As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Background: and Purpose The Treat Stroke to Target (TST) was a randomized clinical trial involving French and Korean patients demonstrating that a lower low-density lipoprotein cholesterol (LDL-C, <70 mg/dL) target group (LT) experienced fewer cerebro-cardiovascular events than a higher target (90–110 mg/dL) group (HT). However, whether these results can be applied to Asian patients with different ischemic stroke subtypes remains unclear. Methods: Patients from 14 South Korean centers were analyzed separately. Patients with ischemic stroke or transient ischemic attack with evidence of atherosclerosis were randomized into LT and HT groups. The primary endpoint was a composite of ischemic stroke, myocardial infarction, coronary or cerebral revascularization, and cardiovascular death. Results: Among 712 enrolled patients, the mean LDL-C level was 71.0 mg/dL in 357 LT patients and 86.1 mg/dL in 355 HT patients. The primary endpoint occurred in 24 (6.7%) of LT and in 31 (8.7%) of HT group patients (adjusted hazard ratio [HR]=0.78; 95% confidence interval [CI]=0.45–1.33, P=0.353). Cardiovascular events alone occurred significantly less frequently in the LT than in the HT group (HR 0.26, 95% CI 0.09–0.80, P=0.019), whereas there were no significant differences in ischemic stroke events (HR 1.12, 95% CI 0.60–2.10, P=0.712). The benefit of LT was less apparent in patients with small vessel disease and intracranial atherosclerosis than in those with extracranial atherosclerosis. Conclusion In contrast to the French TST, the outcomes in Korean patients were neutral. Although LT was more effective in preventing cardiovascular diseases, it was not so in stroke prevention, probably attributed to the differences in stroke subtypes. Further studies are needed to elucidate the efficacy of statins and appropriate LDL-C targets in Asian patients with stroke.

Background: The tibiofibular syndesmosis is essential for preserving the stability of the ankle. Acute syndesmotic injuries with evident or latent instability usually warrant surgical interventions. This cadaveric study examines and compares biomechanical characteristics between the following treatments for syndesmosis injuries: suture-button fixation plus syndesmotic repair and screw fixation. Methods: The lower extremities of 10 cadavers disarticulated at the knee joints were used, yielding 20 feet. Ten feet underwent surgery using the suture-button fixation with syndesmotic repair, while the remaining 10 feet underwent surgery using screw fixation. Before surgical treatment of syndesmosis injuries, each cadaveric lower limb underwent preliminary physiological cyclic loading, which was followed by a series of postfixation cyclic loading tests after the surgical procedure. Results: Our principal finding is that suture-button fixation with syndesmotic repair provided torsional strength comparable to that of screw fixation. The mean failure torque did not differ between the 2 groups, but the rotational stiffness was significantly lower in the suture-button fixation/augmentation group. Conclusions Suture-button fixation/augmentation facilitates flexible (physiological) syndesmosis movement and may be a useful alternative treatment for ankle syndesmosis injury.

The detrimental effects of hyperlipidemia on the healing of rotator cuff tears are well documented. The proposed underlying mechanisms for these effects include alterations in the extracellular matrix, inflammation, and oxidative stress, which hamper the reparative processes in the affected tendon tissues. Recent therapeutic strategies target these pathways, reflecting a growing body of research dedicated to mitigating these effects and promoting healing. This literature review aims to provide a comprehensive understanding of the pathophysiology underlying rotator cuff tears, examine the interplay between hyperlipidemia and rotator cuff tear healing, synthesize current knowledge on contributing biological mechanisms, and outline potential therapeutic interventions to optimize clinical management and treatment outcomes for patients.

Background: This study aimed to investigate changes after repeated subacromial drug injections in a rat model of normal rotator cuff. Methods: Thirty-nine male Sprague-Dawley rats were divided into groups 1 (no injection, n = 3), 2 (parecoxib, n = 18; 6 subgroups, n = 3 each; 0.5 mg/kg), and 3 (triamcinolone, n = 18; 6 subgroups, n = 3 each; 0.3 mg/kg). Groups 2 and 3 received subacromial injections 1–6 times once weekly for 6 weeks. The supraspinatus and infraspinatus tendons and muscles were used for biomechanical and histological evaluation. The subacromial bursa was used to analyze the prostaglandin E2 (PEG2) level. Results: In the biomechanical test, load-to-failure and ultimate stress decreased in groups 2 and 3 with repeated injections and the values were significantly lower in group 3 than in group 1 only at the sixth injection (p = 0.007 and p = 0.008, respectively). On the Bonar score, the cellularity, ground substance, and total score were significantly different among the 3 groups at the fifth and sixth injections (cellularity: p = 0.028 and p = 0.033, ground substance: p = 0.018 and p = 0.006, and total score: p = 0.029 and p = 0.027, respectively). The myocyte cross-sectional area of the infraspinatus muscle showed a significant difference among the 3 groups at the third and fourth injections (p = 0.031 and p = 0.020, respectively). The PEG2 level in the subacromial bursa was significantly different among the 3 groups at the third, fifth, and sixth injections (p = 0.019, p = 0.004, and p = 0.004, respectively). Conclusions In the rat model of normal rotator cuff, repeated local injections of the cyclooxygenase-2 inhibitor showed fewer negative effects on the biomechanical and histological properties of the normal tendon than triamcinolone.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

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: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.