Gcap14 is a microtubule plus-end-tracking protein coordinating microtubule-actin crosstalk during neurodevelopment.

Regulation of microtubule dynamics is required to properly control various steps of neurodevelopment. In this study, we identified granule cell antiserum-positive 14 (Gcap14) as a microtubule plus-end-tracking protein and as a regulator of microtubule dynamics during neurodevelopment. Gcap14 knockout mice exhibited impaired cortical lamination. Gcap14 deficiency resulted in defective neuronal migration. Moreover, nuclear distribution element nudE-like 1 (Ndel1), an interacting partner of Gcap14, effectively corrected the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency. Finally, we found that the Gcap14-Ndel1 complex participates in the functional link between microtubule and actin filament, thereby regulating their crosstalks in the growth cones of cortical neurons. Taken together, we propose that the Gcap14-Ndel1 complex is fundamental for cytoskeletal remodeling during neurodevelopmental processes such as neuronal processes elongation and neuronal migration.

Prevalence and outcomes of chronic comorbid conditions in patients with sepsis in Korea: a nationwide cohort study from 2011 to 2016.

BACKGROUND: Chronic comorbid conditions are common in patients with sepsis and may affect the outcomes. This study aimed to evaluate the prevalence and outcomes of common comorbidities in patients with sepsis. METHODS: We conducted a nationwide retrospective cohort study. Using data from the National Health Insurance Service of Korea. Adult patients (age ≥ 18 years) who were hospitalized in tertiary or general hospitals with a diagnosis of sepsis between 2011 and 2016 were analyzed. After screening of all International Classification of Diseases 10th revision codes for comorbidities, we identified hypertension, diabetes mellitus (DM), liver cirrhosis (LC), chronic kidney disease (CKD), and malignancy as prevalent comorbidities. RESULTS: Overall, 373,539 patients diagnosed with sepsis were hospitalized in Korea between 2011 and 2016. Among them, 46.7% had hypertension, 23.6% had DM, 7.4% had LC, 13.7% had CKD, and 30.7% had malignancy. In-hospital mortality rates for patients with hypertension, DM, LC, CKD, and malignancy were 25.5%, 25.2%, 34.5%, 28.0%, and 33.3%, respectively, showing a decreasing trend over time (P < 0.001). After adjusting for baseline characteristics, male sex, older age, use of mechanical ventilation, and continuous renal replacement therapy, LC, CKD, and malignancy were significantly associated with in-hospital mortality. CONCLUSIONS: Hypertension is the most prevalent comorbidity in patients with sepsis, and it is associated with an increased survival rate. Additionally, liver cirrhosis, chronic kidney disease, and malignancy result in higher mortality rates than hypertension and DM, and are significant risk factors for in-hospital mortality in patients with sepsis.

Cost-of-illness changes before and after the diagnosis of systemic lupus erythematosus: a nationwide, population-based observational study in Korea.

OBJECTIVES: To estimate the direct healthcare cost progression from before to after systemic lupus erythematosus (SLE) diagnosis and to compare healthcare costs by disease severity. METHODS: Patients with incident SLE diagnosed between 2008 and 2018 were identified from the Korean National Health Insurance database. Annual direct healthcare costs for 5 years before and after SLE were estimated and compared with those of age-, sex-, and calendar month-matched (1:4) controls, without SLE. Direct healthcare costs were compared by disease severity of SLE using regression analysis. RESULTS: Among 11 173 patients with SLE and 45 500 subjects without SLE, annual direct healthcare costs per person increased in the year before SLE diagnosis and peaked in the first year after diagnosis. They were 7.7-fold greater in the SLE patients than in the subjects without SLE ($5,871 vs $759). Severe SLE was associated with 3.284-fold (95% CI 3.075-3.507) higher annual costs than mild SLE during the year after diagnosis. Older age (age 60-79 years), lupus nephritis, interstitial lung diseases, and comorbidities such as avascular necrosis and chronic kidney disease were associated with higher annual direct healthcare costs (times [95% CI]) in the first year after diagnosis; aged 60-69, 1.119 [1.034-1.211], aged 70-79, 1.470 [1.342-1.611], 1.794 [1.711-1.881], 1.435 [1.258-1.638], 6.208 [4.541-8.487], and 1.858 [1.673-2.064], respectively. CONCLUSION: Patients with SLE incurred significantly high direct healthcare costs than subjects without SLE during the first year after diagnosis. Disease severity, older age, major organ involvements and comorbidities were associated with increased healthcare costs.

Risk prediction models incorporating institutional case volume for mortality after hip fracture surgery in the elderly.

INTRODUCTION: While higher institutional case volume is associated with better postoperative outcomes in various types of surgery, institutional case volume has been rarely included in risk prediction models for surgical patients. This study aimed to develop and validate the predictive models incorporating institutional case volume for predicting in-hospital mortality and 1-year mortality after hip fracture surgery in the elderly. MATERIALS AND METHODS: Data for all patients (≥ 60 years) who underwent surgery for femur neck fracture, pertrochanteric fracture, or subtrochanteric fracture between January 2008 and December 2016 were extracted from the Korean National Health Insurance Service database. Patients were randomly assigned into the derivation cohort or the validation cohort in a 1:1 ratio. Risk prediction models for in-hospital mortality and 1-year mortality were developed in the derivation cohort using the logistic regression model. Covariates included age, sex, type of fracture, type of anaesthesia, transfusion, and comorbidities such as hypertension, diabetes, coronary artery disease, chronic kidney disease, cerebrovascular disease, and dementia. Two separate models, one with and the other without institutional case volume as a covariate, were constructed, evaluated, and compared using the likelihood ratio test. Based on the models, scoring systems for predicting in-hospital mortality and 1-year mortality were developed. RESULTS: Analysis of 196,842 patients showed 3.6% in-hospital mortality (7084/196,842) and 15.42% 1-year mortality (30,345/196,842). The model for predicting in-hospital mortality incorporating the institutional case volume demonstrated better discrimination (c-statistics 0.692) compared to the model without the institutional case volume (c-statistics 0.688; likelihood ratio test p value < 0.001). The performance of the model for predicting 1-year mortality was also better when incorporating institutional case volume (c-statistics 0.675 vs. 0.674; likelihood ratio test p value < 0.001). CONCLUSIONS: The new institutional case volume incorporated scoring system may help to predict in-hospital mortality and 1-year mortality after hip fracture surgery in the elderly population.

Effect of Hospital Case-Volume on Mortality after Ovarian Cancer Surgery: A Population-Based Retrospective Cohort Study.

OBJECTIVES: The goal of ovarian cancer surgery has recently shifted from optimal cytoreduction to more complete resection. This study attempted to reassess and update the association between surgical case-volume and both in-hospital and long-term mortality after ovarian cancer surgery using recent data. DESIGN: This study is a population-based retrospective cohort study. Participants/Material: Data from all adult patients who underwent ovarian cancer surgery in Korea between 2005 and 2019 were obtained from the national database. A total of 24,620 patients underwent ovarian cancer surgery in 362 hospitals during the period. SETTING: In-hospital and 1-, 3-, 5-year mortality were set as primary and secondary outcomes. METHODS: Hospitals were categorized into high-volume (>90 cases/year), medium-volume (20-90 cases/year), and low-volume (<20 cases/year) centers considering overall distribution of case-volume. Postoperative in-hospital and long-term mortality were analyzed using logistic regression after adjusting for potential risk factors. RESULTS: Compared to high-volume centers (0.54%), in-hospital mortality was significantly higher in medium-volume (1.40%; adjusted odds ratio, 2.92; confidence interval, 1.82-3.73; p < 0.001) and low-volume (1.61%; adjusted odds ratio, 2.94; confidence interval, 2.07-4.17; p < 0.001) centers. In addition, 1-year mortality was 6.26%, 7.06%, and 7.94% for high-volume, medium-volume, and low-volume centers, respectively, and the differences among the groups were significant. However, case-volume effect was not apparent in 3- and 5-year mortality after ovarian cancer surgery. LIMITATIONS: Lacking clinical information such as staging or histologic diagnosis due to the nature of the administrative data should be considered in interpreting the data. CONCLUSIONS: Case-volume effect was observed for in-hospital and 1-year mortality after ovarian cancer surgery, while it was not clearly found in 3- or 5-year mortality. Dilution of the case-volume effect might be attributed to the high accessibility to care.

COX-2 Inhibitor Use as an Early Treatment Option for Knee Osteoarthritis Patients in Korea: A Population-Based Cross-Sectional Study.

BACKGROUND: To investigate the use of cyclooxygenase-2 (COX-2) inhibitors as an initial drug treatment for knee osteoarthritis (OA) patients. METHODS: From 2013 to 2015, patients with knee OA were identified from the Korean nationwide claims database. Among them, we extracted incident cases of knee OA to identify the initial drug treatment. Trends in the use of non-steroid anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors were analyzed during the first year after their diagnosis. Associated factors for COX-2 inhibitor use were examined using a multivariate logistic regression model. RESULTS: We identified 2,857,999 incident knee OA patients (955,259 in 2013, 981,314 in 2014, and 921,426 in 2015). The mean ± standard deviation age of patients was 64.2 ± 9.8 years. The frequency of COX-2 inhibitor use as initial treatment increased from 3.5% in 2013 to 7.2% in 2015 (P < 0.01). In patients taking the medication regularly for one year after diagnosis (medication possession ratio ≥ 50%), COX-2 inhibitor use also rapidly increased from 5.5% in 2013 to 11.1% in 2015 (P < 0.01). However, the frequencies of non-selective NSAID and analgesic use did not decrease remarkably. Factors associated with patients using COX-2 inhibitors on initial drug treatment were older age (odds ratio [OR], 1.08), female (OR, 1.24), and comorbidity (OR, 1.03). Type of institution, physician speciality, and insurance type of patients were also associated. CONCLUSION: In Korea, COX-2 inhibitors have rapidly increased as an initial treatment for knee OA patients, but it has not appeared to reduce the use of non-selective NSAIDs and analgesics.

Renin-angiotensin system blocker and outcomes of COVID-19: a systematic review and meta-analysis.

BACKGROUND: The association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19. METHODS: We searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease. RESULTS: ACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence). CONCLUSIONS: ACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.

Long-term impacts of appendectomy associated with increased incidence of inflammatory bowel disease, infection, and colorectal cancer.

PURPOSE: Although the appendix has been suggested to play a role in maintaining the gut microbiome and immune system, the ramifications of appendectomy on the development inflammatory bowel disease, sepsis, and colorectal cancer are yet to be determined. The purpose of this study was to evaluate the potential long-term impacts of appendectomy, with a focus on inflammatory bowel disease, infection, and colorectal cancer, using the National Healthcare Insurance Service (NHIS) database of Korea. METHODS: The National Healthcare Insurance Service database in Korea was used for analysis. Adult patients who received appendectomy between 2005 and 2013 were identified. The control group consisted of patients who did not receive appendectomy were matched by baseline characteristics including comorbidities and frequency of healthcare resource utilization. The primary outcome was the incidence-rate ratio (IRR) of Crohn's disease, ulcerative colitis, Clostridium difficile infection, sepsis, and colorectal cancer after appendectomy or the index date. RESULTS: We identified 914,208 patients who underwent appendectomy, and after matching with control patients, a total of 486,844 patients were included for analysis. Patients who underwent appendectomy showed a significantly higher incidence of Crohn's disease (IRR 4.40, 95% confidence interval (CI) 3.78-5.13) and ulcerative colitis (IRR 1.78, 95% CI 1.63-1.93) compared to the control group during the 5-year follow-up period. The associations between appendectomy and Clostridium difficile infection, sepsis, and colorectal cancer were all found to be significant. CONCLUSION: Patients who underwent appendectomy may be at increased risk for developing Crohn's disease, ulcerative colitis, Clostridium difficile infection, sepsis, and colorectal cancer.

Comparisons of Efficacy and Safety between Triple (Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting Beta-Agonist) Therapies in Chronic Obstructive Pulmonary Disease: Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD). OBJECTIVE: Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia. METHOD: We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757). RESULTS: Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0-0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0-0.97]}. CONCLUSION: There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.

The cumulative dose-dependent effects of metformin on the development of tuberculosis in patients newly diagnosed with type 2 diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). Metformin, which is an essential anti-diabetic drug, has been shown to exhibit anti-TB effects in patients with DM. Its effect on preventing the development of TB among patients who are newly diagnosed with DM remains unclear. METHODS: This was a retrospective cohort study using the claims database of the Korean Health Insurance Review and Assessment Service. The study population included patients who were newly diagnosed with type 2 DM and who were treated with anti-diabetic drugs between 1 January 2003 and 31 March 2011. A patient was defined as a metformin user if he/she had taken metformin for more than 28 days within 6 months since cohort entry, and as a metformin non-user if he/she had never been treated with metformin. The development of TB within 2 years after the index date was compared by Cox proportional hazard regression models between metformin users and 1:1 propensity score (PS)-matched non-users. RESULTS: Among 76,973 patients who were newly diagnosed with type 2 DM, 13,396 were classified as metformin users, 52,736 were classified as metformin non-users, and 10,841 were excluded from the final analysis. PS-matched Cox proportional hazard regression models revealed that metformin use was not associated overall with the prevention of TB development (HR 1.17; 95% CI 0.75-1.83; P = 0.482). There was a trend, however, towards a reduction in the development of TB among patients taking a higher cumulative dose of metformin. Patients who were in the highest quartile (Q4) of cumulative metformin dose had only a 10% risk of developing TB compared to metformin non-users. In contrast, during the early phases of metformin treatment, patients in the second quartile (Q2) of cumulative metformin use had a higher risk of developing TB than patients in the first quartile (Q1). CONCLUSIONS: Only the highest cumulative doses of metformin were protective against the development of TB among patients who were newly diagnosed with type 2 DM; lower cumulative doses of metformin did not appear to reduce the incidence of active TB infection.

Effect of Sedatives on In-hospital and Long-term Mortality of Critically Ill Patients Requiring Extended Mechanical Ventilation for ≥ 48 Hours.

BACKGROUND: The purpose of this study was to assess the correlation between sedatives and mortality in critically ill patients who required mechanical ventilation (MV) for ≥ 48 hours from 2008 to 2016. METHODS: We conducted a nationwide retrospective cohort study using population-based healthcare reimbursement claims database. Data from adult patients (aged ≥ 18) who underwent MV for ≥ 48 hours between 2008 and 2016 were identified and extracted from the National Health Insurance Service database. The benzodiazepine group consisted of patients who were administered benzodiazepines for sedation during MV. All other patients were assigned to the non-benzodiazepine group. RESULTS: A total of 158,712 patients requiring MV for ≥ 48 hours were admitted in 55 centers in Korea from 2008 to 2016. The benzodiazepine group had significantly higher in-hospital and one-year mortality compared to the non-benzodiazepine group (37.0% vs. 34.3%, 55.0% vs. 54.4%, respectively). Benzodiazepine use decreased from 2008 to 2016, after adjusting for age, sex, and mean Elixhauser comorbidity index in the Poisson regression analysis (incidence rate ratio, 0.968; 95% confident interval, 0.954-0.983; P < 0.001). Benzodiazepine use, older age, lower case volume (≤ 500 cases/year), chronic kidney disease, and higher Elixhauser comorbidity index were common significant risk factors for in-hospital and one-year mortality. CONCLUSION: In critically ill patients undergoing MV for ≥ 48 hour, the use of benzodiazepines for sedation, older age, and chronic kidney disease were associated with higher in-hospital mortality and one-year mortality. Further studies are needed to evaluate the impact of benzodiazepines on the mortality in elderly patients with chronic kidney disease requiring MV for ≥ 48 hours.

Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis.

BACKGROUND: Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA). METHODS: We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753. RESULTS: We included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia. CONCLUSIONS: The present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more. TRIAL REGISTRATION: This study was prospectively registered in PROSPERO; CRD42019126753.

Estimation of covariance matrix of multivariate longitudinal data using modified Choleksky and hypersphere decompositions.

Linear models are typically used to analyze multivariate longitudinal data. With these models, estimating the covariance matrix is not easy because the covariance matrix should account for complex correlated structures: the correlation between responses at each time point, the correlation within separate responses over time, and the cross-correlation between different responses at different times. In addition, the estimated covariance matrix should satisfy the positive definiteness condition, and it may be heteroscedastic. However, in practice, the structure of the covariance matrix is assumed to be homoscedastic and highly parsimonious, such as exchangeable or autoregressive with order one. These assumptions are too strong and result in inefficient estimates of the effects of covariates. Several studies have been conducted to solve these restrictions using modified Cholesky decomposition (MCD) and linear covariance models. However, modeling the correlation between responses at each time point is not easy because there is no natural ordering of the responses. In this paper, we use MCD and hypersphere decomposition to model the complex correlation structures for multivariate longitudinal data. We observe that the estimated covariance matrix using the decompositions is positive-definite and can be heteroscedastic and that it is also interpretable. The proposed methods are illustrated using data from a nonalcoholic fatty liver disease study.

Small area estimation of receiver operating characteristic curves for ordinal data under stochastic ordering.

There has been a recent increase in the diagnosis of diseases through radiographic images such as x-rays, magnetic resonance imaging, and computed tomography. The outcome of a radiological diagnostic test is often in the form of discrete ordinal data, and we usually summarize the performance of the diagnostic test using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The ROC curve will be concave and called proper when the outcomes of the diagnostic test in the actually positive subjects are higher than in the actually negative subjects. The diagnostic test for disease detection is clinically useful when a ROC curve is proper. In this study, we develop a hierarchical Bayesian model to estimate the proper ROC curve and AUC using stochastic ordering in several domains when the outcome of the diagnostic test is discrete ordinal data and compare it with the model without stochastic ordering. The model without stochastic ordering can estimate the improper ROC curve with a nonconcave shape or a hook when the true ROC curve of the population is a proper ROC curve. Therefore, the model with stochastic ordering is preferable over the model without stochastic ordering to estimate the proper ROC curve with clinical usefulness for ordinal data.

Impact of Mitral Valve Repair Case Volume on Postoperative Mortality　- A Nationwide Korean Cohort Study.

BACKGROUND: Although mitral valve repair is recommended over replacement due to better outcomes, repair rates vary significantly among centers. This study examined the effect of institutional mitral valve repair volume on postoperative mortality.Methods and Results:All cases of adult mitral valve repair performed in Korea between 2009 and 2016 were analyzed. The association between case volume and 1-year mortality was analyzed after categorizing centers according to the number of mitral valve repairs performed as low-, medium-, or high-volume centers (<20, 20-40, and >40 cases/year, respectively). The effect of case volume on cumulative all-cause mortality was also assessed. In all, 6,041 mitral valve repairs were performed in 86 centers. The 1-year mortality in low-, medium-, and high-volume centers was 10.1%, 8.7%, and 4.7%, respectively. Low- and medium-volume centers had increased risk of 1-year mortality compared with high-volume centers, with odds ratios of 2.80 (95% confidence interval [CI] 2.15-3.64; P<0.001) and 2.66 (95% CI 1.94-3.64; P<0.001), respectively. The risk of cumulative all-cause mortality was also worse in low- and medium-volume centers, with hazard ratios of 1.96 (95% CI 1.68-2.29; P<0.001) and 1.77 (95% CI 1.47-2.12; P<0.001), respectively. CONCLUSIONS: Lower institutional case volume was associated with higher mortality after mitral valve repair. A minimum volume standard may be required for hospitals performing mitral valve repair to guarantee adequate outcome.

Increased risk of malignancy in patients aged over 50 with idiopathic inflammatory myositis compared to patients with osteoarthritis of the knee.

Objectives: To estimate risk of malignancy in patients with idiopathic inflammatory myositis (IIM) compared to patients with knee osteoarthritis (OA).Methods: Patients with IIM and knee OA aged over 50, who had no history of malignancy, were identified using Korean National claims database from January 2012 to December 2014. They had been observed until a malignancy was diagnosed or up to the end of the study, December 2015. The incidence rate (IR) of malignancy in IIM patients was calculated and compared with knee OA patients using standardized incidence ratio (SIR).Results: A total of 634 polymyositis (PM) and 556 dermatomyositis (DM) patients were included. Overall, 100 solid (IR 270.4/10,000 person-years (PY), 95% confidence interval (CI) 217.4-323.4) and 12 hematologic malignancies (IR 32.4/10,000 PY, 95% CI 14.1-50.8) occurred. Compared with knee OA, risk of overall (SIR 1.5, 95% CI 1.2-1.8), solid (SIR 1.4, 95% CI 1.1-1.6), and hematologic malignancy (SIR 5.7, 95% CI 2.5-9.0) were increased in IIM patients. This was due to increased incidence of malignancy in DM (hematologic malignancy, SIR 8.7, 95% CI 2.7-14.7, solid malignancy, SIR 1.5, 95% CI 1.1-1.9).Conclusion: Patients with IIM, especially DM, have an increased risk of malignancy compared to patients with knee OA.

Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis.

BACKGROUND: Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. METHODS AND FINDINGS: We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. CONCLUSIONS: These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

Incidence and Outcomes of Sepsis in Korea: A Nationwide Cohort Study From 2007 to 2016.

OBJECTIVES: This study aimed to estimate the incidence and clinical outcomes of sepsis in Korea from 2007 to 2016. DESIGN: Retrospective observational study. SETTING: Nationwide study with population-based healthcare reimbursement claims database. PATIENTS: Using data from the National Health Insurance Service of Korea, patients who were hospitalized with a diagnosis of sepsis from 2007 to 2016 were analyzed. The incidence of sepsis was calculated using mid-year census population and analyzed according to year, age, and sex. The Elixhauser Comorbidity Index score was calculated to adjust for the impact of comorbidities on clinical outcome. In-hospital mortality, hospital length of stay, ICU admission rates, and risk factors for in-hospital mortality were also analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence of sepsis increased from 173.8 per 100,000 population in 2007 to 233.6 per 100,000 population in 2016. In-hospital mortality decreased from 30.9% in 2007 to 22.6% in 2016 (p < 0.0001). From 2007 to 2016, hospital length of stay and ICU admission rates associated with sepsis decreased from 26.0 ± 33.5 days to 21.3 ± 24.4 days (p < 0.0001) and from 16.2% to 12.7% (p < 0.0001), respectively. Male sex, age greater than 50 years, Elixhauser Comorbidity Index greater than 10, and mechanical ventilation were identified as risk factors for in-hospital mortality after adjusting for baseline characteristics. CONCLUSIONS: The incidence of sepsis in Korea increased from 2007 to 2016, while the associated in-hospital mortality, hospital length of stay, and ICU admission rates decreased.

Malignancy risk in Korean male patients with ankylosing spondylitis.

The objective of this study is to determine the overall and specific cancer risks in male patients with ankylosing spondylitis (AS). From the claims database of the Health Insurance and Review Assessment, male patients with AS without prior cancer history were selected (n = 21,780). Stratified random samples of claims data were used as a reference general male population group (n = 342,361). Incidence rates of overall and types of cancer were presented as number of events per 10,000 person-years with 95% confidence interval (CI). A standardized incidence ratio (SIR) was used to represent the association between AS and cancer, accounting for person-years at risk. Compared to a general male population group, the overall incidence of cancer was increased in male patients with AS (SIR 1.25, 95% CI 1.15-1.36). For specific malignancy types, the risks of male reproductive system malignancy (SIR 1.97, 95% CI 1.59-2.35) and pancreatic cancer (SIR 1.75, 95% CI 1.12-2.37) were increased. Male patients with AS had increased cancer risk, especially for male reproductive system and pancreatic cancer.

Effect of Institutional Kidney Transplantation Case-Volume on Post-Transplant Graft Failure: a Retrospective Cohort Study.

BACKGROUND: The impact of institutional case volume to graft failure rate after adult kidney transplantation is relatively unclear compared to other solid organ transplantations. METHODS: A retrospective cohort study of 13,872 adult kidney transplantations in Korea was performed. Institutions were divided into low- (< 24 cases/year), medium- (24-60 cases/year), and high- (> 60 cases/year) volume centers depending on the annual case volume. One-year graft failure rate was defined as the proportion of patients who required dialysis or re-transplantation at one year after transplantation. Postoperative in-hospital mortality and long-term graft survival were also measured. RESULTS: After adjustment, one year graft failure was higher in low-volume centers significantly (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.26-1.78; P < 0.001) and medium-volume centers (aOR, 1.87; 95% CI, 1.57-2.23; P < 0.001) compared to high-volume centers. Low-volume centers had significantly higher mortality (aOR, 1.75; 95% CI, 1.15-2.66; P = 0.01) than that of high-volume centers after adjustment. Long-term graft survival of up to 9 years was superior in high-volume centers compared to low- and medium-volume centers (P < 0.001). CONCLUSION: Higher-case volume centers were associated with lower one-year graft failure rate, lower in-hospital mortality, and higher long-term graft survival after kidney transplantation.