Purpose: This study aimed to evaluate the prognosis of the not evaluated (NE) group by comparing it with the lost to follow-up (LTFU) group among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB). Materials and Methods: This was a retrospective longitudinal follow-up study using an integrated database constructed by data linkage of the three national databases. This database included 7226 cases of MDR/RR-TB notified between 2011 and 2017 in South Korea. Results: Among the 7226 MDR/RR-TB cases, 730 (10.1%) were classified as LTFU group, and 353 (4.9%) as NE group. When comparing NE group with LTFU group, there were no significant differences in the all-cause mortality rate (18.1% vs. 13.8%, p=0.065), median time to death [404 days (interquartile range, IQR 46–850) vs. 443 days (IQR 185–1157), p=0.140], and retreatment rate (26.9% vs.22.2%, p=0.090). After adjusting for potential confounders, the adjusted hazard ratio (aHR) for all-cause mortality (aHR 1.11; 95% confidence interval 0.80-1.53; p=0.531) in NE group was not significantly different than that in LTFU group. Among retreated cases, NE group had a higher treatment success rate (57.9% vs 43.8%, p=0.029) and a lower LTFU rate (11.6% vs 38.3%, p<0.001) compared to LTFU group. Conclusion NE group had an unfavorable outcome comparable to LTFU group, suggesting undetected cases of LTFU or deaths during the referral process. Establishing an efficient patient referral system would contribute to reducing the incidence of NE cases.

Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

Purpose: This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB). Methods: CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses. Results: Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not. Conclusion CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.

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: This study aimed to evaluate the prognosis of the not evaluated (NE) group by comparing it with the lost to follow-up (LTFU) group among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB). Materials and Methods: This was a retrospective longitudinal follow-up study using an integrated database constructed by data linkage of the three national databases. This database included 7226 cases of MDR/RR-TB notified between 2011 and 2017 in South Korea. Results: Among the 7226 MDR/RR-TB cases, 730 (10.1%) were classified as LTFU group, and 353 (4.9%) as NE group. When comparing NE group with LTFU group, there were no significant differences in the all-cause mortality rate (18.1% vs. 13.8%, p=0.065), median time to death [404 days (interquartile range, IQR 46–850) vs. 443 days (IQR 185–1157), p=0.140], and retreatment rate (26.9% vs.22.2%, p=0.090). After adjusting for potential confounders, the adjusted hazard ratio (aHR) for all-cause mortality (aHR 1.11; 95% confidence interval 0.80-1.53; p=0.531) in NE group was not significantly different than that in LTFU group. Among retreated cases, NE group had a higher treatment success rate (57.9% vs 43.8%, p=0.029) and a lower LTFU rate (11.6% vs 38.3%, p<0.001) compared to LTFU group. Conclusion NE group had an unfavorable outcome comparable to LTFU group, suggesting undetected cases of LTFU or deaths during the referral process. Establishing an efficient patient referral system would contribute to reducing the incidence of NE cases.

Purpose: Determining the extent of radical lymphadenectomy at clinical early stage is challenging. We aimed to investigate the appropriate extent of lymphadenectomy in clinical early-stage right colon cancer. Methods: Patients with clinical stage 0 or I right colon cancer who underwent curative surgery from January 2007 to December 2021 were included in this retrospective study. The extent of lymph node (LN) metastases based on the distribution of LN metastases (LND: LND1 pericolic nodes, LND2 intermediate nodes, LND3 apical nodes), along with the depth of submucosal (SM) invasion (classed into SM1–3), were analyzed. Results: Of the 348 patients, distribution across pathologic stages was as follows: 30 patients (8.6%) at stage 0, 207 (59.5%) at stage I, 52 (14.9%) at stage II, and 59 (17.0%) at stage III. In pT1 tumor patients, LN metastases varied by SM invasion depth: 3.6% in SM1 (all LND1), 5.1% in SM2 (all LND1), and 17.5% in SM3 (LND1 10%, LND2 5%, LND3 2.5%). For pT2, pT3, and pT4 stages, LN metastasis rates were 16.2% (LND1 11.3%, LND2 3.8%, LND3 1.3%), 39.7% (LND1 28.9%, LND2 8.4%, LND3 2.4%), and 50% (LND1 25%, LND2 25%), respectively. Tumor invasion depth and lymphovascular invasion were identified as significant risk factors for LN metastasis extending to LND2–3. Conclusion Complete mesocolic excision should be considered for right-sided colon cancer because tumor infiltration deeper than SM2 could metastasize to LND2 or further. If preoperative endoscopy confirms SM1 or SM2 invasion, D2 lymphadenectomy could be a limited surgical option.

Purpose: This study aimed to analyze whether the occurrence of complications increases if radiotherapy (RT) is administered after breast reconstructive surgery using implants. Methods: This retrospective study included 80 patients who underwent breast reconstruction using implants, of which 16 (20.0%) underwent RT. Most patients underwent conventional fractionated RT (n = 13), and hypofractionated RT was performed in 3 patients. Most patients (n = 51, 63.8%) underwent delayed reconstruction, which involved implant replacement after tissue expander insertion. Only 29 patients (36.3%) underwent immediate reconstruction simultaneously with breast cancer surgery. Results: The median postoperative follow-up was 39.9 months (range, 8.7–120.3 months). Complications occurred in 18 (22.5%); infectionecrosis (n = 8), leakage/rupture (n = 8), and capsular contracture (n = 2). Infectionecrosis is common in patients undergoing RT. Complications occurred in 4 patients (25.0%) who received RT and 14 (21.9%) who did not receive RT, and complications did not significantly increase with RT (P = 0.511). There was no overall difference in complications between the immediate (4 of 29) and delayed (14 of 51) reconstruction groups (P = 0.129). Nine patients underwent reoperation because of complications; 3 (18.8%) received RT and 6 (9.4%) did not receive RT. The reoperation rate did not increase significantly with RT (P = 0.254). There were 3 cases of recurrence, and patients who received RT had no recurrence. Conclusion RT did not significantly increase the complication or reoperation rates if reconstructive surgery was performed using implants. Therefore, RT should be performed in patients at a high risk of recurrence.

Parkinson’s disease (PD) is a movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have shown that necroptosis is involved in the development of inflammatory and neurodegenerative diseases. Receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) play key roles in necroptosis, with MLKL being the final executor of necroptosis. Necrosulfonamide (NSA) is a specific inhibitor of MLKL, and its therapeutic effects in various inflammatory and neurological disorders have been previously reported. However, its role in PD has not yet been clearly demonstrated. In this study, we examined the effects of NSA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. NSA reduced dopaminergic cell death and restored the expression of neurotrophic factors, such as BDNF, GDNF, and PGC-1α, in the SN region of MPTP mice. In addition, NSA inhibited microglial/ astrocyte activation and the expression of proinflammatory markers, such as iNOS, TNF-α, IL-1β, and IL-6. NSA also reduced oxidative stress markers, such as 8-OHdG and 4-HNE, while enhancing Nrf2-driven antioxidant enzymes, including HO-1, catalase, MnSOD, GCLC, and GCLM. We found that NSA inhibited MLKL phosphorylation in dopaminergic neurons and microglia, which may have reduced neuronal cell death and inflammation. Therefore, NSA-mediated suppression of dopaminergic neuronal cell death, inflammation, and oxidative stress may have therapeutic potential in PD.

Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties. This study investigated the protective effects of RVT against APAP-induced ALI in rats, and explored its influence on the pharmacokinetics of tofacitinib. In ALI rats, both intravenous and oral administration of tofacitinib resulted in a significant (207% and 181%) increase in the area under the plasma concentration-time curve (AUC), primarily driven by a substantial reduction (66.1%) in non-renal clearance (CLNR) compared to that in control (CON) rats. Notably, RVT administration in ALI rats provided effective liver protection, partially restoring liver function, as evidenced by normalized glutamate oxaloacetate transaminase levels and the pharmacokinetic parameters, AUC and CLNR, closer to those observed in untreated CON rats (117% and 81.9%, respectively). These findings highlight the importance of considering the potential interactions between RVT or polyphenol-rich natural products and medications in patients with ALI in clinical practice.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.