Background: Allogeneic hematopoietic stem cell transplantation (HSCT) was not actively performed in elderly acute myeloid leukemia (AML) or myelodysplastic syndrome patients who are at a high-risk based on hematopoietic cell transplantation-specific comorbidity index (HCT-CI). The advent of reduced-intensity conditioning (RIC) regimens has made HSCT applicable in this population. However, the selection of appropriate conditioning is a major concern for the attending physician. The benefits of combination of treosulfan and fludarabine (Treo/Flu) have been confirmed through many clinical studies. Korean data on treosulfan-based conditioning regimen are scarce. Methods: A retrospective study was conducted to compare the clinical outcomes of allogeneic HSCT using RIC between 13 patients receiving Treo/Flu and 39 receiving busulfan/ fludarabine (Bu/Flu). Results: In terms of conditioning-related complications, the frequency of ≥ grade 2 nausea or vomiting was significantly lower and the duration of symptoms was shorter in the Treo/ Flu group than in the Bu/Flu group. The incidence of ≥ grade 2 mucositis tended to be lower in the Treo/Flu group. In the analysis of transplant outcomes, all events of acute graft versus host disease (GVHD) and ≥ grade 2 acute GVHD occurred more frequently in the Treo/ Flu group. The frequency of Epstein-Barr virus reactivation was significantly higher in the Treo/Flu group (53.8% vs. 23.1%, P = 0.037). Non-relapse mortality (NRM) at 12 months was higher in the Treo/Flu group (30.8% vs. 7.7%, P = 0.035). Significant prognostic factors included disease type, especially secondary AML, disease status and high-risk based on HCT-CI, ≥ grade 2 acute GVHD, and cases requiring ≥ 2 immunosuppressive drugs for treating acute GVHD. In the comparison of survival outcomes according to conditioning regimen, the Bu/Flu group seemed to show better results than the Treo/Flu group (60% vs.46.2%, P = 0.092 for overall survival; 56.4% vs. 38.5%, P = 0.193 for relapse-free survival). In additional analysis for only HCT-CI high-risk groups, there was no difference in transplant outcomes except that the Treo/Flu group tended to have a higher NRM within one year after transplantation. Survival outcomes of both groups were similar. Conclusion This study suggests that Treo/Flu conditioning may be an alternative to Bu/Flu regimen in elderly patients with high-risk who are not suitable for standard conditioning.

Acute fracture-related infection (FRI) is a common and serious complication of fracture treatment. The clinical symptoms of the patient and the results of the serological, radiological, and histopathologi-cal examinations can be divided into ‘Confirmatory’ criteria and ‘Suggestive’ criteria, allowing for the diagnosis of FRI. Treatment principles can be broadly categorized into (1) the DAIR (Debridement, Antimicrobial therapy, Implant Retention) method and (2) the staged reconstruction method. The choice of treatment depends on factors such as the time elapsed after infection, stability of the internal fixation device, reduction status, host physiology, and virulence of the pathogens. Thorough surgical debridement and irrigation, ensuring stability at the fracture site, reconstruction of bone defects, and appropriate soft tissue coverage, along with antibiotic therapy, are essential to suppress or eradicate the infection. The restoration of limb function should be promoted through proper soft tissue coverage and bone union at the fracture site.

Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Background: A fourth dose of vaccination is known to help reduce the severity and mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The South Korean vaccination guidelines for the fourth dose do not include healthcare workers (HCWs) as priority candidates. We investigated the necessity of the fourth dose in South Korean HCWs based on an 8-month follow-up period after the third vaccination. Methods: Changes in the surrogate virus neutralization test (sVNT) inhibition (%) score were measured at one month, four months and eight months after the third vaccination. The sVNT values were analyzed between infected and uninfected groups, and their trajectories were compared. Results: A total of 43 HCWs were enrolled in this study. In total, 28 cases (65.1%) were confirmed to be infected with SARS-CoV-2 (presumed omicron variant), and all had mild symptoms. Meanwhile, 22 cases (78.6%) were infected within four months of the third dose (median, 97.5 days). Eight months after the third dose, the SARS-CoV-2 (presumed omicron variant)-infected group showed significantly higher sVNT inhibition than that in the uninfected group (91.3% vs. 30.7%; P < 0.001). The antibody response due to hybrid immunity, provided by a combination of infection and vaccination, was maintained at sufficient levels for more than four months. Conclusion For HCWs who had coronavirus disease 2019 infection after completing a third vaccination, a sufficient antibody response was maintained until eight months after the third dose. The recommendation of the fourth dose may not be prioritized in subjects with hybrid immunity.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Background: Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. Methods: Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. Results: A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study.Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicroninfected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. Conclusion Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination.Further studies are needed to understand the characteristics of immunogenicity in these populations.

Background: and Purpose The natural course of adult-onset moyamoya disease (MMD) is unknown, and there is no medical treatment that halts its progression. We hypothesized that progressive shrinkage of large intracranial arteries occurs in adult-onset MMD, and that cilostazol inhibits this process. Methods: Serial high-resolution magnetic resonance imaging (HR-MRI) was performed on 66 patients with MMD: 30 patients received cilostazol, 21 received other antiplatelets, and 15 received no antiplatelets or had poor compliance to them. Serial HR-MRI was performed (interval between MRI scans: 29.67±18.02 months, mean±SD), and changes in outer diameter, luminal stenosis, and vascular enhancement were measured. Factors affecting HR-MRI changes were evaluated, including vascular risk factors and the ring finger protein 213 gene variant. Results: The progression of stenosis to occlusion, recurrent ischemic stroke, and the development of new stenotic segments were observed in seven, seven, and three patients, respectively. Serial HR-MRI indicated that the degree of stenosis increased with negative remodeling (outer diameter shrinkage). Patients who received cilostazol presented significantly larger outer diameters and lower degrees of stenosis compared with other groups (p=0.005 and p=0.031, respectively). After adjusting for clinical and genetic factors, only cilostazol use was independently associated with negative remodeling (odds ratio=0.29, 95% confidence interval=0.10–0.84, p=0.023). While vascular enhancement was observed in most patients (61 patients), the progression of enhancement or the occurrence of new vascular enhancement was rarely observed on follow-up HR-MRI (6 and 1 patients, respectively). Conclusions Adult-onset MMD induces progressive shrinkage of large intracranial arteries, which cilostazol treatment may prevent. Further randomized clinical trials are warranted.

Background/Aims: This study aimed to investigate whether urinary angiotensinogen (UAGT) excretion was associated with elevated blood pressure in patients with chronic kidney disease (CKD) and to evaluate the relationship among blood pressure, intra-renal renin-angiotensin system (RAS) activity, and dietary sodium in patients with CKD. Methods: Participants from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD) were included. Of the total cohort of 2,238 individuals with CKD, we included 1,955 participants who underwent complete 24-hour urinary sodium (24-hour UNa) analysis. They were categorized into three groups according to three tertiles of their 24-hour UNa, reflecting daily salt intake. To measure intra-renal RAS activity, the UAGT excretion was assayed with an enzyme-linked immunosorbent assay. Results: Elevated 24-hour UNa levels, logarithm of UAGT-to-creatinine ratio (UAGT/Cr), increased waist-to-hip ratio, and decreased estimated glomerular filtration rate were the risk factors for increased systolic blood pressure. Systolic blood pressure showed a positive correlation with 24-hour UNa levels and logarithm of UAGT/Cr. Conclusions UAGT and urinary sodium excretion are independent determinants of systolic blood pressure in patients with CKD. These findings suggest that increased systolic blood pressure in CKD patients is associated with both increased dietary sodium levels and intra-renal RAS activity. The risk of elevated systolic blood pressure in the 3rd tertile of both the UAGT/Cr and 24-hour UNa groups was about 2.3 times higher than that in the reference group.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a reliable inflammatory marker. A recent study reported that elevated NLR is associated with adverse cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI). We investigated whether NLR at emergency room (ER) is associated with mechanical complications of STEMI undergoing primary percutaneous coronary intervention (PCI). Methods: A total of 744 patients with STEMI who underwent successful primary PCI from 2009 to 2018 were enrolled in this study. Total and differential leukocyte counts were measured at ER. The NLR was calculated as the ratio of neutrophil count to lymphocyte count. Patients were divided into tertiles according to NLR. Mechanical complications of STEMI were defined by STEMI combined with sudden cardiac arrest, stent thrombosis, pericardial effusion, post myocardial infarction (MI) pericarditis, and post MI ventricular septal rupture, free-wall rupture, left ventricular thrombus, and acute mitral regurgitation during hospitalization. Results: Patients in the high NLR group (> 4.90) had higher risk of mechanical complications of STEMI (P = 0.001) compared with those in the low and intermediate groups (13% vs. 13% vs. 23%). On multivariable analysis, NLR remained an independent predictor for mechanical complications of STEMI (RR = 1.947, 95% CI = 1.136–3.339, P= 0.015) along with symptom-to balloon time (P = 0.002) and left ventricular dysfunction (P < 0.001). Conclusion NLR at ER is an independent predictor of mechanical complications of STEMI undergoing primary PCI. STEMI patients with high NLR are at increased risk for complications during hospitalization, therefore, needs more intensive treatment after PCI.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a reliable inflammatory marker. A recent study reported that elevated NLR is associated with adverse cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI). We investigated whether NLR at emergency room (ER) is associated with mechanical complications of STEMI undergoing primary percutaneous coronary intervention (PCI). Methods: A total of 744 patients with STEMI who underwent successful primary PCI from 2009 to 2018 were enrolled in this study. Total and differential leukocyte counts were measured at ER. The NLR was calculated as the ratio of neutrophil count to lymphocyte count. Patients were divided into tertiles according to NLR. Mechanical complications of STEMI were defined by STEMI combined with sudden cardiac arrest, stent thrombosis, pericardial effusion, post myocardial infarction (MI) pericarditis, and post MI ventricular septal rupture, free-wall rupture, left ventricular thrombus, and acute mitral regurgitation during hospitalization. Results: Patients in the high NLR group (> 4.90) had higher risk of mechanical complications of STEMI (P = 0.001) compared with those in the low and intermediate groups (13% vs. 13% vs. 23%). On multivariable analysis, NLR remained an independent predictor for mechanical complications of STEMI (RR = 1.947, 95% CI = 1.136–3.339, P= 0.015) along with symptom-to balloon time (P = 0.002) and left ventricular dysfunction (P < 0.001). Conclusion NLR at ER is an independent predictor of mechanical complications of STEMI undergoing primary PCI. STEMI patients with high NLR are at increased risk for complications during hospitalization, therefore, needs more intensive treatment after PCI.