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: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

Background: Genetic neuromuscular diseases (NMDs) are a heterogeneous group of conditions that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study was performed to identify pathogenic or likely pathogenic variants (PLPVs), calculate carrier frequencies, and predict the genetic prevalence of autosomal recessive-NMDs (AR-NMDs) in a Korean population. Methods: In total, 267 genes were associated with AR-NMDs. We analyzed genetic variants from 984 Korean whole genomes and identified PLPVs to assess the carrier frequency and genetic prevalence of the variants. Results: We identified 165 PLPVs, including 75 literature verified and 90 manually verified variants. Most PLPVs in AR-NMD genes were frameshifts (61, 37.0%), followed by nonsense (36, 21.8%), missense (35, 21.2%), and splice variants (28, 17.0%). The carrier frequency of the AR-NMDs was 27.1%. DYSF exhibited the highest carrier frequency (1.63%), followed by GAA (1.55%), HEXB (1.53%), PREPL (0.76%), NEB (0.66%), ADSS1 (0.65%), ALPK3 (0.65%), and CHRNG (0.65%). The predicted genetic prevalence of AR-NMDs in the Korean population was 38.0 cases per 100,000 individuals. DYSF (6.7 cases per 100,000 individuals) showed the highest genetic prevalence. The variant with the highest allele frequency was c.1250C>T in HEXB at 0.00764, followed by c.[752T>C; c.761C>T] in GAA at 0.00505, and c.2055+2T>G in DYSF at 0.00437. Conclusion Our study suggests that 27.1% of the Korean population are healthy carriers of at least one AR-NMD causing PLPV, revealing the genetic prevalence of NMDs in the Korean population.

Objective: : To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation. Methods: : This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns—classified as local, diffuse, distant, or multifocal—and time to recurrence were compared between patients with and without VO. Results: : The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7–38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35). Conclusion : Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other central nervous tumors such as meningiomas and spinal ependymomas. Symptoms vary according to the age at diagnosis and the location of these tumors. The diagnostic criteria of NF2 have been regularly revised and recently updated in 2022 with a new nomenclature “NF2-related schwannomatosis” to differentiate NF2 from other schwannoma predisposing disorders, such as SMARCB1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1)-, LZTR1 (leucine zipper-like transcription regulator 1)-, and 22q-related schwannomatosis. Addition to the clinical features, genetic testing for pathogenic variants in these genes became an important essence to support diagnosis of NF2 and other schwannomatosis, including mosaic conditions.

Purpose: Obesity refers to a condition in which there is excessive fat in the body and is caused by an imbalanced diet and a decrease in physical activity. Accordingly, regular exercise is reported to help improve and prevent obesity. Therefore, this study investigated the effects of short-term resistance training (RT) on weight loss, lipid profiles, blood pressure, atherogenic indices, and inflammation in middle-aged mice. Methods: Adult mice (7.5-month-old) were randomly divided into three groups comprising 7 mice per group: a normal diet group (NDC); a high-fat diet group (HDC, 45% total calories as fat); and a high-fat diet plus resistance training group (HDRT). The mice in the resistance training group performed climbing exercises using a ladder for the experimental period of 5 days/week for 4 weeks. The indicated intensity load was adjusted by individual % of animal body weight. The load gradually increased every week, and a total of 4 repetitions/set and 3 sets/day with 1 minute of rest provided between sets were performed. After sacrifice, analysis of serum and mRNA expression in the tissues were performed. Results: The HDC group showed a significant increase in systolic blood pressure (SBP) compared to the NDC group, while the HDRT group had a lower SBP relative to the HDC group. RT significantly improved blood lipid levels (triglycerides [TG], low-density lipoprotein [LDL], non-high-density lipoprotein [nonHDL], and very-low-density lipoprotein cholesterol [VLDL-C]). Arteriosclerosis improved through resistance training as observed in the changes in the arteriosclerosis indices (atherogenic index of plasma [AIP], Castelli risk index [CRI]-I, CRI-II, and atherogenic coefficient [AC]). In addition, the HDRT group showed decreased mRNA expression levels of tumor necrosis factor-alpha (Tnfa), interleukin-1 beta (Il-1b), and Il-6 in muscle tissue when compared with the HDC. Conclusion This study confirmed that RT improves blood lipids and inflammation profiles, regulates blood pressure, and improves atherosclerosis in obese mice.

Background: To identify the optimal surgical technique for single-level anterior cervical discectomy and fusion (ACDF), this study compared surgical outcomes and incidence of adjacent segment degeneration (ASD) in patients undergoing single-level ACDF using cage alone single-level fusion and plate fixation techniques. Methods: This single-center retrospective study (2003–2018) included patients who underwent single-level ACDF with either plate fixation (PLATE) or cage (CAGE) alone. The radiologic and clinical outcomes between the 2 surgical groups were compared over a 4-year follow-up period. Outcomes of interest included parameters related to range of motion, sagittal alignment, as well as fusion, subsidence, and ASD rates. Clinical outcomes were evaluated using the Neck Disability Index (NDI) and visual analog scale (VAS) for pain. Dysphagia and hoarseness rates were estimated based on medical records. Results: Forty-seven patients were included (n=17 in CAGE group). In the CAGE group, 94.1% of the patients had Bridwell grade 1 or 2, compared to 83.3% in the PLATE group (p = 0.396). Subsidence occurred in 12.5% and 3.6% of the CAGE and PLATE cases, respectively (p = 0.543). Segmental kyphosis progressed in the CAGE group compared to the PLATE group at 12, 24, and 48 months (p < 0.001). Radiographic ASD was observed in 41.2% and 30.0% of patients in the CAGE and PLATE groups, respectively, with a higher incidence in the upper segments for both groups. Preoperative NDI scores were similar between the groups; however, postoperatively, the CAGE group had significantly lower NDI scores (3.50 ± 2.74 vs. 8.00 ± 5.81) at 4 years (p = 0.020). Neck pain VAS scores also showed significant improvement in the CAGE group (2.33 ± 2.94) compared with that in the PLATE group (3.07 ± 2.31) at 4 years (p = 0.045). Both groups showed comparable arm pain VAS scores at 2 and 4 years postoperatively. Postoperative dysphagia occurred in 1 patient in the PLATE group, resolving almost completely by 1 year. Conclusions Single-level ACDF using a cage alone technique demonstrated favorable radiologic and clinical outcomes overall compared to plate-augmented ACDF. However, plate augmentation is recommended for patients with severe cervical kyphosis or those at high risk of subsidence.

Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.

Background/Aims: Inflammatory bowel disease (IBD) affects health-related quality of life (HRQoL). The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score is strongly correlated with HRQoL in IBD patients. This study aimed to assess the factors influencing HRQoL in IBD patients. Methods: In this prospective study, all patients with ulcerative colitis (UC) and Crohn’s disease (CD) completed the SIBDQ at enrollment; some patients also completed a second SIBDQ at follow-up. Multiple linear regression analysis was used to determine associations between SIBDQ scores and clinical factors. Results: A total of 1,020 patients participated (UC, 67%; CD, 33%). The median SIBDQ score was 52 (interquartile range, 44 to 59). In UC patients, the stool frequency (β=–2.333, p<0.001), Physician Global Assessment score (β=–3.950, p<0.001), fecal calprotectin level (β=–4.014, p<0.001), and corticosteroid use (β=–4.809, p=0.006) were negatively correlated with the SIBDQ score. In CD patients, the number of diarrhea episodes per day (β=–1.467, p=0.024) and Crohn's Disease Activity Index score (β=–0.045, p<0.001) were negatively correlated with the SIBDQ score. A total of 202 patients completed the second SIBDQ within a mean of 3.4 years. The distributions of SIBDQ score changes were as follows: decrease >10%, 28%; –10%10%, 43%. In both the initial SIBDQ and follow-up SIBDQ, scores for items pertaining to systemic symptoms (tension and fatigue) were relatively low. Conclusions Bowel movement-related problems significantly affect the HRQoL of both UC and CD patients. IBD patients scored lower on SIBDQ items related to general well-being. After 3 years of follow-up at the IBD clinic, 43% of patients showed a significant improvement in HRQoL.