed that pathways related to cytoskeleton organization and cell signaling were significantly enriched. Among them, 24 genes were listed in PodNet, and 12 of them were previously reported to be associated with IL-4-induced changes in human podocytes. Of the 12 genes, the expression levels of BMP4, RARB, and PLCE1 were reversed when podocytes were simultaneously treated with DEX. In conclusion, this study explored changes in the transcriptome profiles of human podocytes treated with IL-4. Few genes were reported in previous studies and were previously validated in experiments with human podocytes. We speculate that IL-4 may exert pathogenic effects on the transcriptome of human podocytes, and a few genes may be involved in the pathogenesis.ope

A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era

Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.ope

Characteristics of pediatric rhabdomyolysis and the associated risk factors for acute kidney injury: a retrospective multicenter study in Korea

Background: The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods: This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results: Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions: Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.ope

Therapeutic Plasma Exchange in Pediatric Kidney Disease: 23-year Experience at the Severance Children's Hospital in Korea

Purpose: The American Society for Apheresis provides clinical guidelines for therapeutic apheresis in adults, but there are no guidelines for children. This study aimed to analyze the effect of therapeutic plasma exchange (TPE) in pediatric patients with various kidney diseases in Korea. Methods: We retrospectively reviewed the data of 16 children (up to 18 years of age) who were admitted to Severance Children's Hospital with refractory kidney disease. All patients received TPE between 1994 and 2016. Clinical and laboratory characteristics such as age, weight, sex, change in blood urea nitrogen (BUN), and creatinine level before and after TPE, and complications after TPE were analyzed. Results: The mean age and weight of the 16 patients at the time of TPE was $11.3{\pm}4.0$ years and $34.6{\pm}17.5$ kg, respectively. The BUN level was 35.4 mg/dL before TPE and significantly decreased to 21.5 mg/dL (P=0.025) at 1 week and 20.5 mg/dL (P= 0.01) at 1 month after TPE. The creatinine level significantly decreased from 1.20 mg/dL before TPE to 0.90 mg/dL (P=0.02) at 1 week after TPE. Four complications (hypovolemia, anemia, hypocalcemia, and thrombocytopenia) were reported, but were not fatal. Conclusion: Our findings suggest that TPE is an effective therapeutic modality in children with refractory kidney disease and can be indicated for the treatment of various kidney diseases.ope