Background/Aims: To analyze the characteristics of the sputum microbiota of patients with nontuberculous mycobacteria pulmonary disease (NTM-PD) based on treatment status. Methods: Twenty-eight sputum samples from 14 patients with NTM-PD, including 14 samples from the microbiologically cured group (7 at baseline and 7 during follow-up) and 14 from the treatment-refractory group (7 at baseline and 7 during follow-up) were included in this study. Bacterial microbiota was analyzed by sequencing the V3–V4 region of the 16S rRNA gene. Results: Among the 14 patients, most had infections with Mycobacterium avium complex (n = 6), followed by Mycobacterium abscessus (n = 5); three patients exhibited mixed infection with both organisms. Alpha-diversity was higher in the cured group than in the treatment refractory group in both the baseline sputum (ACE, p = 0.005; Chao1, p = 0.010; Jackknife, p = 0.022, 0.043; Shannon, p = 0.048) and follow-up sputum (ACE, p = 0.018). Linear discriminant analysis effect size revealed that several taxa showed differential distributions based on treatment status. At the species level, Streptococcus pneumoniae, Prevotella melaninogenica, Haemophilus parahaemolyticus, Haemophilus haemolyticus, Fusobacterium nucleatum, Neisseria elongata, and Prevotella denticola were more abundant in sputum from the microbiologically cured group than in that from the refractory group (all p < 0.05). Conclusions In contrast to patients with treatment-refractory NTM-PD, those with stable disease without recurrence had higher microbial diversity in their sputum, including several predominant taxa.

Background: Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods. Methods: A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2. Results: All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%). Conclusions Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection commonly observed in immunocompromised patients, necessitating prompt diagnosis and treatment. This review evaluates the diagnostic performance of various tests used for PJP diagnosis through a comprehensive literature review. Additionally, we propose a diagnostic algorithm tailored to non-human immunodeficiency virus immunocompromised patients, considering the specific characteristics of current medical resources in Korea.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.

Background/Aims: To analyze the characteristics of the sputum microbiota of patients with nontuberculous mycobacteria pulmonary disease (NTM-PD) based on treatment status. Methods: Twenty-eight sputum samples from 14 patients with NTM-PD, including 14 samples from the microbiologically cured group (7 at baseline and 7 during follow-up) and 14 from the treatment-refractory group (7 at baseline and 7 during follow-up) were included in this study. Bacterial microbiota was analyzed by sequencing the V3–V4 region of the 16S rRNA gene. Results: Among the 14 patients, most had infections with Mycobacterium avium complex (n = 6), followed by Mycobacterium abscessus (n = 5); three patients exhibited mixed infection with both organisms. Alpha-diversity was higher in the cured group than in the treatment refractory group in both the baseline sputum (ACE, p = 0.005; Chao1, p = 0.010; Jackknife, p = 0.022, 0.043; Shannon, p = 0.048) and follow-up sputum (ACE, p = 0.018). Linear discriminant analysis effect size revealed that several taxa showed differential distributions based on treatment status. At the species level, Streptococcus pneumoniae, Prevotella melaninogenica, Haemophilus parahaemolyticus, Haemophilus haemolyticus, Fusobacterium nucleatum, Neisseria elongata, and Prevotella denticola were more abundant in sputum from the microbiologically cured group than in that from the refractory group (all p < 0.05). Conclusions In contrast to patients with treatment-refractory NTM-PD, those with stable disease without recurrence had higher microbial diversity in their sputum, including several predominant taxa.

Background/Aims: To analyze the characteristics of the sputum microbiota of patients with nontuberculous mycobacteria pulmonary disease (NTM-PD) based on treatment status. Methods: Twenty-eight sputum samples from 14 patients with NTM-PD, including 14 samples from the microbiologically cured group (7 at baseline and 7 during follow-up) and 14 from the treatment-refractory group (7 at baseline and 7 during follow-up) were included in this study. Bacterial microbiota was analyzed by sequencing the V3–V4 region of the 16S rRNA gene. Results: Among the 14 patients, most had infections with Mycobacterium avium complex (n = 6), followed by Mycobacterium abscessus (n = 5); three patients exhibited mixed infection with both organisms. Alpha-diversity was higher in the cured group than in the treatment refractory group in both the baseline sputum (ACE, p = 0.005; Chao1, p = 0.010; Jackknife, p = 0.022, 0.043; Shannon, p = 0.048) and follow-up sputum (ACE, p = 0.018). Linear discriminant analysis effect size revealed that several taxa showed differential distributions based on treatment status. At the species level, Streptococcus pneumoniae, Prevotella melaninogenica, Haemophilus parahaemolyticus, Haemophilus haemolyticus, Fusobacterium nucleatum, Neisseria elongata, and Prevotella denticola were more abundant in sputum from the microbiologically cured group than in that from the refractory group (all p < 0.05). Conclusions In contrast to patients with treatment-refractory NTM-PD, those with stable disease without recurrence had higher microbial diversity in their sputum, including several predominant taxa.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.