Analysis of the waitlist performance and post-transplant outcomes of lung transplant in elderly recipients in Korea: A nationwide cohort study.

BACKGROUND: There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea. METHODS: We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023. RESULTS: In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4 vs. 75.4%; p = .004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p = .004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p < .001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ2 = 8.302, p = .016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ2 = 9.056, p = .029). CONCLUSION: The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes.

Social media has become a mainstream source of medical information for patients with rheumatic diseases: a cross-sectional survey of patients.

This study analyzed the status of medical information acquisition through social media (SM) and its impact on healthcare utilization among patients with rheumatic diseases (RDs) who visited the rheumatology department of a tertiary hospital. We consecutively evaluated 102 patients with RDs in this single-center cross-sectional survey. Using a face-to-face survey, patients were asked about the sources they used to acquire medical information, factors influencing their visits to tertiary hospitals, and the potential impact of acquiring medical information on RDs through SM. SM refers to YouTube, Facebook, Instagram, Kakao Channel, Naver Band, and X. The mean age was 42.3 years and 39% were female. The most common disease was ankylosing spondylitis (45.1%), followed by rheumatoid arthritis (20.6%). The most frequent method for acquiring medical information regarding RDs, except for rheumatologists, was internet portal sites (47.8%), followed by SM (40.2%). The most important factor influencing the decision to visit a tertiary hospital was medical doctors (51%); only 1% of the patients responded that SM was the most crucial factor in determining their visit. Most patients (77.5%) responded that acquiring medical information through SM would help them manage their diseases. Our data revealed that a substantial proportion of patients with RDs obtained medical information through SM. However, the impact of SM on visiting a tertiary hospital was minimal, suggesting that SM has become a mainstream source of medical information, yet the reliability of SM remains relatively low. Rheumatology societies should establish SM platforms capable of providing high-quality medical information.

FAT10 differentially stabilizes MYPT2 isoforms.

Myosin phosphatase (MP) is an enzyme complex that regulates muscle contraction and plays important roles in various physiological and pathological conditions. Myosin phosphatase targeting subunit (MYPT) 2, a subunit of MP, interacts with protein phosphatase 1c to regulate its phosphatase activity. MYPT2 exists in various isoforms that differ in the composition of essential motifs that contribute to its function. However, regulatory mechanisms underlying these isoforms are poorly understood. Human leukocyte antigen-F adjacent transcript 10 (FAT10) is a ubiquitin-like modifier that not only targets proteins for proteasomal degradation but also stabilizes its interacting proteins. In this study, we investigated the effect of the interaction between FAT10 and MYPT2 isoform a (the canonical full-length form of MYPT2) or MYPT2 isoform f (the natural truncated form of MYPT2). FAT10 interacted with both MYPT2 isoforms a and f; however, only MYPT2 isoform f was increased by FAT10, whereas MYPT2 isoform a remained unaffected by FAT10. We further confirmed that, in contrast to MYPT2 isoform a, MYPT2 isoform f undergoes rapid degradation via the ubiquitin-proteasome pathway and that FAT10 stabilizes MYPT2 isoform f by inhibiting its ubiquitination. Therefore, our findings suggest that the interaction between FAT10 and MYPT2 isoforms leads to distinct stabilization effects on each isoform, potentially modulating MP activity.

Erratum: Correction of Author's Affiliation in the Article "Changing Patterns of Medical Visits and Factors Associated With No-show in Patients With Rheumatoid Arthritis During COVID-19 Pandemic".

This corrects the article on p. e423 in vol. 35, PMID: 33316859.

Maternal and paternal effects on hyperuricaemia: a cross-sectional study from the seventh Korean National Health and Nutrition Examination Survey.

OBJECTIVE: As the heritability of hyperuricaemia remains largely unexplained, we analysed the association between parental and offspring hyperuricaemia at the phenotype level. METHODS: This cross-sectional study included data on 2373 offspring and both-parent pairs from the seventh Korean National Health and Nutrition Examination Survey. Logistic regression and generalised estimating equation analysis were used to evaluate the association between offspring and parental hyperuricaemia adjusting for metabolic risk factors and alcohol intake. RESULTS: Both maternal and paternal hyperuricaemia were associated with offspring hyperuricaemia among teenagers, but from the age of 20 years, a strong association was observed between offspring and paternal, rather than, maternal hyperuricaemia, and this could not be explained by metabolic risk factors such as obesity. However, there was a positive interaction between offspring alcohol intake and parental hyperuricaemia, and there was a stronger association between terciles of offspring alcohol intake and hyperuricaemia in the presence of parental hyperuricaemia: T1 (reference), T2 odds ratio (OR) 1.1 (0.3-4.6), and T3 OR 3.3 (1.4-7.9) (P for trend .017) vs. T1 (reference), T2 OR 0.7 (0.3-1.9), and T3 OR 1.1 (0.6-2.2) (P for trend .974). CONCLUSION: These results suggest a gene-environment interaction, especially with respect to alcohol intake for hyperuricaemia in Korean adults.

Associations of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Monocyte-to-Lymphocyte Ratio with Osteoporosis and Incident Vertebral Fracture in Postmenopausal Women with Rheumatoid Arthritis: A Single-Center Retrospective Cohort Study.

Background and Objectives: We investigated whether nutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphoycte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are associated with the presence of osteoporosis (OP) and vertebral fractures in patients with rheumatoid arthritis (RA). Materials and Methods: This retrospective cohort study included 413 postmenopausal patients with RA and 200 healthy controls who underwent dual-energy X-ray absorptiometry (DEXA) between January 2005 and December 2017. DEXA examination data were defined as the index date, and all laboratory values were measured within one month from the index date. OP was defined as a T-score < −2.5, and incident vertebral fractures were defined as the first occurrence of non-traumatic fractures after the index date. NLR, PLR, and MLR measures were dichotomized by a median split (low vs. high). Results: The median NLR, PLR, and MLR in RA patients were significantly higher than those in controls. The frequencies of OP of the lumbar spine, hip, and either site in postmenopausal patients with RA were 24.7%, 15.5%, and 32%, respectively, and were significantly higher than those in controls. After adjusting for confounding factors, a high baseline NLR was significantly associated with OP at either site (OR = 1.61, p = 0.041). In addition, high baseline NLR (OR = 2.11, p = 0.025) and PLR (OR = 2.3, p = 0.011) were related with the presence OP at hip. During the follow-up period, 53 (12.8%) patients with RA developed vertebral fractures incidentally. In multivariable Cox regression models, a high baseline NLR (HR = 4.72, p < 0.001), PLR (HR = 1.96, p = 0.024), and MLR (HR = 2.64, p = 0.002) were independently associated with a higher risk of incidental vertebral fractures. Conclusions: Our data suggest that NLR, PLR, and MLR can be used as potential markers of systemic bone loss among individuals with RA.

Clinically amyopathic dermatomyositis presenting with isolated facial edema complicated by acute respiratory failure: a case report.

BACKGROUND: In clinically amyopathic dermatomyositis, the hallmark cutaneous manifestations are the key to diagnosis. We report a case of clinically amyopathic dermatomyositis which presented with facial edema as the sole cutaneous manifestation and was later complicated by acute respiratory failure leading to death. CASE PRESENTATION: A 58-year-old woman presented with edema of the face that had developed approximately one year ago. There was no weakness in the extremities, and the serum creatine kinase level was within normal range. On MRI, there was diffuse edematous change in the bilateral masticator and extra-ocular muscles, accompanied by subcutaneous fat infiltration in the face. A shared decision was made to defer muscle biopsy in the facial muscles. The facial swelling almost resolved with medium-dose glucocorticoid therapy but relapsed in days at glucocorticoid doses lower than 15 mg/day. Combination therapy with either azathioprine, mycophenolate, or methotrexate was not successful in maintaining clinical remission, and the swelling became more severe after relapses. A US-guided core-needle biopsy was subsequently performed in the right masseter muscle. On pathologic examination, there was a patchy CD4 + T cell-dominant lymphoplasmacytic infiltration in the stroma, necrosis of the myofibrils and prominent perifascicular atrophy. Based on those findings, a diagnosis of clinically amyopathic dermatomyositis was made. Therapy with gamma-globulin was not effective in maintaining remission. In the sixth week after starting rituximab, she presented to emergency room with altered mental state from acute respiratory failure. Despite treatment with antibiotics, glucocorticoid pulse, cyclosporin, and polymyxin B-immobilized fiber column direct hemoperfusion, she died three weeks later from persistent hypoxemic respiratory failure. CONCLUSIONS: This case showed the full spectrum and severity of internal organ involvement of dermatomyositis, although the patient presented exclusively with subcutaneous edema limited to the head. The prognosis may be more closely associated with a specific auto-antibody profile than the benign-looking initial clinical manifestation. Close follow-up of lung involvement with prophylactic treatment for Pneumocystis pneumonia and prompt implementation of emerging therapeutic regimens may improve the outcome.

Coronavirus Disease 19 (COVID-19) complicated with pneumonia in a patient with rheumatoid arthritis receiving conventional disease-modifying antirheumatic drugs.

In December 2019, numerous coronavirus disease 2019 (COVID-19) cases were reported in Wuhan, China, which has since spread throughout the world. However, its impact on rheumatoid arthritis (RA) patients is unknown. Herein, we report a case of COVID-19 pneumonia in a 61-year-old female RA patient who was receiving conventional disease-modifying antirheumatic drugs (cDMARDs). The patient presented with a 4-day history of myalgia and febrile sensation. COVID-19 was confirmed by real-time polymerase chain reaction (PCR). Chest X-ray showed increased opacity on the right lower lung area, and C-reactive protein level was slightly elevated. The patient was treated with antiviral agents (lopinavir/ritonavir), and treatment with cDMARDs was discontinued except hydroxychloroquine. Her symptoms and laboratory results gradually improved. Three weeks later, real-time PCR for COVID-19 showed negative conversion, and the patient was discharged without any complications.

Platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as potential makers for digital ulcers and interstitial lung disease in patients with systemic sclerosis: cross-sectional analysis of data from a prospective cohort study.

In this study, we aimed to investigate the association of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) with clinical manifestations in patients with systemic sclerosis (SSc). We conducted a cross-sectional analysis of data collected from a cohort study of 114 female patients with SSc and of 304 age-matched, healthy, female controls recruited from a tertiary rheumatology center. Patients with digital ulcers (DU) included those with either active or healed ulcers. Interstitial lung disease (ILD) was diagnosed on detection of diffuse ground-glass opacity or pulmonary fibrosis on chest X-ray or on high-resolution computed tomography. Patients with SSc had significantly higher PLR and NLR than ealthy controls. Of 114 patients with SSc, 35 (30.7%) and 54 (47.4%) patients had DU (active: 12, healed: 23) and ILD, respectively. PLR and NLR in SSc patients with concurrent DU or ILD were significantly higher than that in those without these respective complications. The PLR (OR = 1.008, 95% CI 1.002-1.015), but not the NLR, was independently associated with the presence of DU in SSc patients, based on multivariable logistic regression models. Additionally, both PLR (OR = 1.008, 95% CI 1.001-1.014) and NLR (OR = 1.515, 95% CI 1.066-2.155) correlated independently with the presence of ILD. However, both the PLR and NLR showed no significant association with the modified Rodnan skin score, pulmonary arterial hypertension, and gastrointestinal involvement. Our results suggest that PLR and NLR could be considered as potential biomarkers of DU and ILD, in patients with SSc.

Changing Patterns of Medical Visits and Factors Associated with No-show in Patients with Rheumatoid Arthritis during COVID-19 Pandemic.

BACKGROUND: The main barrier to the effective rheumatoid arthritis (RA) therapy is poor adherence. Coronavirus disease 2019 (COVID-19) pandemic have led to a significant change in the pattern and the number of medical visits. We assessed changing patterns of medical visits and no-show, and identified factors associated with no-show in patients with RA during COVID-19 pandemic. METHODS: RA patients treated with disease-modifying antirheumatic drugs at least 6 months who had been in remission or those with mild disease activity were observed for 6 months from February to July 2020. No-show was defined as a missed appointment that was not previously cancelled by the patient and several variables that might affect no-show were examined. RESULTS: A total of 376 patients and 1,189 appointments were evaluated. Among 376 patients, 164 patients (43.6%) missed appointment more than one time and no-show rate was 17.2% during COVID-19 pandemic. During the observation, face-to-face visits gradually increased and no-show gradually decreased. The logistic regression analysis identified previous history of no-show (adjusted odds ratio [OR], 2.225; 95% confidence interval [CI], 1.422-3.479; P < 0.001) and fewer numbers of comorbidities (adjusted OR, 0.749; 95% CI, 0.584-0.961; P = 0.023) as the independent factors associated with no-show. CONCLUSION: Monthly analysis showed that the no-show rate and the pattern of medical visits gradually changed in patients with RA during COVID-19 pandemic. Moreover, we found that previous history of no-show and fewer numbers of comorbidities as the independent factors associated with no-show.

Dietary and nutritional factors associated with hyperuricemia: The seventh Korean National Health and Nutrition Examination Survey.

BACKGROUND AND OBJECTIVES: The association of dietary and nutritional factors with hyperuricemia and gout is well-known in Western populations. The present study aimed to examine the association of dietary and nutritional factors with hyperuricemia among Korean adults. METHODS AND STUDY DESIGN: This cross-sectional study included 10,175 participants from the seventh Korean National Health and Nutrition Examination Survey 2016-2017. Dietary information was collected using a single 24-hour recall method, and nutritional information was derived from the 9th Korean Food Composition Table. The associations between serum uric acid and intake of meat, seafoods, nuts, and legumes, sugar-sweetened products, dairy products, alcohol, sodium, vitamin A, vitamin B1, vitamin C, and dietary fiber were analyzed using linear regression analysis adjusting for confounding variables. The association with hyperuricemia was analyzed using logistic regression analysis. All analyses were weighted by the sampling design. RESULTS: Alcohol intake was associated with serum uric acid in both men and women. In men, the highest quartile of alcohol intake was associated with a 1.5-times higher prevalence of hyperuricemia (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.16-1.95), while vitamin C and dietary fiber intakes were found to be inversely associated with hyperuricemia. For vitamin C and dietary fiber intake, the ORs for a quartile increase were 0.93 (95% CI 0.86-0.99) and 0.92 (95% CI 0.85-0.99), respectively. CONCLUSIONS: The associations between vitamin C, dietary fiber and alcohol intakes and hyperuricemia in men support the Dietary Approach to Stop Hypertension (DASH)-based approach and attention to alcohol intake for managing hyperuricemia in Korean men.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as predictors of 12-week treatment response and drug persistence of anti-tumor necrosis factor-α agents in patients with rheumatoid arthritis: a retrospective chart review analysis.

Data are scarce regarding the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with treatment response and persistence of anti-TNF-α agents in patients with rheumatoid arthritis (RA). Thus, we investigated whether baseline NLR and PLR could predict 12-week treatment response and long-term persistence of anti-TNF-α agents in RA patients. This is a retrospective chart review analysis of 82 women with RA who started anti-TNF-α agents as the first-line biologic therapy and 328 healthy age-matched women. RA patients were divided into high and low baseline NLR or PLR subgroups using the median split. European League against Rheumatism (EULAR) treatment response was evaluated at 12 weeks. RA patients had significantly higher NLR and PLR than controls. High baseline NLR and PLR groups showed higher 12-week EULAR non-response rate than low NLR (30% vs 7.1%, p = 0.01) and PLR groups (27.5% vs 9.5%, p = 0.047), respectively. After adjusting for confounding factors, high baseline NLR (OR 5.57, p = 0.014) and PLR (OR 4.24, p = 0.04) were significantly associated with a higher risk of EULAR non-response at 12 weeks. During the study period, 47 (57.3%) RA patients (lack of efficacy: n = 31; adverse events: n = 16) discontinued anti-TNF-α agents. High baseline NLR was associated with an increased risk of anti-TNF-α agent withdrawal due to lack of efficacy (HR 2.12, p = 0.045). Our data suggest that baseline NLR and PLR are useful markers for predicting the treatment outcome of anti-TNF-α agents in RA patients.

Increased serum uric acid levels are associated with digital ulcers in patients with systemic sclerosis.

Endothelial injury/dysfunction is thought to be one of the earliest events in the development of vascular diseases in systemic sclerosis (SSc). Although hyperuricemia is also known to induce endothelial dysfunction and vascular inflammation, the effect of uric acid on the microvascular involvement in SSc has not been well established. We investigated whether increased serum uric acid (SUA) levels are associated with digital ulcers (DUs) in SSc. In this cross-sectional study, we consecutively recruited 71 women with SSc and 349 age- and sex-matched healthy subjects, and SUA levels were measured in all study subjects. SSc patients had significantly higher mean SUA levels than healthy subjects (4.5 ± 1 mg/dL vs 4.2 ± 0.9 mg/dL, p = 0.017), although a significantly lower body mass index (BMI) was observed in SSc patients than in controls. Among 71 SSc patients, 22 (31%) had DUs ever (active DUs, 8; healed DUs, 14). SSc patients presenting with DUs ever showed significantly higher SUA levels than those without this feature (median, 5.2 mg/dL vs 4.1 mg/dL, p = 0.009). In multivariable logistic regression models adjusted for confounders such as BMI and estimated glomerular filtration rate, increased SUA levels were associated with a significantly higher risk for the presence of DUs ever (OR 2.3, 95% CI 1.16-4.57, p = 0.018). Our data revealed that elevated SUA levels are independently associated with the presence of DUs in SSc patients, thereby suggesting the potential role of hyperuricemia in the pathogenesis of SSc vasculopathy.

Long-term adherence and persistence with febuxostat among male patients with gout in a routine clinical setting.

Objectives: To assess long-term adherence and persistence to febuxostat (FBX) and factors that might contribute to non-adherence and non-persistence to FBX in male patients with gout during a 3-year period. Methods: Adherence to FBX was assessed by the clinic nurses through pill counts at the scheduled visits and non-adherence was defined as less than 80% of the prescribed dose taken. Non-persistence was defined as discontinuation of FBX longer than 60 days. Results: A total of 220 patients were recruited. The percentage of adherence and persistence was 71.8% and 80.9% at 1 year, 65.5% and 68.2% at 2 years and 58.2% and 56.4% at 3 years, respectively. The logistic regression analysis identified high income status, current smoking, absence of hypertension and previous history of non-persistence with urate-lowering therapy (ULT) as the independent factors associated with non-adherence, and the unmarried, absence of hypertension and previous history of non-persistence with ULT as the independent factors associated with non-persistence. Conclusion: Variable risk factors that are correlated with poor adherence or persistence and easily assessed can be used to identify patients at a particular risk of poor adherence or persistence.

Interleukin-33 acts as a transcriptional repressor and extracellular cytokine in fibroblast-like synoviocytes in patients with rheumatoid arthritis.

The present study aimed to assess the functions of interleukin (IL)-33 in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assays (ELISAs) were used to quantify interleukin (IL)-33 in plasma obtained from patients with RA and osteoarthritis (OA). To evaluate functions of intracellular IL-33, levels of inflammatory mediators and matric metalloproteinases (MMPs) were measured in RA FLS transfected with IL-33 small- interfering RNA (siRNA) or plasmids, and changes in the expression and regulation of nuclear factor kappaB (NF-κB) were determined using western blotting and reporter gene assays. In addition, to examine the extracellular effects of IL-33, IP10 and receptor activator of NF-κB ligand (RANKL) mRNA levels were measured after treatment with IL-33 and blocking antibodies to ST2, the IL-33 receptor. To evaluate whether extracellular IL-33 regulated osteoclastogenesis, human CD14(+) monocytes cocultured with IL-33-stimulated FLS were stained with tartrate-resistant acid phosphatase (TRAP). IL-33 levels were higher in plasma obtained from patients with RA than in those obtained from patients with OA. The expression levels of IL-33 were elevated in RA FLS that had been stimulated with poly I:C, IL-1ß, and tumor necrosis factor (TNF)-α. Silencing of IL-33 increased the levels of pro-inflammatory molecules and MMPs, promoted inhibitor of kappaB (IκBα) degradation, and increased NF-κB activity; these effects were reversed in IL-33 plasmid-transfected FLS. Stimulation with exogenous IL-33 increased RANKL and IP-10 mRNA expression. These increases were blocked by anti-ST2 treatment. Furthermore, we confirmed that extracellular IL-33 stimulated the formation of TRAP(+) multinucleated osteoclasts through RA FLS. These results suggested that intracellular IL-33 acted as a transcriptional repressor of NF-κB, which may provide negative feedback against inflammatory responses, whereas, extracellular IL-33 functioned as an activator of osteoclastogenesis. Therefore, increased plasma IL-33 levels in patients with RA could be a possible biomarker to reflect the potential risks of bone erosion.

Adherence with urate-lowering therapies among male patients with gout in a routine clinical setting.

OBJECTIVES: To assess adherence (compliance and persistence) and factors that might contribute to nonadherence to urate-lowering therapies (ULT) in patients with gout in a routine clinical setting. METHODS: This prospective observational cohort study was conducted in the rheumatology center of a local tertiary hospital. A total of 132 male adults aged 75 years or younger who were incidentally diagnosed with gout were included. Adherence to ULT was assessed by the clinic nurses through pill counts. RESULTS: Of the 132 patients, 94 (71.2%) was compliant and 81 (61.4%) was persistent with ULT. The logistic regression analysis revealed that the absence of chronic kidney disease (CKD) and the previous history of non-persistence with ULT are the independent factors associated with noncompliance and the absence of CKD is an independent factor associated with non-persistence. The average serum urate levels of the noncompliant (p = 0.001) and non-persistent (p = 0.002) patients were significantly higher than those of the compliant and persistent patients. CONCLUSIONS: The absence of CKD and the previous history of non-persistence of ULT that are correlated with poor adherence and easily assessed can be used to identify patients at a particular risk of poor adherence.

Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus.

High-dose steroids, immunosuppressants such as cyclophosphamide and cyclosporine, and high-dose intravenous immunoglobulin have all been used to control hemophagocytic lymphohistiocytosis (HLH) or autoimmune hemolytic anemia (AIHA) associated with systemic lupus erythematosus (SLE); however, some patients are refractory to treatment. Rituximab has successfully resolved many of the refractory manifestations of SLE. Here, we report a case of HLH and AIHA associated with SLE that was refractory or intolerable to conventional therapy, but was successfully treated with rituximab.

DA-9601 has protective effects comparable to those of proton pump inhibitor and rebamipide against nonsteroidal anti-inflammatory drugs-induced upper and lower gastrointestinal bleeding in patients with rheumatoid arthritis: A nationwide study using Korean Health Insurance Review and Assessment Service database.

DA-9601 extracted from Artemisia asiatica contains a bioactive compound - eupatilin - that can protect against gastric mucosal damage through anti-inflammatory and anti-oxidative properties and is approved for treating acute and chronic gastritis in Korea, but their ability to protect gastrointestinal (GI) bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is unclear. We aimed to compare the protective effects of DA-9601 to those of proton pump inhibitors (PPI) and rebamipide against upper and lower GI bleeding in patients with rheumatoid arthritis (RA) undergoing long-term NSAIDs therapy using the Korean Health Insurance Review and Assessment database. In this nationwide retrospective cohort study, we evaluated patients with RA who concurrently received NSAIDs for >3 months with DA-9601, PPI, or rebamipide between January 2015 and December 2017. The index date was the date of NSAIDs initiation, and all patients were followed up until December 2020 to detect upper and lower GI bleeding. In total, 24,258 patients with RA were eligible, and 5468 (22.5%), 4417 (18.2%), and 14,373 (59.3%) received DA-9601, PPI, or rebamipide, respectively, on the index date. During follow-up, upper and lower GI bleeding occurred in 508 (2.1%) and 402 (1.6%) patients with RA, respectively. The incidence rate of upper and lower GI bleeding was 615/100,000 and 485/100,000 person-years, respectively. Among patients with RA receiving DA-9601, PPI, or rebamipide, the frequencies of NSAIDs-induced upper GI bleeding were 0.5%, 0.4%, and 1.2%, respectively. The frequencies of NSAIDs-induced lower GI bleeding were 0.4%, 0.4%, and 0.9%, respectively. The incidence of NSAIDs-induced upper GI bleeding in patients with RA receiving DA-9601, PPI, and rebamipide was 601/100,000, 705/100,000, and 596/100,000 person-years, respectively, while the incidence of NSAIDs-induced lower GI bleeding in the same groups was 449/100,000, 608/100,000, and 465/100,000 person-years, respectively. In the multivariate Cox regression analysis, no significant difference was observed in lower and upper GI bleeding hazards between patients with RA using DA-9601, PPI, and rebamipide. Our results suggest that DA-9601 may exhibit protection against NSAIDs-induced GI bleeding that is comparable to those of PPI and rebamipide in patients with RA.

Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.

INTRODUCTION: Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. METHODS: In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. RESULTS: TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR 2.84, p = 0.02). CONCLUSION: In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.

Unique Changes in the Lung Microbiome following the Development of Chronic Lung Allograft Dysfunction.

The importance of lung microbiome changes in developing chronic lung allograft dysfunction (CLAD) after lung transplantation is poorly understood. The lung microbiome-immune interaction may be critical in developing CLAD. In this context, examining alterations in the microbiome and immune cells of the lungs following CLAD, in comparison to the lung condition immediately after transplantation, can offer valuable insights. Four adult patients who underwent lung retransplantation between January 2019 and June 2020 were included in this study. Lung tissues were collected from the same four individuals at two different time points: at the time of the first transplant and at the time of the explantation of CLAD lungs at retransplantation due to CLAD. We analyzed whole-genome sequencing using the Kraken2 algorithm and quantified the cell fractionation from the bulk tissue gene expression profile for each lung tissue. Finally, we compared the differences in lung microbiome and immune cells between the lung tissues of these two time points. The median age of the recipients was 57 years, and most (75%) had undergone lung transplants for idiopathic pulmonary fibrosis. All patients were administered basiliximab for induction therapy and were maintained on three immunosuppressants. The median CLAD-free survival term was 693.5 days, and the median time to redo the lung transplant was 843.5 days. Bacterial diversity was significantly lower in the CLAD lungs than at transplantation. Bacterial diversity tended to decrease according to the severity of the CLAD. Aerococcus, Caldiericum, Croceibacter, Leptolyngbya, and Pulveribacter genera were uniquely identified in CLAD, whereas no taxa were identified in lungs at transplantation. In particular, six taxa, including Croceibacter atlanticus, Caldiserium exile, Dolichospermum compactum, Stappia sp. ES.058, Kinetoplastibacterium sorsogonicusi, and Pulveribacter suum were uniquely detected in CLAD. Among immune cells, CD8+ T cells were significantly increased, while neutrophils were decreased in the CLAD lung. In conclusion, unique changes in lung microbiome and immune cell composition were confirmed in lung tissue after CLAD compared to at transplantation.