Keum Hwa Lee

Body mass index and 20 specific cancers: re-analyses of dose–response meta-analyses of observational studies

Background Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between body mass index (BMI) and risk of developing cancer. Methods We carried out an umbrella review and comprehensively re-analyzed the data of dose-response meta-analyses on associations between BMI and risk of 20 specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, esophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies. Convincing evidence for an association was defined as a strong statistical significance in fixed-effects and random-effects meta-analyses at P < 0.001, 95% prediction interval (PI) excluded null, there was no large between-study heterogeneity and no small study effects. Suggestive evidence was defined as meeting the significance threshold for the random summary effects of P < 0.05, but 95% PI included the null. Weak evidence was defined as meeting the significance threshold for the random summary effects at a P < 0.05, but 95% PI included the null and there was large between-study heterogeneity or there were small study effects. Results Convincing evidence for an association with BMI was detectable for six cancers (leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma). Suggestive evidence was detectable for malignant melanoma, non-Hodgkins lymphoma, and esophageal adenocarcinoma. Weak evidence was detectable for brain and central nervous system tumors, breast, colon, gall bladder, lung, liver, ovarian, and thyroid cancer. No evidence was detectable for bladder, gastric, and prostate cancer. Conclusions The association of increased BMI and cancer is heterogeneous across cancer types. Leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma are convincingly associated with an increased BMI by dose-response meta-analyses.

The value of delta neutrophil index in young infants with febrile urinary tract infection

Delta neutrophil index (DNI) is the fraction of circulating immature granulocytes, which reflects severe bacterial infections and septic condition but has not been studied in urinary tract infection (UTI). Here, we evaluated the value of DNI in predicting acute pyelonephritis (APN) or vesicoureteral reflux (VUR) using the data of 288 patients. Conventional inflammatory markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and DNI were measured. WBC, CRP, ESR and DNI were higher in APN than in lower UTI (p < 0.01). Multiple logistic-regression analyses showed that DNI was a predictive factor for areas of lack of uptake on dimercaptosuccinic acid (DMSA) scans (P < 0.01). The area under the receiver operating characteristic (AUC) was also high for DNI (0.622, 95% CI 0.558–0.687, P < 0.01) as well as for CRP (0.731, 95% CI 0.673–0.789, P < 0.01) for the prediction of DMSA defects. DNI demonstrated the highest area under the ROC curve for diagnosis of VUR (0.620, 95% CI 0.542–0.698, P < 0.01). To the best of our knowledge, this is a first study demonstrating that DNI can be used as a diagnostic marker to distinguish APN from lower UTI and function as a diagnostic marker indicative of VUR compared to other conventional markers.

Genetics of vesicoureteral reflux and congenital anomalies of the kidney and urinary tract

The definition of congenital anomalies of the kidney and urinary tract (CAKUT) is the disease of structural malformations in the kidney and/or urinary tract containing vesicoureteral reflux (VUR). These anomalies can cause pediatric chronic kidney disease. However, the pathogenesis of CAKUT is not well understood, because identifying the genetic architecture of CAKUT is difficult due to the phenotypic heterogeneity and multifactorial genetic penetrance. We describe the current genetic basis and mechanisms of CAKUT including VUR via approaching the steps and signaling pathways of kidney developmental processes. We also focus on the newly developed strategies and challenges to fully address the role of the associated genes in the pathogenesis of the disease.

Posterior nutcracker syndrome – a systematic review

Posterior nutcracker syndrome (PNCS) is the entrapment of the left renal vein between the aorta and the vertebral column. Although uncommon, it is still an important diagnosis due to the high morbidity associated with the risk of secondary anaemia from haematuria, from long-term left renal vein hypertension, vascular thrombosis, and even blood clots in the urinary system. A literature search of PubMed and EMBASE databases was performed and 27 publications containing 27 cases were included for the final analysis. The following frequency of clinical signs and symptoms was noted: twenty-five patients had haematuria, 13 patients had flank pain, and two had hypertension. Overall, male-female distribution was balanced and there were more adult than paediatric (age < 18 years) patients. All symptoms of patients with conservative treatment were either well-controlled or under spontaneous resolution. Conservative management instead of surgical treatment should be preferred in most cases. Taken together, despite the low incidence of PNCS, its recognition and management are highly important. This systematic study explores the evidence base for conservative and medical options.

Field Synopsis and Re-analysis of Systematic Meta-analyses of Genetic Association Studies in Multiple Sclerosis: a Bayesian Approach

To provide an up-to-date summary of multiple sclerosis-susceptible gene variants and assess the noteworthiness in hopes of finding true associations, we investigated the results of 44 meta-analyses on gene variants and multiple sclerosis published through December 2016. Out of 70 statistically significant genotype associations, roughly a fifth (21%) of the comparisons showed noteworthy false-positive rate probability (FPRP) at a statistical power to detect an OR of 1.5 and at a prior probability of 10−6 assumed for a random single nucleotide polymorphism. These associations (IRF8/rs17445836, STAT3/rs744166, HLA/rs4959093, HLA/rs2647046, HLA/rs7382297, HLA/rs17421624, HLA/rs2517646, HLA/rs9261491, HLA/rs2857439, HLA/rs16896944, HLA/rs3132671, HLA/rs2857435, HLA/rs9261471, HLA/rs2523393, HLA-DRB1/rs3135388, RGS1/rs2760524, PTGER4/rs9292777) also showed a noteworthy Bayesian false discovery probability (BFDP) and one additional association (CD24 rs8734/rs52812045) was also noteworthy via BFDP computation. Herein, we have identified several noteworthy biomarkers of multiple sclerosis susceptibility. We hope these data are used to study multiple sclerosis genetics and inform future screening programs.

Dapsone as a potential treatment option for Henoch-Schönlein Purpura (HSP)

Henoch-Schönlein Purpura (HSP, IgA vasculitis) is an immunoglobulin A (IgA) mediated disorder characterized by systemic vasculitis with variable presentation, frequently affecting the skin, mucous membrane, joints, kidneys, and rarely lungs and the central nervous system. Interestingly, enhanced production of interleukin-8 (IL-8) levels are found during active disease and increased levels have been reported in supernatants from human umbilical venous endothelial cells after stimulation with sera from patients affected by HSP. While corticosteroid therapy is currently the recommended treatment for HSP, dapsone, an anti-leprosy agent, has also recently been suggested to have therapeutic efficacy due to its ability to suppress IL-8. Moreover, in addition to IL-8 suppression, dapsone has been reported to exert various anti-inflammatory effects by inhibiting the generation of toxic free radicals, myeloperoxidase mediated halogenation that converts H2O2 to HOCl, leukocyte chemotaxis, production of tumor necrosis factor, and other anti-inflammatory molecules. This review aims to provide a solid hypothesis for the pathogenesis of vasculitis in HSP. Moreover, we highlight potential mechanistic actions of dapsone in hopes that dapsone may be considered as an alternative viable treatment for patients affected by HSP.