Search

Background: The objective of this study was to determine the incidence of tuberculosis (TB) among workers at medical institutions based on interferon-gamma release assay (IGRA) and compare it with that of workers at educational institutions and the general population. Methods: From March 2017 to December 2020, we used a cohort of workers from medical and educational institutions in Korea, who underwent IGRA as part of a national screening program for latent tuberculosis infection (LTBI). After connecting to the National Health Insurance Service (NHIS) database to detect for any actual cases of active TB, we estimated standardized incidence ratio (SIR) and the expected number of cases to compare the incidence of TB with that of the general population. Results: Significant disparities in TB incidence were revealed among workers in medical and educational institutions, based on IGRA results, age, and occupation. Individuals positive for IGRA in medical institutions displayed substantially higher SIR for TB, 7.19 (6.15–8.41), compared to counterparts in educational institutions, 3.69 (3.02–4.51). Comparing by age group, we see that the SIRs are higher in younger age groups compared to older ones, with 37.30 (28.11–49.50) and 11.89 (7.28–19.41) for IGRA-positive medical and education workers under 30 years of age, respectively. In the results by occupation within the medical institutions, nurses had the highest SIR at 14.17 (11.14–18.04). Conclusions: Healthcare workers in medical institutions are more likely to develop actual TB after a positive result of LTBI screening in Korea. Intensive management and surveillance programs should be reinforced.

Abstract Optimal strategy for volume control and the clinical implication of achieved volume control are unknown in patients with sepsis-associated acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). This randomized controlled trial aimed to compare the survival according to conventional or bioelectrical impedance analysis (BIA)-guided volume control strategy in patients with sepsis-associated AKI receiving CRRT. We also compared patient survival according to achieved volume accumulation rate ([cumulative fluid balance during 3 days × 100]/fluid overload measured by BIA at enrollment) as a post-hoc analysis. We randomly assigned patients to conventional volume control strategy (n = 39) or to BIA-guided volume control strategy (n = 34). There were no differences in 28-day mortality (HR, 1.19; 95% CI, 0.63–2.23) or 90-day mortality (HR, 0.99; 95% CI 0.57–1.75) between conventional and BIA-guided volume control group. In the secondary analysis, achieved volume accumulation rate was significantly associated with patient survival. Compared with the achieved volume accumulation rate of ≤ − 50%, the HRs (95% CIs) for the risk of 90-day mortality were 1.21 (0.29–5.01), 0.55 (0.12–2.48), and 7.18 (1.58–32.51) in that of − 50–0%, 1–50%, and > 50%, respectively. Hence, BIA-guided volume control in patients with sepsis-associated AKI receiving CRRT did not improve patient outcomes. In the secondary analysis, achieved volume accumulation rate was associated with patient survival.

Background Coronary artery calcification (CAC) is highly prevalent in patients with chronic kidney disease (CKD) and is associated with major adverse cardiovascular events and metabolic disturbances. The triglyceride-glucose index (TyGI), a novel surrogate marker of metabolic syndrome and insulin resistance, is associated with CAC in the general population and in patients with diabetes. This study investigated the association between the TyGI and CAC progression in patients with CKD, which is unknown. Methods A total of 1,154 patients with CKD (grades 1–5; age, 52.8 ± 11.9 years; male, 688 [59.6%]) were enrolled from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The TyGI was calculated as follows: ln (fasting triglycerides × fasting glucose/2). Patients were classified into tertiles (low, intermediate, high) based on the TyGI. The primary outcome was annualized percentage change in CAC score [(percent change in CAC score + 1)12/follow-up months – 1] of ≥15%, defined as CAC progression. Results During the 4-year follow-up, the percentage of patients with CAC progression increased across TyGI groups (28.6%, 37.5%, and 46.2% in low, intermediate, and high groups, respectively; p < 0.001). A high TyGI was associated with an increased risk of CAC progression (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.14–3.88; p = 0.02) compared to the low group. Moreover, a 1-point increase in the TyGI was related to increased risk of CAC progression (OR, 1.55; 95% CI, 1.06–1.76; p = 0.02) after adjustment. Conclusion A high TyGI may be a useful predictor of CAC progression in CKD.

IntroductionABO-incompatible (ABOi) kidney transplantation (KT) has become an important option to overcome organ shortage. Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABOi KT. However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR.MethodsEculizumab treatment was used an adjunctive therapy to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Molecular phenotypes of allograft biopsies and cellular phenotypes of peripheral blood mononuclear cells of eculizumab group were compared with those of control groups using the Banff Human Organ Transplant gene panel and flow-cytometric analysis, respectively.ResultsThe initial titers of anti-ABO antibodies in the two patients were 1:512 and >1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from KT day to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infection, despite early episodes of probable AMR or borderline T cell-mediated rejection. Molecular phenotype analysis revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells.ConclusionsShort-term eculizumab therapy is promising for rescuing ABOi KT recipients with high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy.

Background Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. Methods Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19–related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. Results Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. Conclusion This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19’s impact on GN.

Background Fluid overload is an independent risk factor of mortality in patients with acute kidney injury (AKI) receiving continuous kidney replacement therapy (CKRT). However, the association between fluid status, as assessed by bioelectrical impedance analysis (BIA) or lung ultrasound, and survival in patients with AKI requiring CKRT has not been established. Methods We analyzed 36 participants with sepsis-associated AKI who received CKRT at a tertiary hospital. The main exposures were volume surrogates: 1) overhydration normalized by extracellular water (OH/ECW, L/L) assessed by BIA, 2) the number of B-lines measured by lung ultrasound, and 3) weight change ([body weight at CKRT initiation – body weight at admission] × 100/body weight at admission). The primary outcome was the 28-day mortality. Results Seventeen participants (47.2%) died within 28 days. There were no significant correlations between OH/ECW and weight change (R2 = 0.040, p = 0.24), number of B-lines and OH/ECW (R2 = 0.056, p = 0.16), or weight change and number of B-lines (R2 = 0.014, p = 0.49). Kaplan-Meier analyses revealed that patients in the highest tertile of OH/ECW showed a significantly lower cumulative 28-day survival probability than the others (the lowest + middle tertiles). The survival probability of participants in the highest tertile of the number of B-lines or weight change did not differ from that of their counterparts. In a multivariate Cox proportional hazard model, the hazard ratio for the highest tertile of OH/ECW was 3.83 (95% confidence interval, 1.04–14.03). Conclusion Volume overload assessed using BIA (OH/ECW) was associated with the 28-day survival rate in patients with sepsis-associated AKI who received CKRT.

Post-tuberculosis lung disease (PTLD) is emerging as a significant area of global interest. As the number of patients surviving tuberculosis (TB) increases, the subsequent long-term repercussions have drawn increased attention due to their profound clinical and socioeconomic impacts. A primary obstacle to its comprehensive study has been its marked heterogeneity. The disease presents a spectrum of clinical manifestations which encompass tracheobronchial stenosis, bronchiectasis, granulomas with fibrosis, cavitation with associated aspergillosis, chronic pleural diseases, and small airway diseases—all persistent consequences of PTLD. The spectrum of symptoms a patient may experience varies based on the severity of the initial infection and the efficacy of the treatment received. As a result, the long-term management of PTLD necessitates a detailed and specific approach, addressing each manifestation individually—a tailored strategy. In the immediate aftermath (0–12 months after anti-TB chemotherapy), there should be an emphasis on monitoring for relapse, tracheobronchial stenosis, and smoking cessation. Subsequent management should focus on addressing hemoptysis, managing infection including aspergillosis, and TB-associated chronic obstructive pulmonary disease or restrictive lung function. There remains a vast expanse of knowledge to be discovered in PTLD. This review emphasizes the pressing need for comprehensive, consolidated guidelines for management of patients with PTLD.

BackgroundTimely pulmonary tuberculosis (PTB) diagnosis is a global health priority for interrupting transmission and optimizing treatment outcomes. The traditional dichotomous time-divided approach for addressing time delays in diagnosis has limited clinical application because the time delay significantly varies depending on each community in question. ObjectiveWe aimed to reevaluate the diagnosis time delay based on the PTB disease spectrum using a novel scoring system that was applied at the national level in the Republic of Korea. MethodsThe Pulmonary Tuberculosis Spectrum Score (PTBSS) was developed based on previously published proposals related to the disease spectrum, and its validity was assessed by examining both all-cause and PTB-related mortality. In our analysis, we integrated the PTBSS into the Korea Tuberculosis Cohort Registry. We evaluated various time delays, including patient, health care, and overall delays, and their system-associated variables in line with each PTBSS. Furthermore, we reclassified the scores into distinct categories of mild (PTBSS=0-1), moderate (PBTBSS=2-3), and severe (PBTBSS=4-6) using a multivariate regression approach. ResultsAmong the 14,031 Korean patients with active PTB whose data were analyzed from 2018 to 2020, 37% (n=5191), 38% (n=5328), and 25% (n=3512) were classified as having a mild, moderate, and severe disease status, respectively, according to the PTBSS. This classification can therefore reflect the disease spectrum of PTB by considering the correlation of the score with mortality. The time delay patterns differed according to the PTBSS. In health care delays according to the PTBSS, greater PTB disease progression was associated with a shorter diagnosis period, since the condition is microbiologically easy to diagnose. However, with respect to patient delays, the change in elapsed time showed a U-shaped pattern as PTB progressed. This means that a remarkable patient delay in the real-world setting might occur at both apical ends of the spectrum (ie, in both mild and severe cases of PTB). Independent risk factors for a severe PTB pattern were age (adjusted odds ratio 1.014) and male sex (adjusted odds ratio 1.422), whereas no significant risk factor was found for mild PTB. ConclusionsTimely PTB diagnosis should be accomplished. This can be improved with use of the PTBSS, a simple and intuitive scoring system, which can be more helpful in clinical and public health applications compared to the traditional dichotomous time-only approach.

Abstract Background Cold ischemia‐reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)‐2/anti‐IL‐2 antibody complex (IL‐2C) can ameliorate cold IRI. Methods We developed a cold IRI mouse model using kidney transplantation and analyzed the IL‐2C impact on cold IRI in acute, subacute and chronic phases. Results Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL‐2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro‐inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL‐2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL‐2C inhibited chronic fibrosis. IL‐2C decreased reactive oxygen species‐mediated injury and improved antioxidant function. When IL‐2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL‐2C eliminated the positive effects of IL‐2C on IRI. Conclusion Tregs protect kidneys from cold IRI and IL‐2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL‐2C in treating cold IRI. Key Points Interleukin (IL)‐2/anti‐IL‐2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia‐reperfusion injury (IRI) by increasing the renal Tregs. IL‐2/anti‐IL‐2 antibody complex decreased reactive oxygen species‐mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL‐2/anti‐IL‐2 antibody complex in kidney transplantation‐associated cold IR.

Background The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Methods We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease. Results During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with

Abstract De novo donor-specific antibody (dnDSA) is associated with a higher risk of kidney graft failure. However, it is unknown whether preemptive treatment of subclinical dnDSA is beneficial. Here, we assessed the efficacy of high-dose intravenous immunoglobulin (IVIG) and rituximab combination therapy for subclinical dnDSA. An open-label randomized controlled clinical trial was conducted at two Korean institutions. Adult (aged ≥ 19 years) kidney transplant patients with subclinical class II dnDSA (mean fluorescence intensity ≥ 1000) were enrolled. Eligible participants were randomly assigned to receive rituximab or rituximab with IVIG at a 1:1 ratio. The primary endpoint was the change in dnDSA titer at 3 and 12 months after treatment. A total of 46 patients (24 for rituximab and 22 for rituximab with IVIG) were included in the analysis. The mean baseline estimated glomerular filtration rate was 66.7 ± 16.3 mL/min/1.73 m2. The titer decline of immune-dominant dnDSA at 12 months in both the preemptive groups was significant. However, there was no difference between the two groups at 12 months. Either kidney allograft function or proteinuria did not differ between the two groups. No antibody-mediated rejection occurred in either group. Preemptive treatment with high-dose IVIG combined with rituximab did not show a better dnDSA reduction compared with rituximab alone. Trial registration : IVIG/Rituximab versus Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies (ClinicalTrials.gov Identifier: NCT04033276, first trial registration (26/07/2019).

Introduction: High sodium intake is associated with increased proteinuria. Herein, we investigated whether proteinuria could modify the association between urinary sodium excretion and adverse kidney outcomes in patients with chronic kidney disease (CKD). Methods: In this prospective observational cohort study, we included 967 participants with CKD stages G1 to G5 between 2011 and 2016, who measured 24-hour urinary sodium and protein excretion at baseline. The main predictors were urinary sodium and protein excretion levels. The primary outcome was CKD progression, which was defined as a ≥50% decline in the estimated glomerular filtration rate (eGFR) or the onset of kidney replacement therapy. Results: During a median follow-up period of 4.1 years, the primary outcome events occurred in 287 participants (29.7%). There was a significant interaction between proteinuria and sodium excretion for the primary outcome (P = 0.006). In patients with proteinuria of

ObjectiveThe clinical manifestations of tuberculosis (TB) range from asymptomatic to disseminated depending on the microbiological and immunological status, making the diagnosis challenging. To improve our understanding of the disease progression mechanism, we aimed to identify the characteristics of subclinical TB and important predictors of symptom development.MethodsFrom July 2018 to June 2019, we systemically collected data from the National Surveillance System of South Korea on patients with pulmonary TB, and compared the characteristics of subclinical and active symptomatic TB patients.ResultsA total of 4,636 patients with pulmonary TB were included, and the prevalence of subclinical TB was 37.1% (1,720/4,636). In subclinical TB patients, the positivity rates of acid-fast bacilli (AFB) smear and culture were 16.2 and 50.2%, respectively. Subclinical TB patients were younger (55.6 ± 19.2 vs. 60.7 ± 19.5, P < 0.001), had a higher body mass index (21.7 ± 3.1 vs. 21.0 ± 3.5, P < 0.001), less under Medicaid support, and had lower rates of chronic lung disease, AFB smear and culture positivity, and bilateral disease. Regarding the characteristic differences of individual TB-related symptoms, age was positively associated with dyspnoea and general weakness but negatively associated with chest pain, haemoptysis, and weight loss. Male patients were more prone to weight loss. Chronic lung disease was related to symptoms including cough/phlegm, dyspnoea, and haemoptysis, while autoimmune diseases were associated with fever and weight loss.ConclusionsThe development of TB-related symptoms was associated with microbiological burden and clinical characteristics including underlying comorbidities, which should be evaluated carefully.

Abstract Disparities exist between sexes regarding tuberculosis (TB) incidence, as well as disease severity and outcome. Using a nationwide TB registry database, we explored the impact of sex and age on extrapulmonary TB (EPTB) among all enrolled patients by (1) calculating the female proportion for every age category according to TB-affected locations, (2) calculating the proportions of EPTB stratified by sex according to age, (3) conducting multivariable analysis to examine the impact of sex and age on EPTB likelihood, and (4) assessing the odds of EPTB for female compared to male as reference in every age category. Further, we explored the impact of sex and age on disease severity among pulmonary TB (PTB) patients. Of all the TB patients, 40.1% were female, with a male-to-female ratio of 1.49. The proportion of females was lowest in their fifties, resembling a U-shape. The male-to-female ratios in PTB and EPTB were 1.67 and 1.03, respectively. Compared to men, women were significantly associated with EPTB in their forties, fifties, and sixties. Female patients with PTB had significantly lower odds of having cavitation and positive smear test results in their fifties. Significant differences were found concerning TB location and severity between sexes, especially during reproductive age.

Abstract Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00–2.77) and 1.20 (0.60–2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT.

Background Alzheimer disease (AD) and depressive disorder (DD) are prevalent among elderly end-stage kidney disease (ESKD) patients. However, whether preexisting mental health disorders increase the risk of ESKD is not well understood. The risk of incident ESKD in patients with or without underlying AD or DD was evaluated in a nationwide cohort of elderly people in Republic of Korea. Methods This study used data from the National Health Insurance Service-Senior cohort in Republic of Korea. Among the 558,147 total subjects, 49,634 and 54,231 were diagnosed with AD (AD group) or DD (DD group), respectively, during the follow-up period. Propensity score matching was conducted to create non-AD and non-DD groups of subjects. AD and DD diagnoses were analyzed as time-varying exposures, and the study outcome was development of ESKD. Results The incidence rates of ESKD were 0.36 and 1.17 per 1,000 person-years in the non-AD and AD groups, respectively. After adjustment for clinical variables and competing risks of death, the risk of incident ESKD was higher in the AD group than in the non-AD group (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.34–2.08). The incidence rates of ESKD in the non-DD and DD groups were 0.36 and 0.91 per 1,000 person-years, respectively. The risk of ESKD development was also higher in the DD group than the non-DD group (HR, 1.44; 95% CI, 1.19–1.76). Conclusion The risk of ESKD development was higher in subjects diagnosed with AD or DD, suggesting that central nervous system diseases can adversely affect kidney function in elderly people.

Abstract Background Tuberculosis (TB) is a highly heterogeneous disease that can affect any organ. Extrapulmonary TB (EPTB) is more difficult to diagnose due to various clinical presentations. Depending on the characteristics of the patient, the involved site of TB may vary. However, data on clinical characteristics of EPTB are inconsistent and insufficient. This study aimed to identify the characteristics of patients with pulmonary TB (PTB) and EPTB and describe characteristic differences for each involved site. Methods We systemically collected data of TB patients included in the national surveillance system in South Korea from July 2018 to June 2019 and compared the characteristics of patients with EPTB with that of PTB. Results A total of 7674 patients with a mean age of 60.9 years were included. Among them, 6038 (78.7%) patients were diagnosed with PTB and 1636 (21.3%) with EPTB. In PTB group, the mean age (61.7 ± 18.7 vs. 57.8 ± 19.9) and proportion of male sex (63.3% vs. 50.1%) were higher, but the body mass index was lower (21.2 ± 3.4 vs. 22.7 ± 3.5) than that of the EPTB group. Prevalence of diabetes (20.5% vs. 16.9%) and chronic lung disease (5.1% vs. 2.9%) were higher in PTB group, meanwhile, those of chronic kidney disease (CKD) (2.7% vs. 5.4%) and long-term steroid use (0.4% vs. 1.0%) were higher in EPTB group. Abdominal TB was more prevalent in patients with chronic liver disease (odds ratio [OR]: 2.69, 95% CI: 1.52–4.74), and urogenital TB was more prevalent in patients with CKD (OR: 2.75, 95% CI: 1.08–6.99). Conclusions We found that underlying comorbidities were closely associated with the location of TB development, and therefore, the possibility of EPTB should be carefully evaluated while monitoring for underlying disease in TB-endemic areas.

IntroductionIn South Korea, public-private mix (PPM) has been a key strategy in national tuberculosis (TB) control program. This study aimed to identify rate of loss to follow-up (LTFU) among TB patients in nationwide PPM institutions and their risk factors.MethodsA nationwide prospective observational study including drug susceptible TB patients diagnosed from the 1st day to the 10th day of every month between July 2018 and December 2020 in PPM institutions was designed. Multivariable survival models in which death and failure were designated as events with competing risk were used to investigate risk factors for LTFU.ResultsA total of 14,942 patients were included. Of them, 356 (2.4%) had an LTFU. Risk factors for LTFU were: underweight patients (adjusted hazard ratio (aHR): 1.47, 95% CI: 1.12–1.92), patients living alone (aHR: 1.43, 95% CI: 1.16–1.76), heavy drinkers (aHR: 1.67, 95% CI: 1.16–2.39), those with malignancy (aHR: 1.49, 95% CI: 1.07–2.05), foreigners (aHR: 5.96, 95% CI: 4.51–7.89), and those with previous TB history reported as an unfavorable outcome (aHR: 4.43, 95% CI: 2.77–7.08). Effect of age on LTFU was not significant. Brief interruption of anti-TB treatment (less than two months) in current session was associated with subsequent LTFU [adjusted odds ratio: 13.09 (10.29–16.66)].ConclusionIdentifying vulnerability of patients such as living alone, being heavy alcoholics, being foreigners or having previous TB history reported as an unfavorable outcome is required. Thorough case management for these vulnerable groups could be feasible with collaboration between public and private sectors.

BackgroundPoor nutrition increases disease severity and mortality in patients with tuberculosis (TB). There are gaps in our understanding of the effects of being underweight or overweight on TB in relation to sex.MethodsWe generated a nationwide TB registry database and assessed the effects of body mass index (BMI) on mortality in patients with pulmonary TB. The cause of death was further classified as TB-related or non-TB-related deaths. First, logistic regression analysis was performed to assess the association between BMI (a continuous variable) and mortality, and subgroup analyses of the multivariable logistic regression model were performed separately in male and female patients. Second, we categorized BMI into three groups: underweight, normal weight, and overweight, and assessed the impact of being underweight or overweight on mortality with reference to normal weight.ResultsAmong 9,721 patients with pulmonary TB, the mean BMI was 21.3 ± 3.4; 1,927 (19.8%) were underweight, and 2,829 (29.1%) were overweight. In multivariable logistic regression analysis, mortality was significantly increased with the decrement of BMI (adjusted odds ratio [aOR] = 0.893, 95% confidence interval [CI] = 0.875–0.911). In subgroup analyses, underweight patients had significantly higher odds of mortality, especially TB-related deaths (aOR = 2.057, 95% CI = 1.546–2.735). The association with mortality and male patients was higher (aOR = 2.078, 95% CI = 1.717–2.514), compared with female patients (aOR = 1.724, 95% CI = 1.332–2.231). Being overweight had a significant protective effect against TB-related death only in females (aOR = 0.500, 95% CI = 0.268–0.934), whereas its effect on non-TB-related death was observed only in males (aOR = 0.739, 95% CI = 0.587–0.930).ConclusionBeing underweight was linked to high mortality, whereas being overweight had beneficial effects in patients with pulmonary TB.

ObjectiveTuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide. The first step in developing strategies to reduce TB mortality is to identify the direct causes of death in patients with TB and the risk factors for each cause.MethodsData on patients with TB systemically collected from the National Surveillance System of South Korea from January 2019 to December 2020 were included in this study. We analyzed the clinical characteristics associated with TB and non-TB-related deaths, including TB-related symptoms, comorbidities, and radiographic and microbiological findings.ResultsOf the total of 12,340 patients with TB, 61% were males with a mean age of 61.3 years. During the follow-up period, the overall mortality rate was 10.6%, with TB-related deaths accounting for 21.3% of all TB deaths. The median survival time in the TB-related death group was 22 days. TB-related death was associated with older age, lower body mass index (BMI), dyspnea, fever, general weakness, bilateral radiographic patterns, and acid-fast bacilli (AFB)-positive smears. Non-TB-related deaths were associated with older age, male sex, lower BMI, comorbidities of heart, liver, kidney, and central nervous system (CNS) diseases, CNS TB involvement, the presence of dyspnea, general weakness, and bilateral radiographic patterns.ConclusionPatients with high-risk TB must be identified through cause-specific mortality analysis, and the mortality rate must be reduced through intensive monitoring of patients with a high TB burden and comorbidities.

Background The International IgA Nephropathy Prediction Tool (International IgA Nephropathy Prediction Tool) has been recently developed to estimate the progression risk of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the clinical performance of this prediction tool in a large IgAN cohort in Korea. Methods The study cohort was comprised of 2,064 patients with biopsy-proven IgAN from four medical centers between March 2012 and September 2021. We calculated the predicted risk for each patient. The primary outcome was occurrence of a 50% decline in estimated glomerular filtration rate (eGFR) from the time of biopsy or end-stage kidney disease. The model performance was evaluated for discrimination, calibration, and reclassification. We also constructed and tested an additional model with a new coefficient for the Korean race. Results During a median follow-up period of 3.8 years (interquartile range, 1.8–6.6 years), 363 patients developed the primary outcome. The two prediction models exhibited good discrimination power, with a C-statistic of 0.81. The two models generally underestimated the risk of the primary outcome, with lesser underestimation for the model with race. The model with race showed better performance in reclassification compared to the model without race (net reclassification index, 0.13). The updated model with the Korean coefficient showed good agreement between predicted risk and observed outcome. Conclusion In Korean IgAN patients, International IgA Nephropathy Prediction Tool had good discrimination power but underestimated the risk of progression. The updated model with the Korean coefficient showed acceptable calibration and warrants external validation.

Abstract Background Muscle wasting is prevalent in cancer patients, and early recognition of this phenomenon is important for risk stratification. Recent studies have suggested that the creatinine–cystatin C ratio may correlate with muscle mass in several patient populations. The association between creatinine–cystatin C ratio and survival was assessed in cancer patients. Methods A total of 3060 patients who were evaluated for serum creatinine and cystatin C levels at the time of cancer diagnosis were included. The primary outcome was 6‐month mortality. The 1‐year mortality, and length of intensive care unit (ICU) and hospital stay were also evaluated. Results The mean age was 61.6 ± 13.5 years, and 1409 patients (46.0%) were female. The median creatinine and cystatin C levels were 0.9 (interquartile range [IQR], 0.6–1.3) mg/dL and 1.0 (IQR, 0.8–1.5) mg/L, respectively, with a creatinine–cystatin C ratio range of 0.12–12.54. In the Cox proportional hazards analysis, an increase in the creatinine–cystatin C ratio was associated with a significant decrease in the 6‐month mortality (per 1 creatinine–cystatin C ratio, hazard ratio [HR] 0.35; 95% confidence interval [CI], 0.28–0.44). When stratified into quartiles, the risk of 6‐month mortality was significantly lower in the highest quartile (HR 0.30; 95% CI, 0.24–0.37) than in the lowest quartile. Analysis of 1‐year mortality outcomes revealed similar findings. These associations were independent of confounding factors. The highest quartile was also associated with shorter lengths of ICU and hospital stay (both P

Objectives: This study was performed to develop a population pharmacokinetic model of pyrazinamide for Korean tuberculosis (TB) patients and to explore and identify the influence of demographic and clinical factors, especially geriatric diabetes mellitus (DM), on the pharmacokinetics (PK) of pyrazinamide (PZA).Methods: PZA concentrations at random post-dose points, demographic characteristics, and clinical information were collected in a multicenter prospective TB cohort study from 18 hospitals in Korea. Data obtained from 610 TB patients were divided into training and test datasets at a 4:1 ratio. A population PK model was developed using a nonlinear mixed-effects method.Results: A one-compartment model with allometric scaling for body size effect adequately described the PK of PZA. Geriatric patients with DM (age >70 years) were identified as a significant covariate, increasing the apparent clearance of PZA by 30% (geriatric patients with DM: 5.73 L/h; others: 4.50 L/h), thereby decreasing the area under the concentration–time curve from 0 to 24 h by a similar degree compared with other patients (geriatric patients with DM: 99.87 μg h/mL; others: 132.3 μg h/mL). Our model was externally evaluated using the test set and provided better predictive performance compared with the previously published model.Conclusion: The established population PK model sufficiently described the PK of PZA in Korean TB patients. Our model will be useful in therapeutic drug monitoring to provide dose optimization of PZA, particularly for geriatric patients with DM and TB.

Abstract In South Korea, public–private mix (PPM) was launched in 2011. This retrospective cohort study sought to determine the rate of loss to follow-up (LTFU) among drug-susceptible tuberculosis (DS-TB) patients in all nationwide PPM institutions, and the risk factors for LTFU. National notification data for DS-TB patients diagnosed between August 2011 and July 2014 in PPM institutions were analysed. Determination of LTFU included detection of instances where patients were transferred out, but when they did not attend at other TB centres in the following two months. Univariable and multivariable competing risk models were used to determine risk factors for LTFU. 73,046 patients with 78,485 records were enrolled. Nominally, 3426 (4.4%) of records were LTFU. However, after linking the multiple records in each patient, the percentage of LTFU was 12.3% (9004/73,046). Risk factors for LTFU were: being foreign-born (3.13 (95% CI 2.77–3.53)), prior LTFU (2.31 (2.06–2.59)) and greater distance between the patient’s home and the TB centre (4.27 (4.03–4.53)). ‘Transfer-out’ was a risk factor in patients managed by treatment centres close to home (1.65 (1.49–1.83)), but protective for those attending centres further (0.77 (0.66–0.89)) or far-away (0.52 (0.46–0.59)) from home. By considering the complete picture of a patient’s interactions with healthcare, we identified a much higher level of LTFU than previously documented. This has implications for how outcomes of treatment are reported and argues for a joined-up national approach for the management and surveillance of TB patients, in nations with similar healthcare systems.

Abstract Estimating the time delay and identifying associated factors is essential for effective tuberculosis control. We systemically analysed data obtained from the Korea Tuberculosis Cohort in 2019 by classifying delays as presentation and healthcare delays of pulmonary tuberculosis (PTB). Of 6593 patients with active PTB, presentation and healthcare delays were recorded in 4151 and 5571 patients, respectively. The median presentation delay was 16.0 (5.0–40.0) days. Multivariable logistic regression analysis showed that longer presentation delays were associated with neuropsychiatric disease [adjusted odds ratio (OR) 2.098; 95% confidence interval (CI) 1.639–2.687; p

Abstract Late Pneumocystis jirovecii pneumonia (PJP) is not rare in the era of universal prophylaxis after kidney transplantation. We aimed to determine the nationwide status of PJP prophylaxis in Korea and compare the incidence, risk factors, and outcomes of early and late PJP using data from the Korean Organ Transplantation Registry (KOTRY), a nationwide Korean transplant cohort. We conducted a retrospective analysis using data of 4,839 kidney transplant patients from KOTRY between 2014 and 2018, excluding patients who received multi-organ transplantation or were under 18 years old. Cox regression analysis was performed to determine risk factors for early and late PJP. A total of 50 patients developed PJP. The number of patients who developed PJP was same between onset before 6 months and onsets after 6 months. There were no differences in the rate, duration, or dose of PJP prophylaxis between early and late PJP. Desensitization, higher tacrolimus dose at discharge, and acute rejection were associated with early PJP. In late PJP, old age as well as acute rejection were significant risk factors. In conclusion late PJP is as common and risky as early PJP and requires individualized risk-based prophylaxis, such as prolonged prophylaxis for old patients with a history of rejection.

Abstract Statin use in end-stage kidney disease (ESKD) patients are not encouraged due to low cardioprotective effects. Although the risk of hepatocellular carcinoma (HCC), a frequently occurring cancer in East Asia, is elevated in ESKD patients, the relationship between statins and HCC is not known despite its possible chemopreventive effect. The relationship between statin use and HCC development in ESKD patients with chronic hepatitis was evaluated. In total, 6165 dialysis patients with chronic hepatitis B or C were selected from a national health insurance database. Patients prescribed with ≥ 28 cumulative defined daily doses of statins during the first 3 months after dialysis commencement were defined as statin users, while those not prescribed with statins were considered as non-users. Primary outcome was the first diagnosis of HCC. Sub-distribution hazard model with inverse probability of treatment weighting was used to estimate HCC risk considering death as competing risk. During a median follow-up of 2.8 years, HCC occurred in 114 (3.2%) statin non-users and 33 (1.2%) statin users. The HCC risk was 41% lower in statin users than in non-users (sub-distribution hazard ratio, 0.59; 95% confidence interval [CI], 0.42–0.81). The weighted incidence rate of HCC was lower in statin users than in statin non-users (incidence rate difference, − 3.7; 95% CI − 5.7 to − 1.7; P

Abstract Tuberculosis (TB) has a heterogeneous phenotype, which makes it challenging to diagnose. Our study aimed to identify TB phenotypes through cluster analysis and compare their initial symptomatic, microbiological and radiographic characteristics. We systemically collected data of notified TB patients notified in Korea and constructed a prospective, observational cohort database. Cluster analysis was performed using K-means clustering, and the variables to be included were determined by correlation network. A total of 4,370 subjects with pulmonary TB were enrolled in the study. Based on the correlation network, age and body mass index (BMI) were selected for the cluster analysis. Five clusters were identified and characterised as follows: (1) middle-aged overweight male dominance, (2) young-aged relatively female dominance without comorbidities, (3) middle-aged underweight male dominance, (4) overweight elderly with comorbidities and (5) underweight elderly with comorbidities. All clusters had distinct demographic and symptomatic characteristics. Initial microbiologic burdens and radiographic features also varied, including the presence of cavities and bilateral infiltration, which reflect TB-related severity. Cluster analysis of age and BMI identified five phenotypes of pulmonary TB with significant differences at initial clinical presentations. Further studies are necessary to validate our results and to assess their clinical implications.

Abstract As the burden of tuberculosis (TB) in South Korea decreases while that of malignancy increases with an aging society, the composition of etiology for pleural effusion is changing. The aim of this study was to investigate the diagnostic value of adenosine deaminase (ADA) for diagnosis of tuberculous pleural effusion (TPE) in this circumstance. Medical records of patients who underwent medical thoracoscopy from May 2015 to September 2020 in Incheon St. Mary Hospital, Korea were retrospectively reviewed. TPE was diagnosed if one of the following criteria was met: (1) granuloma in pleura, (2) positive TB polymerase chain reaction or culture in pleural fluid or tissue with non-specific pathologic findings in pleura, or (3) bacteriologically confirmed pulmonary TB with non-specific pathologic findings in pleura. A total of 292 patients, including 156 with malignant pleural effusion (MPE), 52 with TPE, and 84 with other benign effusion, were analyzed. Among 206 patients with lymphocyte dominant pleural effusion, the area under receiver characteristic curve of ADA for diagnosis of TPE was 0.971. The sensitivity and specificity of a current cutoff value of 40 IU/L were 1.00 and 0.61, respectively, whereas those of a raised cutoff value of 70 IU/L were 0.93 and 0.93, respectively. Among 54 patients with ADA levels of 40–70 IU/L, 30 (55.6%) patients were diagnosed as MPE, 21 (38.9%) as other benign effusion, and only 3 (5.6%) as TPE. Caution is needed in clinical diagnosis of TPE with current ADA cutoff value in countries with decreasing TB incidence, due to many false positive cases.

Abstract The strength of association between the body mass index (BMI) and blood pressure (BP) varies with population and time. Therefore, identifying the trends in BMI-BP association in adolescents can help predict the upcoming metabolic and cardiovascular disease burden. For this reason, from physical examination data collected from 2003 to 2017, a total of 5,133,246 Korean men aged 19 years were assessed for the annual trends and changes in the BMI-BP association. During the 15-year period, the mean BMI increased from 22.5 to 23.5 kg/m2, and the prevalence of obesity increased from 16.7 to 21.4%. Meanwhile, the mean systolic BP (SBP) decreased from 122.8 to 122.3 mmHg in the first year and gradually increased to 125.9 mmHg afterward. The diastolic BP (DBP) decreased from 71.5 to 70.0 mmHg in the first 4 years and then rose to 74.8 mmHg in the following years. The association analysis between BMI and SBP resulted in an annual increase in the correlation coefficient (SBP: 0.257–0.495, DBP: 0.164–0.413). The regression coefficient similarly increased between 2003 and 2015 but slightly decreased between 2015 and 2017 (SBP: 0.896–1.569, DBP: 0.405–0.861). The BMI-BP association increased over time (coefficient of the interaction term > 0, P

BackgroundThe Government of South Korea launched a national preemptive latent tuberculosis infection (LTBI) screening program in 2016, including more than 1. 6 million population in congregate settings. The objective of this study was to analyze LTBI prevalence and its risk factors in each setting. Additionally, the proportion of LTBI pool covered by the current national LTBI strategy was investigated.MethodsDatabase for results of interferon gamma release assay (IGRA), X-ray, and baseline demographic information was linked with National Health Information Database, national tuberculosis (TB) surveillance database, and national contact investigation database. Participants were categorized into three groups: Group A, workers of postpartum care centers, social welfare facilities and educational institutions; Group B, first year students in high school and out-of-school youths; and Group C, inmates of correctional facilities. Relative risks of LTBI by sex, age, place of living, income level, and comorbidities were calculated.ResultsA total of 444,394 participants in Group A, 272,224 participants in Group B, and 11,511 participants in Group C who participated in the national LTBI screening program between 2017 and 2018 were included, with LTBI prevalence of 20.7, 2.0, and 33.2%, respectively. Age was the single most important risk factor in Group A and Group C. Low-income level was another risk factor commonly identified in all groups. Among participants with positive IGRA results, 2.7, 4.4, and 3.3% in Groups A, B and C, respectively, had past TB exposure history since 2013. Current LTBI guideline targeting high or moderate TB risk disease covered 6.5, 0.6, and 1.1% of participants with positive IGRA results in Groups A, B and C, respectively.ConclusionOnly a small proportion of participants with positive IGRA results could be covered by the current LTBI strategy. Expansion of LTBI strategy by identifying further high-TB risk group in the general population is required.

In this study, we narrowly define the fidelity of additive manufacturing (AM) as the reliability of the morphology and mechanical properties of the fabricated structure. The structural design and fabrication of three-dimensional (3D) printed scaffolds produced using an extrusion technique for bone regeneration are actively studied with respect to their fidelity. However, fabricating an ideal design using an extrusion technique is difficult because of its intrinsic limitations in tissue engineering, such as those regarding resolution, manufacturing error, and printability. Among them, manufacturing errors and printability are partially or totally determined by the design complexity. Therefore, in extrusion-type AM, the design should be established considering the abovementioned limitations. In this study, the AM fidelity of a 3D Kagome scaffold was improved using design for additive manufacturing (DfAM). Consequently, the compressive stiffness was enhanced compared to that achieved in our previous study. Specifically, the compressive stiffness was improved to 95.2% of the computational analysis result, which is the maximum ideal value. In addition, the DfAM did not affect cell proliferation, showing that it can ensure the fabrication fidelity of 3D Kagome scaffolds without losing cell culturing characteristics.

Background/Aims The aim of the study was to investigate the current nationwide burden of nosocomial exposure to tuberculosis (TB) using national health insurance claims data. Methods All patients who had claims for drug susceptibility testing for TB from 2012 to 2016, which indicated culture-proven TB, were included. The first day of the infectious period was defined as 3 months before a doctor’s suspicion of TB in patients with respiratory symptoms and 1 month before in patients without symptoms. The last day of the infectious period was defined as one day before the prescription of anti-TB medications. Patients hospitalized during infectious periods were investigated and their hospitalization days were calculated. Records of medical procedures which increased the risk of nosocomial transmission by generating aerosols were also investigated. Results A total of 7,186 cases with 94,636 person-days of hospitalization with unrecognized active TB were found. Patients above 60 years of age accounted for 63.99% of the total number and 69.70% of the total duration of hospitalization. TB patients in the older age group showed a trend toward higher risks for hospitalization with unrecognized active TB. Patients in their 80s showed the highest risk (12.65%). Bronchoscopy (28.86%), nebulizer therapy (28.48%), and endotracheal intubation (13.02%) were common procedures performed in these patients during hospitalization. Conclusions The burden of nosocomial exposure to TB in South Korea is still substantial. Hospitalization with unrecognized active TB, especially among the elderly TB patients could be a serious public health issue in South Korea.

Background/Aims Despite controversy regarding the benefits of immunosuppressive therapy in immunoglobulin A nephropathy (IgAN), clinical outcomes may vary depending on the patient’s responsiveness to this therapy. This study evaluated long-term kidney outcomes according to the extent of proteinuria reduction after immunosuppression in IgAN patients. Methods Among 927 patients with biopsy-proven IgAN, 127 patients underwent immunosuppression. Time-averaged urine protein-creatinine ratio before and within 1 year after start of immunosuppression were calculated, and responsiveness to immunosuppression was assessed as the reduction of proteinuria between the two periods. Patients were classified into tertiles according to the extent of proteinuria reduction. We compared the slopes of estimated glomerular filtration rate (eGFR) decline using a linear mixed model, and estimated hazard ratios (HRs) for disease progression (defined as development of a ≥ 30% decline in eGFR or end-stage renal disease) using a Cox proportional hazard model. Results Median extent of proteinuria reduction was −2.1, −0.9, and −0.2 g/gCr in the first, second, and third tertiles, respectively. There were concomitant changes in the slopes of annual eGFR decline: −2.03, −2.44, and −4.62 mL/min/1.73 m2 among the first, second, and third tertiles, respectively. In multivariable Cox analysis, the HRs (95% confidence intervals) for disease progression were 0.30 (0.12 to 0.74) in the first tertile and 0.70 (0.34 to 1.45) in the second tertile compared with the thirdtertile. Conclusions This study showed that greater proteinuria reduction after immunosuppression was associated with a lower risk of disease progression in patients with IgAN, suggesting that responsiveness to immunosuppression may be an important determinant of kidney outcomes.

BackgroundIn 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework.Materials and methodsWe undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment.ResultsAmong the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20–34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people “not initiating treatment” (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95–3.86). Nine-month isoniazid monotherapy therapy was associated with “not completing treatment,” compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16–1.41).ConclusionAmong participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.

Abstract Dialysis adequacy is an important survival indicator in patients with chronic hemodialysis. However, there are inconveniences and disadvantages to measuring dialysis adequacy by blood samples. This study used machine learning models to predict dialysis adequacy in chronic hemodialysis patients using repeatedly measured data during hemodialysis. This study included 1333 hemodialysis sessions corresponding to the monthly examination dates of 61 patients. Patient demographics and clinical parameters were continuously measured from the hemodialysis machine; 240 measurements were collected from each hemodialysis session. Machine learning models (random forest and extreme gradient boosting [XGBoost]) and deep learning models (convolutional neural network and gated recurrent unit) were compared with multivariable linear regression models. The mean absolute percentage error (MAPE), root mean square error (RMSE), and Spearman’s rank correlation coefficient (Corr) for each model using fivefold cross-validation were calculated as performance measurements. The XGBoost model had the best performance among all methods (MAPE = 2.500; RMSE = 2.906; Corr = 0.873). The deep learning models with convolutional neural network (MAPE = 2.835; RMSE = 3.125; Corr = 0.833) and gated recurrent unit (MAPE = 2.974; RMSE = 3.230; Corr = 0.824) had similar performances. The linear regression models had the lowest performance (MAPE = 3.284; RMSE = 3.586; Corr = 0.770) compared with other models. Machine learning methods can accurately infer hemodialysis adequacy using continuously measured data from hemodialysis machines.

ObjectivePreviously developed Intradialytic hypotension (IDH) prediction models utilize clinical variables with potential privacy protection issues. We developed an IDH prediction model using minimal variables, without the risk of privacy infringement.MethodsUnidentifiable data from 63,640 hemodialysis sessions (26,746 of 79 patients for internal validation, 36,894 of 255 patients for external validation) from two Korean hospital hemodialysis databases were finally analyzed, using three IDH definitions: (1) systolic blood pressure (SBP) nadir

Background Whether visit‐to‐visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit‐to‐visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit‐to‐visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient‐years of follow‐up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit‐to‐visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80–3.36) and 2.23 (95% CI, 1.12–4.44), respectively, in a multivariable cause‐specific hazard model. In addition, the HR associated with each 5‐mm Hg increase in visit‐to‐visit SBP variability (SD) was 1.21 (95% CI, 1.01–1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03–4.35) and 2.28 (95% CI, 1.12–4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87–3.57) and 2.04 (95% CI, 1.03–4.03), respectively, with the variation independent of the mean. Conclusions Higher visit‐to‐visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Abstract Background To improve treatment outcomes for tuberculosis (TB), efforts to reduce treatment failure are necessary. The aim of our study was to describe the characteristics of subjects who had failed treatment of tuberculosis and identify the risk factors for treatment failure and poor compliance using national data. Methods A multicenter cross-sectional study was performed on tuberculosis subjects whose final outcome was reported as treatment failure during 2015–2017. The same number of subjects with treatment success during the same study period were randomly selected for comparison. Demographics, microbiological, radiographic, and clinical data were collected based on in-depth interviews by TB nurse specialists at all Public Private Mix (PPM) participating hospitals in South Korea. Results A total of 52 tuberculosis patients with treatment failure were enrolled. In a multivariable analysis, the presence of diabetes, previous history of tuberculosis, and cavity were identified as risk factors for treatment failure; and Medicaid support was a favorable factor for treatment success (area under the curve [AUC]: 0.79). Age, low body mass index (BMI), presence of diabetes, preexisting lung disease, positive sputum acid-fast bacilli (AFB) smear result, and the presence of multidrug-resistant tuberculosis (MDR-TB) were significantly associated with presence of cavities. Younger age, lower BMI and previous history of TB were associated with poor compliance during treatment (AUC: 0.76). Conclusion To reduce treatment failure, careful evaluation of the presence of diabetes, previous TB history, underlying lung disease, cavity, results of sputum AFB smears, and socioeconomic status are needed. To enhance treatment compliance, more attention should be paid to younger patients with lower BMIs during follow-up.

Background The national Public-Private Mix (PPM) tuberculosis (TB) control project provides for the comprehensive management of TB patients at private hospitals in South Korea. Surveillance and monitoring of TB under the PPM project are essential toward achieving TB elimination goals. Methods TB is a nationally notifiable disease in South Korea and is monitored using the surveillance system. The Korea Centers for Disease Control and Prevention quarterly generates monitoring indicators for TB management, used to evaluate activities of the PPM hospitals by the central steering committee of the national PPM TB control project. Based on the notification date, TB patients at PPM hospitals were enrolled in each quarter, forming a cohort, and followed up for at least 12 months to identify treatment outcomes. This report analyzed the dataset of cohorts the first quarter of 2016 through the fourth quarter of 2017. Results The coverage of sputum, smear, and culture tests among the pulmonary TB cases were 92.8% and 91.5%, respectively. The percentage of positive sputum smear and culture test results were 30.7% and 61.5%, respectively. The coverage of drug susceptibility tests among the culture-confirmed cases was 92.8%. The treatment success rate among the smear-positive drug-susceptible cases was 83.2%. The coverage of latent TB infection treatment among the childhood TB contacts was significantly higher than that among the adult contacts (85.6% vs. 56.0%, p=0.001). Conclusion This is the first official report to analyze monitoring indicators, describing the current status of the national PPM TB control project. To sustain its effect, strengthening the monitoring and evaluation systems is essential.

Abstract Background The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea. Methods Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15–34 years), middle (35–59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed. Results Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups. Conclusions The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.

In 2018, the World Health Organization recommended a 6-month four-drug regimen (rifampicin, ethambutol, pyrazinamide, and levofloxacin) for the treatment of isoniazid-monoresistant tuberculosis. However, the regimen had very low certainty. This cohort study assessed the impact of fluoroquinolone use and initial baseline regimen on treatment effectiveness in isoniazid-monoresistant tuberculosis. This multicenter retrospective cohort study included 318 patients with isoniazid-monoresistant tuberculosis notified between 2011 and 2018 in Korea. Baseline regimens were classified into two groups, namely 6-9-month rifampicin, ethambutol, and pyrazinamide (6-9REZ) and a combination regimen of 2-month rifampicin, ethambutol, pyrazinamide and 7-10-month rifampicin and ethambutol (2REZ/7-10RE). Multivariable logistic regression was performed to assess factors associated with positive treatment outcomes. Of 318 enrolled patients, 234 (73.6%) were treated with the 6-9REZ and 103 (32.4%) with additional fluoroquinolone. In a multivariable logistic regression model comparing the 6-9REZ and 2REZ/7-10RE groups, there was no difference in the odds of positive outcomes (adjusted odds ratio = 1.08, 95% confidence interval = 0.65-1.82). Addition use of fluoroquinolone was not associated with positive treatment outcomes in the whole cohort (adjusted odds ratio = 1.41, 95% confidence interval = 0.87-2.27); however, its additional use was beneficial in the 2REZ/7-10RE subgroup (adjusted odds ratio = 3.58, 95% confidence interval = 1.32-9.75). Both initial baseline regimens, 6-9REZ and 2REZ/7-10RE, were similarly effective. Shortening of the pyrazinamide administration duration with additional fluoroquinolone use could be a safe alternative for patients with potential hepatotoxicity related to pyrazinamide.

Objective: Dementia is prevalent among elderly patients undergoing hemodialysis. However, the association between dialysis adequacy and the risk of dementia is uncertain.Methods: A total of 10,567 patients aged >65 years undergoing maintenance hemodialysis who participated in a national hemodialysis quality assessment program were analyzed. The patients were classified into quartile groups based on single-pool Kt/V levels. The associations between single-pool Kt/V and the development of dementia, Alzheimer's disease (AD), and vascular dementia (VD) were examined.Results: The mean age of the patients was 72.9 years, and 43.4% were female. The mean baseline single-pool Kt/V level was 1.6 ± 0.3. During a median follow-up of 45.6 (45.6–69.9) months, there were 27.6, 23.9, and 2.8 events/1,000 person-years of overall dementia, AD, and VD, respectively. The incidences of overall dementia, AD, and VD were lowest in the highest single-pool Kt/V quartile group. Compared with the lowest single-pool Kt/V quartile, the risks of incident overall dementia and AD were significantly lower in the highest quartile [sub-distribution hazard ratio (sHR): 0.69, 95% confidence interval (CI): 0.58–0.82 for overall dementia; sHR: 0.69, 95% CI: 0.57–0.84 for AD]. Inverse relationships were found between the risks of developing overall dementia and AD, and single-pool Kt/V. However, no significant relationship was observed between single-pool Kt/V levels and VD development.Conclusions: Increased dialysis clearance was associated with a lower risk of developing dementia in elderly hemodialysis patients.

Soluble suppression of tumorigenesis-2 (sST2) is an emerging biomarker for sepsis as well as for heart failure. We investigated the prognostic utility of sST2 for predicting clinical outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. In a total of 52 hospitalized COVID-19 patients, sST2 levels were measured using the ichroma ST2 assay (Boditech Med Inc., Chuncheon-si, Gang-won-do, Republic of Korea). Clinical outcomes included intensive care unit (ICU) admission, ventilator use, extracorporeal membrane oxygenation (ECMO) use, and 30-day mortality. sST2 was analyzed according to clinical outcomes. sST2, sequential organ failure assessment (SOFA) score, critical disease, and 4C mortality score were compared using the receiver operating characteristic (ROC) curve and Kaplan–Meier methods for clinical outcomes. The sST2 level differed significantly according to ICU admission, ventilator use, ECMO use, and 30-day mortality (all p < 0.05). On ROC curve analysis, sST2 predicted ICU admission, ventilator use, ECMO use, and 30-day mortality comparable to SOFA score but significantly better than critical disease. sST2 predicted ICU admission, ventilator use, and ECMO use significantly better than the 4C mortality score. On Kaplan–Meier survival analysis, hazard ratios (95% confidence interval) were 8.4 (2.7–26.8) for sST2, 14.8 (3.0–71.7) for SOFA score, 1.8 (0.5–6.5) for critical disease, and 11.7 (3.4–40.1) for 4C mortality score. This study demonstrated that sST2 could be a useful biomarker to predict ICU admission, ventilator use, ECMO use, and 30-day mortality in hospitalized COVID-19 patients. sST2 may be implemented as a prognostic COVID-19 biomarker in clinical practice.

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.