Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Latent tuberculosis infection (LTBI) is characterized by immune responses to Mycobacterium tuberculosis antigens without clinical symptoms or evidence of active tuberculosis. Effective LTBI management is crucial for tuberculosis elimination, requiring accurate diagnosis and treatment. In South Korea, LTBI guidelines have been updated periodically, the latest being in 2024. This review discusses the recent changes in the Korean guideline for the diagnosis and treatment of LTBI in adults.

Background: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen. Methods: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. The study is registered with ClinicalTrials.gov (NCT04485156) Results: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups. Conclusion The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

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: 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: This study aimed to validate pivotal pre-test probability (PTP)-coronary artery disease (CAD) models (CAD consortium model and IJC-CAD model). Materials and Methods: Traditional PTP models-CAD consortium models: two traditional PTP models were used under the CAD consortium framework, namely CAD1 and CAD2. Machine learning (ML)-based PTP models: two ML-based PTP models were derived from CAD1 and CAD2, and used to enhance predictive capabilities [ML-CAD2 and ML-IJC (IJC-CAD)]. The primary endpoint was obstructive CAD. The performance evaluation of these PTP models was conducted using receiver-operating characteristic analysis. Results: The study included 238 participants, among whom 157 individuals (65.9% of the total sample) had CAD. The IJC-CAD model demonstrated the highest performance with an area under the curve (AUC) of 0.860 [95% confidence interval (CI): 0.812– 0.909]. Following this, the ML-CAD2 model exhibited an AUC of 0.814 (95% CI: 0.758–0.870), CAD1 showed an AUC of 0.767 (95% CI: 0.705–0.830), and CAD2 had an AUC of 0.785 (95% CI: 0.726–0.845). Each of the PTP models was adjusted to have a CAD score cutoff that classified cases with a sensitivity of over 95%. The respective cutoff values were as follows: CAD1 and CAD2 >12, MLCAD2 >0.380, and IJC-CAD >0.367. All PTP models achieved a CAD sensitivity of over 95%. Similar to the AUC performance, the accuracy of the PTP models was highest for IJC-CAD, reaching 80.3%. The accuracy of ML-CAD2 was 77.7%, while that for CAD1 and CAD2 was 74.8% and 75.2%, respectively. Conclusion ML-CAD2 and IJC-CAD showed superior performance compared to traditional existing models (CAD1 and CAD2)

Purpose: We investigated the clinical features, current negative-pressure wound therapy (NPWT) management strategies, and outcomes of pelvic-perineal soft tissue infection after open pelvic fractures. Materials and Methods: We analyzed the data of patients admitted to our trauma center with pelvic-perineal soft tissue after open pelvic fractures over a 7-year period. We investigated the injury severity score (ISS), medical costs, number of NPWTs, time required to reach definite wound coverage, complications, fracture classifications, transfusion requirements, interventions, length of stay (LOS) in hospital and intensive care unit (ICU), and prognosis. Results: Twenty patients with open pelvic fractures were treated with NPWT, and one patient who underwent NPWT died of pelvic sepsis during ICU treatment. The median LOS in hospital and medical costs were 98 [56–164] days and 106400 [65600–171100] USD, respectively. Patients treated with instillation NPWT (iNPWT, n=10) had a shorter NPWT duration (24 [13–39] vs. 46 [42–91] days, p=0.023), time to definite wound coverage (30 [21–43] vs. 49 [42–93] days, p=0.026), and hospital LOS (56 [43–72] vs. 158 [101–192] days, p=0.001), as well as lower medical costs (67800 [42500–102500] vs. 144200 [110400–236000] USD, p=0.009) compared to those treated with conventional NPWT. Conclusion NPWT is a feasible method for treating pelvic soft tissue infections in patients with open pelvic fractures. iNPWT can reduce the duration of NPWT, hospital LOS, and medical costs.

Purpose: Cognitive behavioral therapy (CBT) has long been recognized as an effective treatment for depression and suicidality.Virtual reality (VR) technology is widely used for cognitive training for conditions such as anxiety disorder and post-traumatic stress disorder, but little research has considered VR-based CBT for depressive symptoms and suicidality. We tested the effectiveness and safety of a VR-based CBT program for depressive disorders. Materials and Methods: We recruited 57 participants from May 2022 through February 2023 using online advertisements. This multi-center, assessor-blinded, randomized, controlled exploratory trial used two groups: VR treatment group and treat as usual (TAU) group. VR treatment group received a VR mental health training/education program. TAU group received standard pharmacotherapy. Assessments were conducted at baseline, immediately after the 6-week treatment period, and 4 weeks after the end of the treatment period in each group. Results: Depression scores decreased significantly over time in both VR treatment and TAU groups, with no differences between the two groups. The suicidality score decreased significantly only in VR group. No group differences were found in the remission or response rate for depression, perceived stress, or clinical severity. No adverse events or motion sickness occurred during the VR treatment program. Conclusion VR CBT treatment for major depressive disorder has the potential to be equivalent to the gold-standard pharmacotherapy in reducing depressive symptoms, suicidality, and related clinical symptoms, with no difference in improvement found in this study. Thus, VR-based CBT might be an effective alternative to pharmacotherapy for depressive disorders.

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.