Background: In the era of nucleoside analogs (NA), we investigated the safety of using hepatitis B surface antigen (HBsAg)-positive grafts in liver transplantation (LT) using nationwide KOTRY data. Methods: Among 4,265 adult LTs in the KOTRY registry (April 2014–January 2020), 20 (0.5%) used HBsAg(+) grafts. The S(+) group was compared with HBsAg-nega-tive groups, both HBcAb(+) (C[+]) and HBcAb(−) (SC[−]), using 1:1 propensity scorematching. Patient and graft survival were evaluated using Kaplan–Meier analysis.Cox regression was used to identify prognostic factors. Results: No significant differences were observed in patient or graft survival be-tween S(+) and C(+) or SC(−) groups. Key prognostic factors for patient survivalincluded age, HCC, MELD score, ascites, and encephalopathy. For graft survival, HCC, preoperative HCC treatment, MELD score, ascites, and encephalopathy were significant. HBV recurrence occurred in the S(+) group, but did not compromise outcomes. Conclusion In HBV-endemic regions, HBsAg(+) liver grafts can be safely used to expand the donor pool without compromising LT outcomes when combined with appropriate prophylaxis.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Background: Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. Methods: A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. Results: Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. Conclusion The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

Objective: The role of low-density lipoprotein cholesterol (LDL-C) after carotid artery stenting (CAS) is not well known with respect to stented-territory infarction (STI) and instent restenosis (ISR). We hypothesized that LDL-C levels after CAS might be independently associated with STI and ISR. Methods: We conducted a retrospective study for patients with significant extracranial carotid stenosis who were subjected to CAS between September 2013 and May 2021. LDL-C levels were measured after 6 and 12 months following CAS. The association between STI and ISR, and LDL-C was explored using Cox proportional-hazard model. Results: Of 244 patients enrolled, STI and ISR were observed in 11 (4.5%) and 10 (4.1%) patients, respectively. In multivariable analysis, higher white blood cell count (hazard ratio [HR], 1.408 per 103 /mm3 ; 95% confidence interval [CI], 1.085–1.828; p=0.010), higher LDL-C levels after 12 months (HR, 1.037 per 1 mg/dL; 95% CI, 1.011–1.063; p=0.005), and ISR (HR, 13.526; 95% CI, 3.405–53.725; p<0.001) were independent predictors of STI. Diabetes (HR, 4.746; 95% CI, 1.026–21.948; p=0.046), smaller stent diameter (HR, 0.725 per 1 mm; 95% CI, 0.537–0.980; p=0.036), and higher LDL-C levels after 12 months (HR, 1.031 per 1 mg/dL; 95% CI, 1.007–1.055; p=0.011) were independent predictors of ISR. Conclusion We showed that LDL-C levels after 12 months independently predict STI and ISR after CAS. It is necessary to investigate the optimal target LDL-C level for STI prevention through well designed research in the future.

Purpose: Six forms relating to decisions on life-sustaining treatment (LST) for patients at the end-of-life (EOL) in hospital are required by the “Act on Decision of LST for Patients at the EOL.” We investigated the preparation and creation status of these documents from the database of the National Agency for Management of LST. Materials and Methods: We analyzed the contents and details of each document necessary for decisions on LST, and the creation status of forms. We defined patients completing form 1 as “self-determined” of LST, and those whose family members had completed form 11/12 as “family decision” of LST. According to the determination subject, we compared the four items of LST on form 13 (the paper of implementation of LST) and the documentation time interval between forms. Results: The six forms require information about the patient, doctor, specialized doctor, family members, institution, decision for LST, and intention to use hospice services. Of 44,381 who had completed at least one document, 36,693 patients had form 13. Among them, 11,531, 10,976, and 12,551 people completed forms 1, 11, and 12, respectively. The documentation time interval from forms 1, 11, or 12 to form 13 was 8.6±13.6 days, 1.0±9.5 days, and 1.5±9.7 days, respectively. Conclusion The self-determination rate of LST was 31% and the mean time interval from self-determination to implementation of LST was 8.6 days. The creation of these forms still takes place when the patients are close to death.

Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of ⁶⁸Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body ¹⁸F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. ⁶⁸Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient's serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.
Alkaline Phosphatase ; Biopsy, Large-Core Needle ; Diagnosis ; Drug Therapy ; Humans ; Hypophosphatemia ; Lymph Nodes ; Lymphoma ; Lymphoma, Follicular ; Middle Aged ; Osteomalacia ; Phosphorus ; Positron-Emission Tomography and Computed Tomography ; Vitamins

PURPOSE: To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. METHODS: To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. RESULTS: Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. CONCLUSIONS: This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.
Adult ; Animals ; Apoptosis ; Bone Marrow ; Cystitis ; Female ; Fibrosis ; Gene Expression ; Human Embryonic Stem Cells ; Humans ; Ketamine ; Mast Cells ; Mesenchymal Stromal Cells ; Multipotent Stem Cells ; Pelvic Pain ; Rats ; Urinary Bladder

Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of ⁶⁸Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body ¹⁸F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. ⁶⁸Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient's serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.

Extracellular vesicles (EVs) not only eliminate unwanted molecular components, but also carry molecular cargo essential for specific intercellular communication mechanisms. As the molecular characteristics and biogenetical mechanisms of heterogeneous EVs are different, many studies have attempted to purify and characterize EVs. In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. However, several unresolved issues and challenges remain despite these promising results, including source variability before the isolation of exosomes from body fluids, the contamination of proteins during isolation, and methodological issues related to the purification of exosomes. This paper reviews the general characteristics of EVs, particularly microvesicles and exosomes, along with their physiological roles and contribution to the pathogenesis of major diseases, several widely used methods to isolate exosomes, and challenges in the development of disease biomarkers using the molecular contents of EVs isolated from body fluids.
Biomarkers* ; Body Fluids ; Exosomes ; Extracellular Vesicles* ; Nucleic Acids

An esophagomediastinal fistula is rare complication of nontuberculous mycobacterium infection. Here, we report the case of a patient with advanced acquired immunodeficiency syndrome who presented with a fever, cough, and dyspnea, and was eventually diagnosed with nontuberculous mycobacterium infection. Computed tomography revealed multiple lymphadenopathy with an esophagomediastinal fistula. The patient was treated with anti-mycobacterial medications and endoscopic fistula closure.
Acquired Immunodeficiency Syndrome ; Cough ; Dyspnea ; Esophageal Fistula ; Fever ; Fistula* ; HIV* ; Humans ; Lymphatic Diseases ; Mycobacterium Infections, Nontuberculous*