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Anbalcabtagene autoleucel (Anbal-cel) is a CD19-directed CAR T-cell therapy incorporating dual PD-1 and TIGIT knockdown to enhance antitumor function and durability. We report the results of a Phase 1/2 study in patients with relapsed or refractory large B-cell lymphoma (LBCL). In Phase 2, 79 patients received Anbal-cel, and efficacy was evaluated in 73 patients. The complete response (CR) and partial response (PR) rates were 67.1% and 8.2%, respectively. Median progression-free survival (PFS) was 6.04 months (95% CI, 4.34-16.46), and the 6-, 12-, and 18-month PFS rates were 50.9%, 41.1%, and 35.2%, respectively. Median overall survival (OS) was not reached, with 12- and 18-month OS rates of 66.6% and 57.3%. CAR T-cell expansion was significantly greater in responders than in non-responders (median Cmax: 20,403 vs. 8,580 copies/μg). Patients were categorized into long-term response (LR) group or non-LR group based on sustained CR at 6 months. Reduced PD-1 and TIGIT expression on CAR-positive T cells was observed in LR group. Most patients (97.5%) experienced grade ≥3 adverse events, most commonly neutropenia (93.7%), followed by thrombocytopenia (41.8%) and anemia (30.4%). Cytokine release syndrome and neurologic events occurred in 57.0% and 13.9% of patients, respectively. Grade 3 CRS occurred in 8.9% of patients, with no grade 4 events reported, and grade ≥3 neurologic events occurred in 3.8%. Serious infections occurred in 25.3% of patients, and grade 5 infection was reported in 3 patients. This trial was registered at Clinicaltrials.gov (NCT04836507).

Liver fibrosis remains an unmet medical need with limited therapeutic options and high translational failure. Conventional two-dimensional stellate cell cultures and cytokine-induced organoids poorly recapitulate in vivo pathology. Here, we establish a physiologically relevant liver fibrosis model by generating organoids directly from carbon tetrachloride (CCl₄)-injured fibrotic mouse liver tissue. These disease-derived organoids preserved key pathological hallmarks, including extracellular matrix remodeling and metabolic dysfunction, showing strong transcriptomic resemblance to fibrotic liver tissue. Using a two-tier screening pipeline, candidate natural products were first evaluated in hepatic stellate cells (in vitro) and subsequently validated in organoids (ex vivo) and murine fibrosis models (in vivo). Sargassum japonica (S. japonica) consistently demonstrated anti-fibrotic efficacy across all models, suppressing collagen deposition and α-SMA expression while restoring hepatic metabolic metabolism. RNA-sequencing revealed concordant downregulation of fibrosis-associated pathways and reactivation of detoxification and lipid metabolism genes, indicating dual mechanisms of action: inhibition of fibrogenesis and promotion of metabolic recovery. These findings highlight S. japonica as a promising anti-fibrotic candidate, and fibrotic liver-derived organoids as a predictive platform for drug discovery and validation. This integrated pipeline provides a translational bridge between in vitro assays and in vivo disease models, accelerating the identification of novel therapeutics for chronic liver disease.

Osteoarthritis (OA) is a leading cause of disability, yet its acute environmental triggers remain poorly understood despite rising healthcare demand in aging societies. Short-term exposure may aggravate established OA, but claims-based visit dates reflect healthcare utilization rather than confirmed symptom onset. We linked the Korean National Health Insurance Service-National Sample Cohort (2002-2019) with nationwide air pollution data to examine short-term associations between six ambient pollutants (PM10, PM2.5, NO2, SO2, O3, and CO) and OA-related hospital visits (ICD-10 M15-M19). Using a time-stratified case-crossover design, we assessed subgroup-specific susceptibility across demographic, socioeconomic, lifestyle, and clinical characteristics using linked health-screening data. Among 3,697,314 OA-related visits, all six pollutants were positively associated with visits per interquartile range (IQR) increment: 5.28% (95% CI, 5.02-5.54) for NO2, 2.88% (2.59-3.16) for CO, 1.36% (1.10-1.63) for SO2, 0.90% (0.73-1.07) for PM10, 0.76% (0.44-1.08) for O3, and 0.73% (0.47-1.00) for PM2.5. After correction for multiple comparisons, pollutant-specific effect modification was observed for sex, age, residential area, insurance type, smoking, alcohol use, physical activity, body mass index, and comorbidity burden. In two-pollutant and principal-component analyses, the NO2 association remained robust and the mixture components were positively associated with visits. These findings extend the health burden of air pollution to acute musculoskeletal morbidity in a lower-exposure East Asian setting where these effects remain policy-relevant. By resolving susceptibility across multiple individual-level domains rarely available in prior studies, our study provides evidence to inform targeted environmental health protection in aging populations.

Background: Revaccination against Japanese encephalitis virus (JEV) in adult hematopoietic stem cell transplantation (HSCT) recipients is not recommended because of insufficient data regarding its efficacy and immunogenicity. Therefore, we aimed to evaluate JEV seropositivity in adult HSCT recipients and explored the seroconversion rate in pediatric HSCT recipients after vaccination against JEV. Methods: This prospective study was conducted at the National Cancer Center, Goyang, Korea. Adult HSCT recipients (n = 103) were enrolled who visited the outpatient clinic. Additionally, pediatric recipients (< 19 years old; n = 11) who received JEV vaccination were enrolled. We collected serum samples from these participants and healthy healthcare workers (n = 50) for comparison. The JEV seropositivity rates and anti-JEV antibody titers were evaluated using the plaque reduction neutralization test. Results: The JEV seropositivity rates were significantly lower in adult HSCT recipients than in healthy healthcare workers (55% vs. 92%, P < 0.001). In addition, only one out of nine pediatric recipients tested seropositive before JEV vaccination. However, six out of seven were seropositive after two doses of vaccination. Furthermore, all three recipients who completed the three-dose vaccination schedule turned seropositive. No significant seropositivity-related factors were identified in the multivariate analysis. Conclusion: The low anti-JEV antibody seropositivity rate in Korean adult HSCT recipients indicates an increased vulnerability to this virus. Our findings provide a theoretical basis for the potential establishment of appropriate prevention strategies targeting this high-risk group.

Genomic profiling plays a central role in risk stratification and therapeutic decision-making in acute myeloid leukemia (AML), yet the clinical implications of population-specific genomic architectures remain incompletely defined. We conducted a prospective, multicenter study of 603 adults with newly diagnosed AML in Korea, integrating targeted sequencing of 83 recurrently mutated genes with comprehensive clinical annotation across treatment intensities, including allogeneic hematopoietic stem cell transplantation (allo-HSCT). For contextual comparison, genomic profiles were evaluated against the Beat AML cohort. The overall genomic landscape was broadly conserved, supporting shared core disease biology across populations. However, RUNX1::RUNX1T1, CEBPA, GATA2, KIT, and DDX41 mutations were more frequent in the Korean cohort, whereas FLT3 and NPM1 mutations were less common. These differences translated into a distinct distribution of European LeukemiaNet (ELN) 2022 risk categories, with implications for therapeutic stratification. Notably, most DDX41 alterations were germline (3.2%), highlighting the need for systematic germline evaluation with implications for genetic counseling and donor selection. Although unadjusted overall survival appeared longer in the Korean cohort, this difference was not significant after adjustment for key clinical variables. These findings indicate that population-specific genomic distributions reshape the clinical application of risk stratification and support population-aware precision medicine strategies in AML.

Idiopathic pulmonary fibrosis (IPF) is associated with lung cancer, but its clinical impact in patients with lung cancer remains unclear. We evaluated the prevalence of coexisting IPF and its association with mortality and healthcare utilization among patients with newly diagnosed lung cancer. Using the Korean National Health Insurance Service Health Screening Cohort, we identified 10,123 incident lung cancer cases between 2002 and 2019. Propensity score overlap weighting was applied to balance baseline characteristics, and treatment-adjusted models were used to examine whether associations persisted after accounting for treatment differences. IPF prevalence at lung cancer diagnosis was 0.593%. In treatment-adjusted models, IPF was associated with higher all-cause mortality (hazard ratio [HR] 1.72, 95% confidence interval [CI] 1.34–2.21) and lung cancer–related mortality (HR 1.78, 95% CI 1.38–2.31). IPF was also associated with increased respiratory-related hospitalization (HR 1.83), emergency room visits (HR 1.65), intensive care unit admissions (HR 4.41), and admission frequency (incidence rate ratio [IRR] 2.88), as well as fewer days alive and out of hospital. These findings suggest that coexisting IPF is associated with substantially increased mortality and respiratory healthcare burden in lung cancer.

Background Difficult-to-treat depression (DTD) in older adults is associated with high rates of disability, hospitalization, and mortality. As the effectiveness of once daily theta burst stimulation (TBS) has been demonstrated in older adults, we aimed to explore the feasibility and clinical effects of an accelerated bilateral TBS protocol. Methods This single arm, open-label trial enrolled outpatients aged 60 years and over with a current major depressive episode and nonresponse to at least one antidepressant. Participants received continuous TBS (600 pulses) to the right dorsolateral prefrontal cortex (DLFPC) followed by intermittent TBS (600 pulses) to the left DLPFC, 8 times daily for 5 consecutive days. The primary outcome measures were proportion of participants retained in the study and change in Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included rates of remission defined by MADRS ≤ 10, changes in measures of anxiety and suicidality, and measures of tolerability including number of serious adverse events. Results 79 participants enrolled in the study over a period of 2.5 years, 78 (67.7 ± 5.9 yrs, 75.6 % female) of whom received majority of TBS sessions. MADRS scores decreased a mean ( ± SD) 8.5 ± 6.7 points following treatment completion (F(2,154) = 61.6, p < 0.0001) and this improvement persisted 4 weeks later (p < 0.0001). The remission rate was 18% at treatment end and increased to 24 % 4 weeks later. Symptoms of anxiety (p < 0.01) and suicidal ideation (p = 0.03) also improved at treatment end. Treatment was well-tolerated and no serious adverse events were reported. Conclusions Accelerated TBS is feasible in older patients with DTD; its efficacy is comparable to once daily TBS; and it is well-tolerated. If these results are confirmed in a larger randomized trial, accelerated TBS may become a preferred treatment option for older depressed patients. Clinicaltrials.gov Identifier NCT05119699

Cancer‐associated fibroblasts (CAFs) contribute to immunosuppression in the ovarian cancer microenvironment, partly through upregulation of indoleamine 2,3‐dioxygenase 1 (IDO1). This study examined CAF‐mediated suppression of T‐cell function and the potential of IDO1 inhibition to reverse these effects. CAFs from high‐grade serous ovarian cancer (HGSOC) patients exhibited increased IDO1, COX2, and PD‐L1 expression upon interaction with activated T cells, along with elevated immunosuppressive cytokines. CAFs suppressed T‐cell proliferation and induced PD‐1 expression in CD4+ and CD8+ T cells, effects reversed by epacadostat. IDO1 inhibition enhanced T‐cell proliferation via AKT signaling, restored T‐cell cytotoxicity, and increased ovarian cancer cell apoptosis. These findings suggest that targeting IDO1 may help counteract CAF‐mediated immunosuppression and enhance antitumor immunity in HGSOC.

Background/Objectives: Cancer-associated fibroblasts (CAFs) play a pivotal role in the tumor microenvironment. We conducted an analysis using RNA sequencing to identify specific markers for CAFs compared to normal fibroblasts (NFs) in non-small-cell carcinoma (NSCLC). Methods: CAFs and NFs were isolated and cultured from tumor tissues (primary tumor or metastatic lymph nodes) and matched non-tumor tissues, respectively. Bulk RNA sequencing was conducted on isolated CAFs and normal fibroblast NFs. Differential expressions, gene set enrichment, and CAF subpopulation prediction analyses were performed. Results: During the study period, 27 CAFs and 12 NFs were isolated and cultured from tumor and non-tumor tissues in patients with treatment-naïve NSCLC. Among them, 22 CAFs and 11 NFs were included in the RNA sequencing analysis. The 22 CAF samples consisted of 12 adenocarcinomas and 10 squamous cell carcinomas (SqCC), with 16 samples from the lungs and 6 samples from the lymph nodes. Notably, COL11A1, GREM1, CD36, and GAS6 showed a higher expression in CAFs than in NFs, whereas TNC and CXCL2 were more abundantly expressed in NFs. CD36 levels were elevated in CAFs from lymph nodes (LN-CAFs) compared with those from lung specimens (Lung-CAFs) and NFs. COL11A1 levels in Lung-CAFs surpassed those in LN-CAFs and NFs. Both GREM1 and GAS6 showed a strong expression in Lung-CAFs and LN-CAFs relative to NFs. CAFs exhibited features of the myofibroblast CAF subpopulation, whereas NFs displayed traits of the antigen-presenting CAF subtype. In the co-culture model of CAFs and THP-1 cells, the knockdown of GREM1 or GAS6 in CAFs significantly decreased the M2 marker expression in macrophages. Conclusions In NSCLC, GREM1 and GAS6 can be valuable diagnostic targets for CAFs from primary tumors and metastatic sites; they warrant further study.

IMPORTANCE Electroconvulsive therapy (ECT) practice during the COVID-19 pandemic necessitated restriction of bag-valve mask (BVM) ventilation to minimize disease transmission through aerosolization. To reduce BVM use, many sites decreased doses of anesthesia agents, but the associations of such dose reduction with clinical and tolerability outcomes are unknown. OBJECTIVES To investigate the association of COVID-19 pandemic modifications in ECT, including reduction in anesthetic dosage and BVM use, with the rates of clinical complications and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included data from patients receiving an index course of ECT for any clinical indication treated with methohexital and succinylcholine between March 16, 2017, and March 15, 2023, at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada. Data analysis occurred from February to December 2024. EXPOSURE Participants were split into 2 cohorts: pre-COVID-19 (treated between March 2017 and March 2020) and COVID-19 (treated between June 2020 and March 2023). MAIN OUTCOMES AND MEASURES The primary outcomes were BVM use and rates of complications (specifically, aspiration, bradycardia, insufficient initial sedation dosage, postictal agitation [PIA], residual weakness, and prolonged seizures). Secondary outcomes were rates of response and cognitive impairment. Multivariable logistic regression was used to assess associations of COVID-19 pandemic modifications with outcomes. RESULTS A total of 616 individuals (median [IQR] age, 45.0 [31.0-59.0] years; 342 female [55.5%]) were included in the analysis, with 362 in the pre-COVID-19 group and 254 in the COVID-19 group. Demographic and clinical characteristics were similar. The COVID-19 group received lower median (IQR) methohexital dosages (0.82 [0.72-0.96] mg/kg vs 0.87 [0.78-1.00] mg/kg; P = .007) and succinylcholine (0.33 [0.27-0.39] mg/kg vs 0.53 [0.45-0.59] mg/kg; P < .001) than the pre-COVID-19 group. The COVID-19 group had higher odds of insufficient initial sedation dosage (odds ratio, 2.16, 95% CI, 1.09-4.38) and PIA (odds ratio, 2.81; 95% CI, 1.76-4.56), with no difference for other complications. BVM use was reduced from standard use to 13.8% (35 individuals) during COVID-19. Groups were similar in the rates of response (pre-COVID-19, 246 individuals [68.0%]; COVID-19, 181 individuals [71.3%]; P = .38) and cognitive impairment (pre-COVID-19, 75 individuals [20.7%]; COVID-19, 49 individuals [19.3%]; P = .66). CONCLUSIONS AND RELEVANCE In this retrospective cohort study, reduction of anesthesia agents was associated with reduced BVM use, with similar clinical outcomes and tolerability other than increased rates of insufficient initial sedation dosage and PIA, suggesting that management of PIA with this anesthesia dosing strategy warrants further investigation.

Background Late-life depression (LLD) is often accompanied by cognitive impairment, which may persist despite antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) is an efficacious treatment for depression, with potential benefits on cognitive functioning. However, research on cognitive effects is inconclusive, relatively sparse in LLD, and predominantly focused on group-level cognitive changes. This study aimed to explore individual-level cognitive changes following rTMS treatment in patients with LLD.Method Data were analyzed from 153 patients with LLD from the FOUR-D study (ClinicalTrials.gov identifier: NCT02998580) who received bilateral standard rTMS or theta burst stimulation (TBS) targeting the dorsolateral prefrontal cortex (DLPFC). Cognitive function was assessed pre- and post-treatment using measures of executive function, information processing speed, and learning and memory. Reliable change indices, adjusted for practice effects and test-retest reliability, were employed to evaluate individual-level cognitive changes. Chi-square tests examined if proportions of cognitive improvers differed from expected proportions.Results Cognitive performance from baseline to end of treatment remained stable for most patients. Reliably improved performance was observed in 0.0% to 20.0% of participants across cognitive measures, while worsened performance was observed in 0.0% to 2.7%. A small but significant proportion (20.0%) of participants showed improvement in verbal learning.Conclusions Bilateral standard rTMS or TBS of the DLPFC in LLD yielded no substantial cognitive enhancing effects, although a small proportion showed improved verbal learning after treatment. Importantly, both interventions were cognitively safe with relatively stable performance across time. Future research is needed to explore approaches to enhance the cognitive benefits of standard rTMS and TBS in patients with LLD.

Background: The Korean National Cancer Screening Program (NCSP) for gastric cancer requires economic evaluation due to the low sensitivity of upper gastrointestinal series (UGIs) and the associated low cancer survival rate. This study aimed to ascertain the most cost-effective strategy for the NCSP. Methods: The hypothetical target population of this study was aged 40 years or older, and no actual participants were involved. Markov simulation models were constructed for 25 strategies, combinations of 1) screening methods (UGIs or endoscopy vs. endoscopy-only), 2) screening intervals (one, two, or three-year), and 3) upper age limit of screening (69, 74, 79 years old, or "no limit"). Costs, utility, and other input parameters were extracted from various databases and previous studies. Cost-utility, sensitivity, and scenario analyses were conducted. Results: The endoscopy-only strategy with a three-year interval with an upper age limit of 69 was the most cost-effective strategy with an incremental cost-utility ratio of KRW 13,354,106 per quality-adjusted life years. According to the probabilistic sensitivity analysis, the uncertainty of the result was significantly small. Scenario analysis is showed that as the screening rate increased, the endoscopy-only strategy saved more costs compared to the current NCSP. Therefore, it is important to maintain a high screening rate when altering the NCSP strategy. Conclusion: Endoscopy-only screening was more cost-effective method than UGIs for the NCSP. Furthermore, a three-year interval with an upper-age limit of 69 years was the most cost-effective strategy. Efforts to improve cost-effective screening guidelines will support the efficient use of medical resources. Additionally, maintaining a higher screening rate may maximize the impact of the modification in strategy on cost-effectiveness.

Nanographene oxide (NGO) exhibits immunomodulatory activity and holds promise as a therapeutic agent for graft-versus-host disease (GVHD). In a xenogeneic GVHD mouse model, NGO administration improves survival and attenuates pathology with reduced weight loss and leukocyte engraftment, without sustained systemic toxicity. In GVHD patient-derived peripheral blood mononuclear cells (PBMCs), NGO treatment shifts T cell subsets toward immune homeostasis by increasing naïve T cells and decreasing effector memory T cells. Integrated transcriptomic analyses of PBMCs from GVHD patients and healthy donors reveal downregulation of pro-inflammatory and interferon-gamma-signal transducer and activator of transcription 1 (IFN-γ-STAT1)-associated genes, coinciding with the suppression of M1 macrophage signatures and induction of anti-inflammatory profiles. Mechanistically, NGO inhibits STAT1 activation and biases macrophages toward an anti-inflammatory state, independent of reactive oxygen species scavenging and lipopolysaccharide-myeloid differentiation primary response 88 (LPS-MyD88) signaling. To improve translational feasibility, NGO-primed macrophages (NGO-Mac) are generated, which produce higher levels of interleukin-10 (IL-10), inhibit helper T cell 1 (Th1) differentiation, and promote regulatory T cell (Treg) induction in an IL-10-dependent manner. In vivo, NGO-Mac therapy reduces M1 macrophage infiltration, increases Treg frequencies, and attenuates GVHD pathology. These findings highlight NGO and NGO-Mac as complementary immunotherapies, while further studies on safety, biodistribution, and feasibility are necessary for translation.