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: High-resolution chest computed tomography (CT) is a crucial assessment tool for diagnosing Birt-Hogg-Dubé (BHD) syndrome. This study aimed to analyze differences of lung cysts between BHD and other cystic lung diseases. Methods: From January 2020 to December 2022, patients with multiple lung cysts who underwent chest CT at Gangnam Severance Hospital were included. Results: Over a 3-year period (from January 2020 to December 2022), out of 52,823 patients who underwent a chest CT scan, 301 (0.6%) patients with multiple lung cysts were enrolled in this study. Of enrolled patients, 24 (8.0%) were diagnosed with BHD. In patients with BHD, 95.8% exhibited bilateral cysts, and 83.3% showed basal predominance. The cysts’ maximal diameter averaged 32.1 mm (interquartile range, 26.5 to 43.5). Additionally, 95.8% of patients with BHD had diverse cyst sizes and morphologies. Multivariate logistic regression analysis revealed that bilateral cysts (odds ratio [OR], 12.393; 95% confidence interval [CI], 1.613 to 274.682; p=0.038), basal predominance (OR, 8.511; 95% CI, 2.252 to 39.392; p=0.002), maximum diameter (OR, 1.053; 95% CI, 1.009 to 1.108; p=0.032), and diversity of morphology (OR, 19.513; 95% CI, 2.833 to 398.119; p=0.010) were significant factors associated with BHD diagnosis. A multivariate prediction model for BHD diagnosis demonstrated a sensitivity of 95.83%, a specificity of 81.22%, and an area under the receiver operating characteristic curve of 0.951 (95% CI, 0.914 to 0.987). Conclusion Distinguishing features of lung cysts from other cystic lung diseases include bilateral cysts, basal dominance, large size, and irregular shape.

Background: In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea. Methods: From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period. Results: Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia. Conclusion These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.

Background: Shortage of organ donors in the Republic of Korea has become a major problem. To address this, it has been questioned whether heart transplant (HTx) allocation should be modified to reduce priority of older patients. We aimed to evaluate post-HTx outcomes according to recipient age and specific pre-HTx conditions using a nationwide prospective cohort. Methods: We analyzed clinical characteristics of 628 patients from the Korean Organ Transplant Registry who received HTx from January 2015 to December 2020. Enrolled recipients were divided into three groups according to age. We also included comorbidities including ambulatory status. Non-ambulatory status was defined as pre-HTx support with either extracorporeal membrane oxygenation, continuous renal replacement therapy, or mechanical ventilation. Results: Of the 628 patients, 195 were < 50 years, 322 were 50–64 years and 111 were ≥ 65years at transplant. Four hundred nine (65.1%) were ambulatory and 219 (34.9%) were nonambulatory. Older recipients tended to have more comorbidities, ischemic cardiomyopathy, and received older donors. Post-HTx survival was significantly lower in older recipients (P = 0.025) and recipients with non-ambulatory status (P < 0.001). However, in contrast to non-ambulatory recipients who showed significant survival differences according to the recipient’s age (P = 0.004), ambulatory recipients showed comparable outcomes (P = 0.465). Conclusion Our results do not support use of age alone as an allocation criterion. Transplant candidate age in combination with some comorbidities such as non-ambulatory status may identify patients at a sufficiently elevated risk at which suitability of HTx should be reconsidered.

Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

Background: Circulating tumor DNA (ctDNA) is a potential biomarker in pancreatic ductal adenocarcinoma (PDAC). However, studies on residual ctDNA in patients post-chemotherapy are limited. We assessed the prognostic value of residual ctDNA in metastatic PDAC relative to that of carbohydrate antigen 19-9 (CA19-9). Methods: ctDNA analysis using a targeted next-generation sequencing panel was performed at baseline and during chemotherapy response evaluation in 53 patients. Progression-free survival (PFS) and overall survival (OS) were first evaluated based on ctDNA positivity at baseline. For further comparison, patients testing ctDNA-positive at baseline were subdivided based on residual ctDNA into ctDNA responders (no residual ctDNA post-chemotherapy) and ctDNA non-responders (residual ctDNA post-chemotherapy). Additional survival analysis was performed based on CA19-9 levels. Results: The baseline ctDNA detection rate was 56.6%. Although clinical outcomes tended to be poorer in patients with baseline ctDNA positivity than in those without, the differences were not significant. Residual ctDNA post-chemotherapy was associated with reduced PFS and OS. The prognosis of ctDNA responders was better than that of non-responders but did not significantly differ from that of ctDNA-negative individuals (no ctDNA both at baseline and during post-chemotherapy). Compared with ctDNA responses to che-motherapy, a ≥ 50% decrease in the CA19-9 level had less effect on both PFS and OSbased on hazard ratios and significance levels. ctDNA could be monitored in half of the patients whose baseline CA19-9 levels were within the reference range. Conclusions Residual ctDNA analysis post-chemotherapy is a promising approach for predicting the clinical outcomes of patients with metastatic PDAC.

Background: Understanding the virulence and pathogenicity of invasive nontyphoidal Salmonella (iNTS) in children may support timely treatment and enable closer monitoring of chronic infections. iNTS epidemiology in Asia remains inadequately described. We analyzed the genetic diversity and virulence genes associated with extra-intestinal invasion in Korean children. Methods: Salmonella isolates from children < 18 yrs of age diagnosed with moderate-tosevere salmonellosis between January 2019 and December 2021 were subjected to antibiotic susceptibility testing and whole-genome sequencing. Results: In total, 58 cases were included. We identified 20 serotypes, the most prevalent being Salmonella Enteritidis (N = 21), followed by Infantis (N = 6), I 4,[5],12:i:- (N = 5), and Bareilly (N = 5). Extra-intestinal invasion occurred in 12 (20.7%) cases involving Salmonella Oranienburg (2/2), Give (1/1), Javiana (1/1), Paratyphi B var. L(+) tartrate+ (1/1), Schwarzengrund (1/1), Singapore (1/1), Montevideo (1/2), Saintpaul (1/2), I 4:b:- (1/2), Infantis (1/6), and Enteritidis (1/21). While the numbers of total virulence genes and genes belonging to major virulence categories did not significantly differ between iNTS and noniNTS, several genetic factors, including Salmonella pathogenicity island (SPI)-1 (P = 0.039), SPI-2 (P = 0.020), SPI-5 (P = 0.014), SPI-13 (P = 0.010), cytolethal distending toxin-related genes (P = 1.4 × 10 –4 ), fepC (P = 0.021), and tcpC (P = 0.040) were more frequent in invasive isolates. Conclusions Salmonella Enteritidis-ST11 predominated in infections among Korean children, but invasive isolates were rare. Early detection of genetic factors associated with extra-intestinal invasion will be helpful for prompt and appropriate treatment.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks clinical biomarkers. Exosomes are extracellular vesicles that facilitate cell–cell communication by distributing macromolecules, such as small RNAs (smRNAs). We assessed the potential of exosome-derived small RNAs (Ex-smRNAs) as PDAC biomarkers. Methods: Peripheral blood was collected from 51 patients with PDAC and 15 control individuals. Exosomes were isolated using an aqueous two-phase system. Ex-smRNAs were analyzed using smRNA sequencing. smRNA-mediated target gene regulation was verified via The Cancer Genome Atlas analysis and in vitro transfection and wound-healing assays using PDAC organoids. Results: The total Ex-smRNA count was substantially reduced in patients with PDAC compared with that in control individuals. The levels of microRNAs (miRNAs) miR-125a-5p, miR-30e-5p, miR-16-2-3p, miR-98-5p, and the let-7 family were significantly suppressed, whereas that of miR-6731-5p was significantly elevated. Let-7c-5p and miR-98-5p were found to interact with the long non-coding RNA OLMALINC to regulate their common target genes, BACH1 and CCND1, thus controlling PDAC proliferation and migration. The expressions of CARS1-AS1 and miR-142-5p were upregulated in treatment-responsive patients.Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15–0.73; P = 0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61–1.01; P = 0.0581) were associated with improved overall survival. Conclusions We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.

Background: Pig red blood cells (RBCs) are rapidly eliminated when transfused into nonhuman primates (NHPs) because of immune reactions involving antibody binding and complement activation. We assessed the relationship between post-transfusion hemolysis and complement activation. Methods: RBCs for transfusion were prepared from wild-type (WT) and genetically modified pigs and NHPs. After the withdrawal of 25% of the blood volume, NHPs received transfusions of WT (N = 4), triple knockout (TKO, N = 8), and TKO pig RBCs expressing human CD55 and CD39 (TKO/hCD55.hCD39, N = 4). Additional groups received repeated xenotransfusions (ReXTf, N = 3), NHP RBC transfusions (N = 3), or a saline infusion (N = 4).Blood samples were collected at multiple time points to measure Hb and complement fragment (C3a, C4a, and factor Bb) levels and agglutination titers. Results: Hb levels were restored by transfusions but not by saline infusion. The degree of complement activation varied with the type of transfused RBCs, with significant increases in C3a and factor Bb levels immediately after xenotransfusions but not allotransfusions.These increases were particularly notable in ReXTf and negatively correlated with Hb levels on post-transfusion day 1 (ρ = –0.547 and –0.556; P = 0.0187 and 0.0165, respectively).In TKO/hCD55.hCD39 pig RBC transfusions, C3a and factor Bb peak levels were delayed until post-transfusion day 3, unlike in TKO pig RBC transfusions. Conclusions Post-transfusion complement activation varies depending on prior sensitization and genetic modifications in pig RBCs. Monitoring complement activation can provide insight into the survival and compatibility of transfused RBCs in NHPs.

Background: In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea. Methods: From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period. Results: Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia. Conclusion These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.