Background: This study aimed to identify the clinical characteristics of multidrug-resistant/ rifampicin-resistant tuberculosis (MDR/RR-TB) in the Republic of Korea. Methods: Data of notified people with tuberculosis between July 2018 and December 2021 were retrieved from the Korea Tuberculosis Cohort database. MDR/RR-TB was further categorized according to isoniazid susceptibility as follows: multidrug-resistant tuberculosis (MDR-TB), rifampicin-monoresistant tuberculosis (RMR-TB), and RR-TB if susceptibility to isoniazid was unknown. Multivariable logistic regression analysis was conducted to identify the factors associated with MDR/RR-TB. Results: Between 2018 and 2021, the proportion of MDR/RR-TB cases among all TB cases and TB cases with known drug susceptibility test results was 2.1% (502/24,447). The proportions of MDR/RR-TB and MDR-TB cases among TB cases with known drug susceptibility test results were 3.3% (502/15,071) and 1.9% (292/15,071), respectively. Among all cases of rifampicin resistance, 31.7% (159/502) were RMR-TB and 10.2% (51/502) were RR-TB. Multivariable logistic regression analyses revealed that younger age, foreigners, and prior tuberculosis history were significantly associated with MDR/ RR-TB. Conclusion Rapid identification of rifampicin resistance targeting the high-risk populations, such as younger generations, foreign-born individuals, and previously treated patients are necessary for patient-centered care.

Purpose: This study aimed to explore the effects of both the presence and size of posterior subependymal germinal matrix hemorrhage (PS-GMH), considered a mild form of hemorrhage, on the neurodevelopmental outcomes of extremely preterm infants. Methods: A retrospective analysis was conducted on 221 extremely preterm infants, assessing their initial and term-equivalent age (TEA) cranial ultrasound (cUS) examinations from 2016 to 2021. Infants were classified based on the presence and size (small/large) of PS-GMH. Neurodevelopmental outcomes at corrected ages of 18-24 months were analyzed in 135 infants. Results: PS-GMH was identified in 86.9% (192/221) of the infants, with 13.5% (26/192) exhibiting large PS-GMH. Among the 135 infants who were followed up, those with PS-GMH were found to have younger gestational ages (P<0.001) and a higher incidence of maternal chorioamnionitis (P=0.016) than those without PS-GMH. Significant differences were observed in the incidence of grade II intraventricular hemorrhage (IVH) on initial cUS (P=0.003) and ventriculomegaly at TEA cUS (P=0.026) across the groups with no PS-GMH, small PS-GMH, and large PS-GMH. The large PS-GMH group exhibited a higher occurrence of grade II IVH than the small PS-GMH group (P=0.006). However, ventriculomegaly incidence did not significantly vary with PS-GMH status. Neurodevelopmental outcomes were also not significantly different across PS-GMH statuses. The adjusted odds ratios for any neurodevelopmental impairment, compared to the no PS-GMH group, were 1.70 (95% confidence interval [CI], 0.40 to 7.26; P=0.471) for all PS-GMH, 1.61 (95% CI, 0.37 to 6.93; P=0.526) for small PS-GMH, and 3.84 (95% CI, 0.62 to 24.00; P=0.150) for large PS-GMH. Conclusion PS-GMH was frequently observed in extremely preterm infants; however, it did not independently predict adverse neurodevelopmental outcomes.

Purpose: This study compared the diagnostic performance of two attenuation imaging (ATI) modes—low-frequency (3 MHz) and high-frequency (4 MHz)—for assessing hepatic steatosis, with histopathological hepatic fat fraction (HFF) as the reference standard. Methods: This prospective single-center study enrolled participants with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) scheduled for liver biopsy or surgery between June 2023 and June 2024. Attenuation coefficient (AC) values were consecutively measured using low- and high-frequency ATI modes, while the skin-to-region of interest distance (SRD) was measured simultaneously. Spearman correlation analysis evaluated the relationships of AC with HFF and SRD, and linear regression identified factors affecting AC. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Results: In total, 119 participants (mean age, 37.2±12.0 years; 87 men) were included, with 73 (61.3%) diagnosed with MASLD. HFF ranged from 0% to 50%. The AC values in the lowfrequency mode were significantly higher than those in the high-frequency mode (0.61 vs. 0.54 dB/cm/MHz, P<0.001). HFF significantly influenced AC in both modes, whereas SRD affected AC only in the high-frequency mode (P<0.001). AC correlated positively with HFF in both modes (r_s≥0.514, P<0.001) and negatively with SRD in the high-frequency mode (r_s=-0.338, P<0.001). The AUROC for hepatic steatosis did not differ significantly between the two modes (0.751 vs. 0.771; P=0.609). Conclusion The low-frequency mode produced higher AC values than the high-frequency mode and demonstrated comparable diagnostic accuracy for assessing hepatic steatosis. Unlike the high-frequency mode, the low-frequency mode was not influenced by SRD.

Purpose: Chronic pelvic pain syndrome (CPPS) is a multifactorial condition that can significantly diminish quality of life. Although some patients have reported persistent pelvic pain after radical prostatectomy (RP), the prevalence and direct causal relationship between CPPS and RP remain unclear. This multicenter prospective study aimed to evaluate the efficacy of Urovaxom for improving CPPS symptoms. Materials and Methods: A total of 52 prostate cancer patients who underwent RP were enrolled and administered Urovaxom (60 mg/day) for 12 weeks. Changes in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), and inflammation markers (white blood cell [WBC], C-reactive protein [CRP]) were analyzed using the Wilcoxon signed-rank test. Results: After 12 weeks of treatment, the NIH-CPSI total score significantly decreased from 19 (interquartile range [IQR], 16–23) to 12.5 (IQR, 8.0–16.8) (p<0.001). The OABSS total score decreased from 8 (IQR, 4–11) to 5 (IQR, 3.0–7.8), and the IPSS total score decreased from 13.5 (IQR, 10.0–22.8) to 10.5 (IQR, 5.0–17.0) (p<0.001). WBC levels showed a slight increase (p=0.028), but the clinical relevance of this change is uncertain and warrants further investigation. CRP changes were not statistically significant (p=0.274). Conclusions Urovaxom demonstrated significant efficacy in improving CPPS symptoms, particularly pain and reduced quality of life, in patients following RP. These findings suggest Urovaxom as a potential therapeutic option for CPPS after management using RP.

Purpose: To develop a machine learning (ML) classifier for predicting post-induction hypotension (PIH) in non-cardiac surgeries. Materials and Methods: Preoperative data and early vital signs were obtained from 3669 cases in the VitalDB database, an opensource registry. PIH was defined as sustained mean arterial pressure (MAP) <65 mm Hg within 20 minutes since induction or from induction to incision. Six different ML algorithms were used to create binary classifiers to predict PIH. The primary outcome was the area under the receiver operating characteristic curve (AUROC) of ML classifiers. Results: A total of 2321 (63.3%) cases exhibited PIH. Among ML classifiers, the random forest regressor and extremely gradient boosting regressor showed the highest AUROC, both recording a value of 0.772. Excluding these models, the light gradient boosting machine regressor showed the second highest AUROC [0.769; 95% confidence interval (CI), 0.767–0.771], followed by the gradient boosting regressor (0.768; 95% CI, 0.763–0.772), AdaBoost regressor (0.752; 95% CI, 0.743–0.761), and automatic relevance determination regression (0.685; 95% CI, 0.669–0.701). The top three important features were mean diastolic blood pressure (DBP), minimum MAP, and minimum DBP from anesthetic induction to tracheal intubation, and these features were lower in cases with PIH (all p<0.001). Conclusion ML classifiers exhibited moderate performance in predicting PIH, and have the potential for real-time prediction.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Background: Long-term use of bisphosphonate is a risk factor for atypical femoral fractures (AFFs). Femoral bowing is known to be associated with AFFs. However, whether femoral bowing quickens the occurrence of AFF is unknown. The purpose of this study was to determine whether AFF occurs earlier in patients with severe femoral bowing than in those without severe bowing. Methods: One hundred and sixty-four patients (186 AFFs) from January 2006 to December 2022 were included in this study.According to severity of femoral bowing, patients were divided into 2 groups: severe bowing group (26 femurs) and minimal to moderate bowing group (160 femurs). Age, sex, and completeness and location of AFF were compared between the 2 groups. We compared the time of AFF occurrence after bisphosphonate therapy using cumulative percentage between the 2 groups. Results: Age and sex were similar between the 2 groups, while body mass index (BMI) was lower (22.5 ± 3.0 kg/m 2 vs. 24.5 ± 3.5 kg/m 2 , p = 0.003) in the severe bowing group. The duration of bisphosphonate use was shorter in the severe bowing group than in the minimal to moderate bowing group (3.3 ± 3.8 years vs. 5.0 ± 4.0 years, p = 0.048). In the severe bowing group, 85% of AFFs were diaphyseal in contrast to the 46% in the minimal to moderate bowing group (p < 0.001). Cumulative percentage plot of AFFs in the severe bowing group was left-shifted compared to the minimal to moderate bowing group. Conclusions At the time of AFF diagnosis, the severe bowing group exhibited shorter duration of bisphosphonate use, lower BMI, and a higher incidence of diaphyseal location. Shortening the duration of bisphosphonate therapy may be advisable in patients with severe femoral bowing.

Background: Limited data are available on the adverse effects of new-onset diabetes after transplantation (NODAT) in solid organ transplantation (TPL) other than kidney. This study aimed to identify the risk of complications associated with NODAT in recipients of kidney, liver, or heart TPL. Methods: Using the Korean National Health Insurance Service database, recipients of kidney, liver, or heart TPL between 2009 and 2015 were identified. The incidence of coronary artery disease (CAD), cerebrovascular accident (CVA), and malignancy was compared across groups with NODAT, pretransplant diabetes mellitus (DM), and without DM using Cox regression analysis. Results: A total of 9,632 kidney, liver, or heart TPL recipients were included. During the median follow-up of 5.9 years, NODAT independently increased the incidence of CAD (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.39 to 4.30) and overall mortality (HR, 1.48; 95% CI, 1.14 to 1.95) compared to the reference group even after adjustment for confounders; this was more prominent in kidney TPL than in liver TPL. The risk of CVA was significantly increased by pretransplant DM but not by NODAT in both kidney and liver TPL (HR, 2.47; 95% CI, 1.68 to 3.65; and HR, 3.18; 95% CI, 1.07 to 9.48, respectively). NODAT increased the risk of malignancy in the crude model, which lost its statistical significance after confounder adjustment. Conclusion NODAT independently increases the risk of CAD and mortality after TPL, which is more evident in kidney recipients. There was no additional increased risk of CVA or malignancy with NODAT in solid organ TPL.