A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice

Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. Methods: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Results: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Conclusion: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

Risk of ventricular tachycardia and its outcomes in patients undergoing continuous renal replacement therapy due to acute kidney injury

Despite efforts to treat critically ill patients who require continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI), their mortality risk remains high. This condition may be attributable to complications of CRRT, such as arrhythmias. Here, we addressed the occurrence of ventricular tachycardia (VT) during CRRT and its relationship with patient outcomes. Methods: This study retrospectively enrolled 2,397 patients who started CRRT due to AKI from 2010 to 2020 at Seoul National University Hospital in Korea. The occurrence of VT was evaluated from the initiation of CRRT until weaning from CRRT. The odds ratios (ORs) of mortality outcomes were measured using logistic regression models after adjustment for multiple variables. Results: VT occurred in 150 patients (6.3%) after starting CRRT. Among them, 95 cases were defined as sustained VT (i.e., lasting ≥30 seconds), and the other 55 cases were defined as non-sustained VT (i.e., lasting <30 seconds). The occurrence of sustained VT was associated with a higher mortality rate than a nonoccurrence (OR, 2.04 and 95% confidence interval [CI], 1.23–3.39 for the 30- day mortality; OR, 4.06 and 95% CI, 2.04–8.08 for the 90-day mortality). The mortality risk did not differ between patients with non-sustained VT and nonoccurrence. A history of myocardial infarction, vasopressor use, and certain trends of blood laboratory findings (such as acidosis and hyperkalemia) were associated with the subsequent risk of sustained VT. Conclusion: Sustained VT occurrence after starting CRRT is associated with increased patient mortality. The monitoring of electrolytes and acid-base status during CRRT is essential because of its relationship with the risk of VT.

Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study

Background@#The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function. @*Methods@#Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed. @*Results@#Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to –1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated. @*Conclusion@#Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.

Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis via the AKT/mTOR/NRF2 Signaling in Kidney Injury and Fibrosis

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

Growth Responses During 3 Years of Growth Hormone Treatment in Children and Adolescents With Growth Hormone Deficiency: Comparison Between Idiopathic, Organic and Isolated Growth Hormone Deficiency, and Multiple Pituitary Hormone Deficiency

Background@#The study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD). @*Methods@#Total 163 patients aged 2–18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment. @*Results@#The baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS.The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups.Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment. @*Conclusion@#The 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.

Classification of Mouse Lung Metastatic Tumor with Deep Learning

Traditionally, pathologists microscopically examine tissue sections to detect pathological lesions; the many slides that must be evaluated impose severe work burdens. Also, diagnostic accuracy varies by pathologist training and experience; better diagnostic tools are required. Given the rapid development of computer vision, automated deep learning is now used to classify microscopic images, including medical images. Here, we used a Inception-v3 deep learning model to detect mouse lung metastatic tumors via whole slide imaging (WSI); we cropped the images to 151 by 151 pixels. The images were divided into training (53.8%) and test (46.2%) sets (21,017 and 18,016 images, respectively). When images from lung tissue containing tumor tissues were evaluated, the model accuracy was 98.76%. When images from normal lung tissue were evaluated, the model accuracy (“no tumor”) was 99.87%. Thus, the deep learning model distinguished metastatic lesions from normal lung tissue. Our approach will allow the rapid and accurate analysis of various tissues.

Thyroid Dyshormonogenesis Due to Dual Oxidase Maturation Factor 2 Mutation as Non-Transient Status of Hypothyroidism

Dual oxidase maturation factor 2 (DUOXA2) is necessary for the enzymatic activity of dual oxidase 2 (DUOX2) to generate hydrogen peroxide production during thyroid hormone synthesis. We describe two Korean children, who were initially suspected to have transient congenital hypothyroidism (CH), but later confirmed to have permanent CH caused by DUOXA2 mutation. Treatment with levothyroxine was discontinued after confirming thyroid-stimulating hormone (TSH) level to be below 10 μU/mL and normal thyroid scan at the first or second trial-off therapy. However, after therapy cessation, TSH elevated to more than 10 μU/mL, and goiter developed in case 2. As a result, levothyroxine was resumed. Next-generation sequencing showed compound heterozygous mutations of DUOXA2 at Y138X and Y246X in case 1 and homozygous mutations of DUOXA2 at Y246X in case 2. In this report, a longer follow-up is recommended even after treatment termination in transient CH, and genetic studies might help assess the permanence of hypothyroidism in cases of mildly elevated TSH after trial-off therapy.

System of integrating biosignals during hemodialysis: the CONTINUAL (Continuous mOnitoriNg viTal sIgNdUring hemodiALysis) registry

Appropriate monitoring of intradialytic biosignals is essential to minimize adverse outcomes because intradialytic hypotension and arrhythmia are associated with cardiovascular risk in hemodialysis patients. However, a continuous monitoring system for intradialytic biosignals has not yet been developed. Methods: This study investigated a cloud system that hosted a prospective, open-source registry to monitor and collect intradialytic biosignals, which was named the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry. This registry was based on real-time multimodal data acquisition, such as blood pressure, heart rate, electrocardiogram, and photoplethysmogram results. Results: We analyzed session information from this system for the initial 8 months, including data for some cases with hemodynamic complications such as intradialytic hypotension and arrhythmia. Conclusion: This biosignal registry provides valuable data that can be applied to conduct epidemiological surveys on hemodynamic complications during hemodialysis and develop artificial intelligence models that predict biosignal changes which can improve patient outcomes.

Additive harmful effects of acute kidney injury and acute heart failure on mortality in hospitalized patients

Organ crosstalk between the kidney and the heart has been suggested. Acute kidney injury (AKI) and acute heart failure (AHF) are well-known independent risk factors for mortality in hospitalized patients. This study aimed to investigate if these conditions have an additive effect on mortality in hospitalized patients, as this has not been explored in previous studies. Methods: We retrospectively reviewed the records of 101,804 hospitalized patients who visited two tertiary hospitals in the Republic of Korea over a period of 5 years. AKI was diagnosed using serum creatinine-based criteria, and AHF was classified using International Classification of Diseases codes within 2 weeks after admission. Patients were divided into four groups according to the two conditions. The primary outcome was all-cause mortality. Results: AKI occurred in 6.8% of all patients (n = 6,920) and AHF in 1.2% (n = 1,244). Three hundred thirty-one patients (0.3%) developed both conditions while AKI alone was present in 6,589 patients (6.5%) and AHF alone in 913 patients (0.9%). Among the 5,181 patients (5.1%) who died, 20.8% died within 1 month. The hazard ratio for 1-month mortality was 29.23 in patients with both conditions, 15.00 for AKI only, and 3.39 for AHF only. The relative excess risk of interaction was 11.85 (95% confidence interval, 2.43–21.27), and was more prominent in patients aged <75 years and those without chronic heart failure. Conclusion: AKI and AHF have a detrimental additive effect on short-term mortality in hospitalized patients.

Evolving outcomes of peritoneal dialysis: secular trends at a single large center over three decades

Background@#Peritoneal dialysis (PD) is improving as a renal replacement therapy for end-stage renal disease (ESRD) patients. We analyzed the main outcomes of PD over the last three decades at a single large-scale PD center with an established high-quality care system. @*Methods@#As a retrospective cohort study, we included participants (n = 1,203) who began PD between 1990 and 2019. Major PD-related outcomes were compared among the three 10-year cohorts. @*Results@#The 1,203 participants were 58.3% male with a mean age of 47.9 ± 13.8 years. The median PD treatment duration was 45 months (interquartile range, 19–77 months); 362 patients (30.1%) transferred to hemodialysis, 289 (24.0%) received kidney transplants, and 224 (18.6%) died. Overall, the 5- and 8-year adjust patient survival rates were 64% and 49%, respectively. Common causes of death included infection (n = 55), cardiac (n = 38), and cerebrovascular (n = 17) events. The 5- and 8-year technique survival rates were 77% and 62%, respectively, with common causes of technique failure being infection (42.3%) and solute/water clearance problems (22.7%). The 5-year patient survival significantly improved over time (64% for the 1990–1999 cohort vs. 93% for the 2010–2019 cohort). The peritonitis rate also substantially decreased over time, from 0.278 episodes/patient-year (2000–2004) to 0.162 episodes/patient-year (2015–2019). @*Conclusion@#PD is an effective treatment option for ESRD patients. There was a substantial improvement in the patient survival and peritonitis rates over time. Establishing adequate infrastructure and an effective system for high-quality PD therapy may be warranted to improve PD outcomes.

Closure of Petersen's Space Lowers the Incidence of Gastric Food Retention after Distal Gastrectomy with Gastrojejunostomy in Gastric Cancer Patients

Purpose@#Delayed gastric emptying usually manifests as gastric food retention. This study aimed to evaluate the incidence of gastric food retention after distal gastrectomy with gastrojejunostomy in gastric cancer patients and identify the risk factors for its development. @*Materials and Methods@#We retrospectively enrolled 245 patients who underwent distal gastrectomy with gastrojejunostomy for gastric cancer at Boramae Medical Center between March 2017 and December 2019. We analyzed the presence of gastric food residue via computed tomography (CT) scans at 3 and 12 months postoperatively and analyzed the risk factors that may influence the development of gastric food retention. @*Results@#CT scans were performed on 235 patients at 3 months and on 217 patients at 12 months postoperatively. In the group that received closure of Petersen's space, the incidence of gastric food retention was significantly low as per the 3- and 12-month postoperative follow-up CT scans (P=0.028 and 0.003, respectively). In addition, hypertension was related to gastric food retention as per the 12-month postoperative follow-up CT scans (P=0.011). No other factors were related to the development of gastric food retention. In the multivariate analysis, non-closure of Petersen's space (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.20–5.38; P=0.010) was the only significant risk factor for gastric food retention at 3 months postoperatively, while non-closure of Petersen's space (HR, 2.81; 95% CI, 1.40-5.64;P=0.004) and hypertension (HR, 2.30; 95% CI, 1.14–4.63; P=0.020) were both significant risk factors for gastric food retention at 12 months postoperatively. @*Conclusions@#Closure of Petersen's space has an effect on decrease the incidence of gastric food retention after distal gastrectomy with gastrojejunostomy in gastric cancer patients.

Renal Safety of Repeated Intravascular Administrations of Iodinated or Gadolinium-Based Contrast Media within a Short Interval

Objective@#We aimed to investigate whether repeated intravascular administration of iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCAs) within a short interval was associated with an increased risk of post-contrast acute kidney injury (PC-AKI). @*Materials and Methods@#This retrospective study included 300 patients (mean age ± standard deviation, 68.5 ± 8.1 years; 131 male and 169 female) who had undergone at least one ICM-enhanced perfusion brain CT scan, had their baseline and follow-up serum creatinine levels available, and had not undergone additional contrast-enhanced examinations 72 hours before and after a time window of interest were included. The study population was divided into three groups: single-dose group and groups of patients who had received multiple contrast administrations in the time window of interest with the minimum contrast repeat interval either within 4 hours (0–4-hour group) or between 4 to 48 hours (4–48-hour group).Multivariable logistic regression analysis was conducted to evaluate the association between AKI and repeated ICM administrations. A similar supplementary analysis was performed including both ICM and GBCA. @*Results@#When ICM was only considered ignoring GBCA, among 300 patients, 207 patients received a single dose of ICM, 58 had repeated doses within 4 hours (0–4-hour group), and 35 patients had repeated doses between 4 to 48 hours (4–48-hour group). Most patients (> 95%) had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2 . AKI occurred in 7.2%, 13.8%, and 8.6% of patients in the single-dose, 0–4-hour, and 4–48-hour groups, respectively. In the 0–4-hour and 4–48-hour groups, additional exposure to ICM was not associated with AKI after adjusting for comorbidities and nephrotoxic drugs (all p values > 0.05). @*Conclusion@#Repeated intravascular administrations of ICM within a short interval did not increase the risk of AKI in our study patients suspected of acute stroke with a baseline eGFR of ≥ 30 mL/min/1.73 m2 .

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study

Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

Renal Safety of Repeated Intravascular Administrations of Iodinated or Gadolinium-Based Contrast Media within a Short Interval

Objective@#We aimed to investigate whether repeated intravascular administration of iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCAs) within a short interval was associated with an increased risk of post-contrast acute kidney injury (PC-AKI). @*Materials and Methods@#This retrospective study included 300 patients (mean age ± standard deviation, 68.5 ± 8.1 years; 131 male and 169 female) who had undergone at least one ICM-enhanced perfusion brain CT scan, had their baseline and follow-up serum creatinine levels available, and had not undergone additional contrast-enhanced examinations 72 hours before and after a time window of interest were included. The study population was divided into three groups: single-dose group and groups of patients who had received multiple contrast administrations in the time window of interest with the minimum contrast repeat interval either within 4 hours (0–4-hour group) or between 4 to 48 hours (4–48-hour group).Multivariable logistic regression analysis was conducted to evaluate the association between AKI and repeated ICM administrations. A similar supplementary analysis was performed including both ICM and GBCA. @*Results@#When ICM was only considered ignoring GBCA, among 300 patients, 207 patients received a single dose of ICM, 58 had repeated doses within 4 hours (0–4-hour group), and 35 patients had repeated doses between 4 to 48 hours (4–48-hour group). Most patients (> 95%) had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2 . AKI occurred in 7.2%, 13.8%, and 8.6% of patients in the single-dose, 0–4-hour, and 4–48-hour groups, respectively. In the 0–4-hour and 4–48-hour groups, additional exposure to ICM was not associated with AKI after adjusting for comorbidities and nephrotoxic drugs (all p values > 0.05). @*Conclusion@#Repeated intravascular administrations of ICM within a short interval did not increase the risk of AKI in our study patients suspected of acute stroke with a baseline eGFR of ≥ 30 mL/min/1.73 m2 .

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study

Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

The Importance of Early Recognition, Timely Management, and the Role of Healthcare Providers in Multisystem Inflammatory Syndrome in Children

In April 2020, a pediatric report of an unusual inflammatory illness associated with coronavirus disease 2019 (COVID-19) led to similar cases in Europe and North America, which was referred to as multisystem inflammatory syndrome in children (MIS-C). Herein, we describe the case of a 12-year-old boy who had a history of polymerase chain reactionconfirmed COVID-19 and developed MIS-C approximately three weeks after an initial diagnosis of COVID-19. High fever with abdominal pain mimicking appendicitis was the initial manifestation of MIS-C, which could have been easily missed if the patient's history of COVID-19 was ignored. Intravenous immunoglobulin was administered twice, 24 hours apart, five days after the onset of MIS-C, and the patient fully recovered without any obvious sequelae. Early recognition by disease awareness and prompt management are the keys to saving the lives of children affected by MIS-C.

Are the elderly patient’s changes in the health‑related quality of life one year after gastrectomy for stomach cancer different from those in young patients?

Purpose@#Gastrectomy for elderly patients can significantly deteriorate the health-related quality of life (HRQoL). There was no report comparing HRQoL of elderly patients with young patients after gastrectomy for gastric cancer. This study assessed the differences in the changes of HRQoL at one year after gastrectomy according to age. @*Methods@#From May 2014 to Feb 2016, we prospectively enrolled patients undergoing gastrectomy for gastric cancer. They completed the European Organization for Research and Treatment of Cancer and gastric questionnaires preoperatively and at postoperative 1, 3, 6, 9, and 12 months. @*Results@#We included 57 elderly patients (≥70 years old) and 74 younger patients. The elderly had similar demographic, surgical, and pathological characteristics with young patients except that elderly had more comorbidity, laparoscopic gastrectomies, and lesser postoperative chemotherapy. One month after gastrectomy, the score of global health status/ quality of life, physical, role, and social functioning were significantly impaired in elderly patients. Among them, physical and role functioning were more impaired than those of young patients. The scores of physical functioning, role functioning, cognitive functioning, and social functioning were not fully recovered till 1 year after surgery. There was a significant age group difference in the changes in physical function over the 1-year follow-up. @*Conclusion@#Elderly patients’ global health status/quality of life and social functioning significantly decreased at postoperative 1 month and recovered by 6 months after gastrectomy. There was a significant age-specific difference in physical functioning throughout the 1-year follow-up. Surgeons need to pay more attention to recovery of the elderly patients’ HRQoL after gastrectomy.

Comparing the surgical outcomes of dual-port laparoscopic distal gastrectomy and three-port laparoscopic distal gastrectomy for gastric cancer

Purpose@#Many studies have demonstrated that single-incision or reduced-port laparoscopic distal gastrectomy is a feasible method compared to conventional laparoscopic distal gastrectomy. Using rigid-type laparoscope and right-side approach, we could perform dual-port laparoscopic distal gastrectomy (DPLDG) for gastric cancer. This study aimed to compare the surgical outcomes of DPLDG to those of 3-port laparoscopic distal gastrectomy (TPLDG). @*Methods@#From March 2017 to December 2019, this retrospective study included 218 patients with gastric cancer who underwent DPLDG (106 patients) or TPLDG (112 patients) at SMG-SNU Boramae Medical Center. Surgical outcomes were compared between 2 operation methods. @*Results@#Operation time was similar between DPLDG and TPLDG (158.9 ± 33.4 minutes vs. 154.0 ± 31.1 min, P = 0.787). The number of retrieved lymph nodes was similar between the 2 groups (35.3 ± 14.6 vs. 37.0 ± 13.5, P = 0.415). The complication rate in DPLDG and TPLDG groups was 10.4% and 8.9%, respectively (P = 0.894). The time to first flatus, time to first diet, and postoperative hospital stay were similar between the 2 groups. There were no reoperation or mortality cases. The cost of trocars was 359.9 US dollars (USD) in DPLDG and 291–391.4 USD in TPLDG. @*Conclusion@#The surgical outcomes of DPLDG and TPLDG did not differ. Regarding fewer incisions, DPLDG can be an alternative option for TPLDG.