Endoscopic Vacuum Therapy in Patients with Transmural Defects of the Upper Gastrointestinal Tract: A Systematic Review with Meta-Analysis

A transmural defect of the upper gastrointestinal (UGI) tract is a life-threatening condition associated with high morbidity and mortality. Recently, endoscopic vacuum therapy (EVT) was used for managing UGI defects and showed promising results. We conducted a systematic review and meta-analysis to synthesize evidence on the efficacy of EVT in patients with transmural defects of the UGI tract. We searched the PubMed, Cochrane Library, and Embase databases for publications on the effect of EVT on successful closure, mortality, complications, and post-EVT strictures. Methodological quality was assessed using the Newcastle-Ottawa quality assessment scale. This meta-analysis included 29 studies involving 498 participants. The pooled estimate rate of successful closure with EVT was 0.85 (95% confidence interval [CI]: 0.81-0.88). The pooled estimate rates for mortality, complications, and post-EVT strictures were 0.11, 0.10, and 0.14, respectively. According to the etiology of the transmural defect (perforation vs. leak and fistula), no significant difference was observed in successful closure (odds ratio [OR]: 1.45, 95% CI: 0.45-4.67, p = 0.53), mortality (OR: 0.77, 95% CI: 0.24-2.46, p = 0.66), complications (OR: 0.94, 95% CI: 0.17-5.15, p = 0.94), or post-EVT stricture rates (OR: 0.70, 95% CI: 0.12-4.24, p = 0.70). The successful closure rate was significantly higher with EVT than with self-expanding metal stent (SEMS) placement (OR: 3.14, 95% CI: 1.23-7.98, p = 0.02). EVT is an effective and safe treatment for leaks and fistulae, as well as for perforations in the UGI. Moreover, EVT seems to be a better treatment option than SEMS placement for UGI defects.ope

Permissive fluid volume in adult patients undergoing extracorporeal membrane oxygenation treatment

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a cardiorespiratory support technique for patients with circulatory or pulmonary failure. Frequently, large-volume fluid resuscitation is needed to ensure sufficient extracorporeal blood flow in patients initiating ECMO. However, excessive overhydration is known to increase mortality in critically ill patients. Therefore, in order to define a tolerant volume range in patients undergoing ECMO treatment, the association between cumulative fluid balance (CFB) and outcome was evaluated in patients undergoing ECMO. METHODS: This retrospective multicenter cohort study was conducted with 723 patients who underwent ECMO in three tertiary care hospitals between 2005 and 2016. CFB was calculated as total fluid input minus total fluid output during the first 3 days from ECMO initiation. The patients were divided into groups that initiated ECMO owing to cardiovascular disease (CVD)-related or non-cardiovascular disease (non-CVD)-related causes. The primary endpoint was mortality within 90 days after ECMO commencement. RESULTS: Totals of 406 and 317 patients were included in the CVD and non-CVD groups, respectively. In the CVD group, the mean age was 58.4 ± 17.7 years, and 68.2% were male. The mean age was 55.7 ± 15.7 years, and 65.3% were male in the non-CVD group. The median CFB values were 64.7 and 53.5 ml/kg in the CVD and non-CVD groups, respectively. Multivariable analysis using Cox proportional hazards models revealed a significantly increased risk of 90-day mortality in patients with higher CFB values in both the CVD and non-CVD groups. However, the risks were elevated only in the two CFB quartile groups with the largest CFB amounts. Cubic spline models showed that mortality risk began to increase significantly when CFB was 82.3 ml/kg in the CVD group. In patients with respiratory diseases, the mortality risk increase was significant for those with CFB levels above 189.6 ml/kg. CONCLUSIONS: Mortality risk did not increase until a certain level of fluid overload was reached in patients undergoing ECMO. Adequate fluid resuscitation is critical to improving outcomes in these patients.ope

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study

BACKGROUND: Guidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD. METHODS: A total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline. RESULTS: Patients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (β = - 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, β = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07-1.55; P = 0.007). CONCLUSIONS: High activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.ope

Dietary zinc intake and incident chronic kidney disease

Background & aims: Previous studies have shown that dietary zinc intake is closely related to cardiovascular complications and metabolic derangements. However, the effect of dietary zinc intake on renal function is not fully elucidated. Methods: Data from the Korean Genome and Epidemiology Study were used. Dietary zinc intake was assessed by a Food Frequency Questionnaire and dietary zinc density was calculated as absolute zinc intake amount per daily energy intake (mg/1000 kcal day). The participants were categorized into quartiles according to dietary zinc density. The primary end point was incident chronic kidney disease (CKD), defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. Results: A total of 7735 participants with normal renal function was included in the final analysis. The mean age was 52.0 ± 8.8 years, 47.5% were male, and mean eGFR was 92.1 ± 16.1 ml/min/1.73 m2. The mean daily zinc intake and zinc intake density were 8.6 ± 3.4 mg and 4.4 ± 0.9 mg/1000 kcal, respectively. During a median follow up of 11.5 (1.7-12.5) years and 70,617 person-years of observation, CKD developed in 1409 (18.2%) participants. Multivariable cox hazard analysis revealed that risk for CKD development was significantly higher in the quartile with a mean zinc intake density of 3.6 ± 0.2 mg/1000 kcal compared with the quartile with a mean zinc intake density of 5.6 ± 1.0 mg/1000 kcal (Hazard ratio; 1.36; 95% Confidence Interval 1.18-1.58; P < 0.001). This relationship remained significant even after adjustments for confounding factors. Conclusion: Low dietary zinc intake may increase the risk of CKD development in individuals with normal renal function.ope

Association of smoking with incident CKD risk in the general population: A community-based cohort study

Background: Chronic kidney disease (CKD) is a public health problem, and an unfavorable lifestyle has been suggested as a modifiable risk factor for CKD. Cigarette smoking is closely associated with cardiovascular disease and cancers; however, there is a lack of evidence to prove that smoking is harmful for kidney health. Therefore, we aimed to determine the relationship between cigarette smoking and CKD among healthy middle-aged adults. Methods: Using the database from the Korean Genome and Epidemiology Study, we analyzed 8,661 participants after excluding those with baseline estimated glomerular filtration rate (eGFR)<60 ml/min/1.72 m2 or proteinuria. Exposure of interest was smoking status: never-, former-, and current-smokers. Primary outcome was incident CKD defined as eGFR <60 ml/min/1.73 m2 or newly developed proteinuria. Results: The mean age of the subjects was 52 years, and 47.6% of them were males. There were 551 (6.4%) and 1,255 (14.5%) subjects with diabetes and hypertension, respectively. The mean eGFR was 93.0 ml/min/1.73 m2. Among the participants, 5,140 (59.3%), 1,336 (15.4%), and 2,185 (25.2%) were never-smokers, former-smokers, and current-smokers, respectively. During a median follow-up of 11.6 years, incident CKD developed in 1,941 (22.4%) subjects with a crude incidence rate of 25.1 (24.0-26.2) per 1,000 person-years. The multivariable Cox regression analysis after adjustment of confounding factors showed hazard ratios (95% confidence interval) of 1.13 (0.95-1.35) and 1.26 (1.07-1.48) for CKD development in the former- and current-smokers, compared with never-smokers. Conclusion: This study showed that smoking was associated with a higher risk of incident CKD among healthy middle-aged adults.ope

Machine Learning Improves the Prediction Rate of Non-Curative Resection of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer

Non-curative resection (NCR) of early gastric cancer (EGC) after endoscopic submucosal dissection (ESD) can increase the burden of additional treatment and medical expenses. We aimed to develop a machine-learning (ML)-based NCR prediction model for EGC prior to ESD. We obtained data from 4927 patients with EGC who underwent ESD between January 2006 and February 2020. Ten clinicopathological characteristics were selected using extreme gradient boosting (XGBoost) and were used to develop a ML-based model. Dataset was divided into the training and internal validation sets and verified using an external validation set. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were evaluated. The performance of each model was compared by using the Delong test. A total of 1100 (22.1%) patients were identified as being treated non-curatively with ESD. Seven ML-based NCR prediction models were developed. The performance of NCR prediction was highest in the XGBoost model (AUROC, 0.851; 95% confidence interval, 0.837-0.864). When we compared the prediction performance by the Delong test, XGBoost (p = 0.02) and support vector machine (p = 0.02) models showed a significantly higher performance among the NCR prediction models. We developed an ML model capable of accurately predicting the NCR of EGC before ESD. This ML model can provide useful information for decision-making regarding the appropriate treatment of EGC before ESD.ope

Colchicine use and the risk of CKD progression: a multicentre nested case-control study

Objectives: Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout. Methods: We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3-G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex. Results: Overall, 3085 patients with CKD progression were matched to 11 715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3. Conclusion: Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout.ope

Carbohydrate-Rich Diet Is Associated with Increased Risk of Incident Chronic Kidney Disease in Non-Diabetic Subjects

Despite the potential relationship with metabolic derangements, the association between dietary carbohydrate intake and renal function remains unknown. The present study investigated the impact of dietary carbohydrate intake on the development of incident chronic kidneydisease (CKD) in a large-scale prospective cohort with normal renal function. A total of 6746 and 1058 subjects without and with diabetes mellitus (DM) were analyzed, respectively. Carbohydrate intake was assessed by a 24-h dietary recall food frequency questionnaire. The primary endpoint was CKD development, defined as a composite of estimated glomerular filtration rate (eGFR) of ≤60 mL/min/1.73 m2 and the development of proteinuria. CKD newly developed in 20.1% and 36.0% of subjects during median follow-ups of 140 and 119 months in the non-DM and DM subjects, respectively. Categorization of non-DM subjects into dietary carbohydrate density quartiles revealed a significantly higher risk of CKD development in the third and fourth quartiles than in the first quartile (P = 0.037 for first vs. third; P = 0.001 for first vs. fourth). A significant risk elevation was also found with increased carbohydrate density when carbohydrate density was treated as a continuous variable (P = 0.008). However, there was no significant difference in the incident CKD risk among those with DM according to dietary carbohydrate density quartiles. Carbohydrate-rich diets may increase the risk of CKD development in non-DM subjects.ope

Increased Risk of Chronic Kidney Disease Associated With Weight Gain in Healthy Adults: Insight From Metabolic Profiles and Body Composition

Objective: Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD). Methods: For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories. Results: During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively (P = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06-1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06-1.87) and 2.2 (95% CI, 1.40-3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased. Conclusion: Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.ope

Framingham risk score and risk of incident chronic kidney disease: A community-based prospective cohort study

Background: Cardiovascular disease and chronic kidney disease share several common risk factors. The Framingham risk score is hypothesized to predict chronic kidney disease development. We determined if the Framingham risk scoring system can correctly predict incident chronic kidney disease in the general population. Methods: This study included 9,080 subjects who participated in the Korean Genome and Epidemiology Study between 2001 and 2014 and had normal renal function. The subjects were classified into low- ( 20%) risk groups based on baseline Framingham risk scores. The primary endpoint was de novo chronic kidney disease development (estimated glomerular filtration rate [eGFR], < 60 mL/min/1.73 m2). Results: During a mean follow-up duration of 8.9 ± 4.3 years, 312 (5.3%), 217 (10.8%), and 205 (16.9%) subjects developed chronic kidney disease in the low, intermediate, and high risk groups, respectively (P < 0.001). Multivariable analysis after adjustment for confounding factors showed the hazard ratios for the high- and intermediate risk groups were 2.674 (95% confidence interval [CI], 2.197-3.255) and 1.734 (95% CI, 1.447-2.078), respectively. This association was consistently observed irrespective of proteinuria, age, sex, obesity, or hypertension. The predictive power of this scoring system was lower than that of renal parameters, such as eGFR and proteinuria, but increased when both were included in the prediction model. Conclusion: The Framingham risk score predicted incident chronic kidney disease and enhanced risk stratification in conjunction with traditional renal parameters in the general population with normal renal function.ope