Purpose: The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity. Materials and Methods: We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire. Results: We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported. Conclusion Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Purpose: The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity. Materials and Methods: We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire. Results: We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported. Conclusion Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.

Purpose: The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking. Materials and Methods: In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2. Results: There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples. Conclusion Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated. Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).

Objective: In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Methods: Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Results: Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07–1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89–0.98, P=0.0050). Conclusions According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background/Aims: To determine the effectiveness of tyrosine kinase inhibitor (TKI) plus reduced-intensity therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), this retrospective study compared treatment outcomes and induction mortality according to backbone regimen intensity. Methods: The data of 132 patients diagnosed with Ph-positive ALL were retrospectively collected from five centers. Patients received imatinib plus intensive chemotherapy (modified VPD, KALLA1407, or hyper-CVAD) or reduced-intensity chemotherapy (EWALL) for curative purposes. This study analyzed 117 patients, of which 35,22,46, and 14 received modified VPD, KALLA1407, hyper-CVAD, and EWALL, respectively. All patients used imatinib as a TKI. Results: The median age of the patients who received reduced-intensity chemotherapy was 64.4 years, while that of the patients with intensive regimens was 47.5 years. There was no induction death in the reduced-intensity group, while nine patients died in the intensive therapy group. Major molecular response achievement tended to be higher in the intensive chemotherapy group than in the reduced-intensity group. More patients in the intensive chemotherapy group received allogeneic stem cell transplantation (allo-SCT). There was no statistically significant difference in long-term survival between the two groups in terms of relapse-free survival and overall survival rates. Conclusions When imatinib plus reduced-intensity therapy was used as a frontline treatment, there was no inferiority in obtaining complete remission compared to imatinib plus intensive chemotherapy or significant difference in long-term survival. Since imatinib plus reduced-intensity therapy has limitations in obtaining a deep molecular response, proceeding to allo-SCT should be considered.