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.

Background/Aims: Multiple myeloma (MM) predominantly affects elderly individuals, but studies on older patients with MM are limited. The clinical characteristics and survival outcomes of patients with MM aged 80 years or over were retrospectively analyzed. Methods: This retrospective multicenter study was conducted to investigate the clinical characteristics, treatment patterns, and survival outcomes of patients aged 80 years or over who were newly diagnosed with MM at five academic hospitals in Daegu, Korea, between 2010 and 2019. Results: A total of 127 patients with a median age of 83 years (range, 80–93 yr) were enrolled: 52 (40.9%) with Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, 84 (66.1%) with International Staging System (ISS) stage III disease, and 93 (73.2%) with a Charlson comorbidity index (CCI) > 4. Chemotherapy was administered to 86 patients (67.7%). The median overall survival was 9.3 months. Overall survival was significantly associated with ECOG PS > 2 (HR 2.26, 95% CI 1.43–3.59), ISS stage III (HR 1.99, 95% CI 1.18–3.34), and chemotherapy (HR 0.34, 95% CI 0.21–0.55). There was no statistically significant difference in event-free survival according to the type of anti-myeloma chemotherapy administered. The early mortality (EM) rate was 28.3%. Conclusions Even in patients with MM aged 80 years or over, chemotherapy can result in better survival outcomes than supportive care. Patients aged ≥ 80 years should not be excluded from chemotherapy based on age alone. However, reducing EM in elderly patients with newly diagnosed MM remains challenging.

Background: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen. Methods: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. The study is registered with ClinicalTrials.gov (NCT04485156) Results: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups. Conclusion The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Background and Objectives: The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men. Methods: COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups. Conclusions In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Background and Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism. Methods: New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12). Results: YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes. Conclusions YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.

This article presents two cases of extrahepatic portal vein anomalies that can be challenging during lymph node (LN) dissection in gastric cancer surgery. The first case was a participant for a clinical trial assessing the completeness of D2 LN dissection. The trial utilized near-infrared (NIR) lymphangiography with indocyanine green only after completing dissection of a certain topological LN station to detect any residual lymphatic tissue. However, the patient was excluded from the trial due to an unexpected extrahepatic portal vein confluence anomaly and aberrant common hepatic artery. Consequently, continuous lymphatic navigation with NIR imaging was utilized for remaining surgery. The second case featured a patient with an anteriorly positioned splenic vein, hindering LN dissection along the left gastric artery. Preoperative identification of great vessel anomalies around the stomach is critical to prevent life-threatening complications during LN dissection in gastric cancer surgery. Augmented imaging technology can be a valuable tool in ensuring oncologic safety and precision.

Background and Objectives: Certain medications are associated with ototoxicity. This study assesses drug-induced ototoxicity in South Korea by analyzing the Korean national health data. Subjects and Methods: Hospital records of National Health Insurance members from 2009 to 2016 were reviewed. Data were compared between patients with and without hearing loss (HL). Individuals with HL were identified as having a primary diagnosis code for sensorineural HL or another type of HL in at least one outpatient or inpatient record according to the International Classification of Diseases-10. Results: The members in the HL group increased slightly from 0.8% to 1.0% relative to the total sample, compared with 99.2% to 99.0% among the controls. The proportion of males in the HL group ranged from 45.6% to 47.6%, compared with 48.4% to 48.8% among the controls. The proportion of those aged ≥65 years in the HL group increased from 34.1% to 41.4%, compared with 10.6% to 13.3% among the controls. Hypertension prevalence (24.7%-25.7%) in the HL group was higher than that in the control group (12%-12.6%). Diabetes prevalence in the HL group was 10.6%-12.3%, compared with 4.4%-5.9% among the controls. The use of proton pump inhibitor components increased, particularly esomeprazole magnesium trihydrate and rabeprazole sodium, whereas the usage of pantoprazole sodium sesquihydrate and revaprazan was high initially but declined subsequently. The usage of painkillers such as acetaminophen, loxoprofen sodium, and ibuprofen remained high, and antibiotics such as cephalosporins indicated the highest usage. However, the use of penicillin antibiotics such as amoxicillin decreased significantly. Anticancer agents showed relatively low usage compared with other drug categories, whereas antihistamines showed extremely high usage across all years, with a continual increase. Conclusions These correlations and the underlying mechanisms necessitate further investigation, as several medicines have been linked to an increased risk of HL.