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Safety Evaluation of SH003 and Docetaxel Combination in Patients With Breast and Lung Cancer: A Multi-Center, Open-Label, Dose Escalation Phase I Clinical Trial
No full textBACKGROUND: Cancer remains one of the leading causes of death worldwide, underscoring the need for novel therapies. SH003, an herbal mixture composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, is a traditional Korean medicine formulation with potential to enhance chemotherapy efficacy and reduce toxicity. This study aimed to assess the safety and determine maximum tolerated dose of SH003 in combination with docetaxel in patients with advanced solid tumors, specifically lung and breast cancer. METHODS: This Phase I, multi-center, open-label, dose-escalation study enrolled patients with advanced lung or breast cancer. Participants received SH003 orally at doses of 2400, 3600, or 4800 mg daily, alongside intravenous docetaxel (75 mg/m(2)) every 21 days. A 3 + 3 dose-escalation design was employed to determine the maximum tolerated dose. Safety assessments and adverse event monitoring were conducted at each treatment cycle. RESULTS: Twelve participants were enrolled. SH003 was well tolerated up to 4800 mg/day, with no dose-limiting toxicities attributed to SH003. The most common adverse events were neutropenia, primarily associated with docetaxel, and mild dermatologic reactions such as eczema, rash acneiform, and pruritus. Preliminary evidence of disease stabilization was observed in several participants. CONCLUSION: The combination of SH003 and docetaxel demonstrated a favorable safety profile, with 4800 mg/day identified as maximum tolerated dose for SH003. These findings support further investigation in Phase II trials to assess therapeutic efficacy.Trial Registration: Clinical Research Information Service (https://cris.nih.go.kr) KCT0004770
Distinct gut microbiota profiles and network properties in older Korean individuals with subjective cognitive decline, mild cognitive impairment, and Alzheimer’s disease
No full textBACKGROUND: The gut microbiota may influence cognitive function via the gut-brain axis. This study aimed to investigate the gut microbiota profiles of 346 older Korean individuals with subjective cognitive decline but no symptoms (SCD), mild cognitive impairment (MCI), or Alzheimer's disease (AD). METHODS: Participants aged an average of 72.3 years underwent the profiling of cognitive function, amyloid-beta (Abeta) deposition, apolipoprotein E (APOE) genetic variants, depression status, nutrition, and lifestyles. Human fecal bacterial FASTA/Q data (SCD, n = 24; MCI, n = 246; AD, n = 76) were processed using Quantitative Insights Into Microbial Ecology 2 (QIIME2) tools. Operational taxonomic units (OTUs) and their counts were assigned with the National Center for Biotechnology Information Basic Local Alignment Search Tool (BLAST). Machine learning models (random forest and XGBoost) identified key bacterial taxa differentiating groups. RESULTS: Redundancy analysis revealed associations between gut microbiota composition and cognitive function, age, gender, nutritional status, and body mass index. All three groups shared 71 common bacterial genera with distinct taxonomic profiles across cognitive states. The AD group uniquely harbored Hominisplanchenecus and Lentihominibacter, while the SCD group exclusively contained Anaerosacchariphilus and Anaerobutyricum. Phascolarctobacterium was shared between the AD and MCI groups, and Anaerostipes between the MCI and SCD groups. The SCD group showed significantly elevated Bifidobacterium catenulatum, Anaerobutyricum hallii, and Anaerostipes hadrus. Network analysis demonstrated greater microbial community complexity in the SCD group compared to the MCI and AD groups. Gut bacteria correlated with depression, Abeta deposition, APOE status, and cognitive scores. CONCLUSIONS: This study identified distinct gut microbiota profiles associated with different stages of cognitive impairment in older Korean adults. The observed associations between gut bacterial composition and cognitive function, neurodegeneration biomarkers, and related clinical factors suggest potential relationships that warrant further investigation. These findings contribute to the growing understanding of gut-brain interactions in cognitive aging
Learning curve of a novice foot and ankle surgeon in minimally invasive calcaneal fracture surgery via the sinus tarsi approach
No full textThe sinus tarsi approach has gained popularity for treating calcaneal fractures; however, limited research exists on the learning curve among novice orthopedic surgeons. This study aimed to assess the learning curve of junior orthopedic surgeons who have recently completed their fellowship, focusing on surgical efficiency and clinical outcomes. From October 2022 to January 2024, 50 cases of calcaneal fractures (12 Sanders type 2, 23 type 3, and 15 type 4) were treated using the sinus tarsi approach at a single Level 1 trauma center. The cumulative sum test was employed to identify case cutoffs for key surgical parameters. Pre- and postoperative X-rays and computed tomography (CT) were analyzed to measure the Bohler angle, hindfoot varus angle, and posterior facet step-off. Operative time, intraoperative C-arm fluoroscopy use, and postoperative complications, including infections and revision surgeries, were also evaluated. Significant postoperative improvements were observed: the Bohler angle increased from 12.2 degrees to 26.3 degrees , hindfoot varus angle decreased from 15.2 degrees to 5.3 degrees , and posterior facet step-off was reduced from 14.1 mm to 0.56 mm. Consistent correction of the Bohler angle and hindfoot varus angle was achieved after 21 cases, while posterior facet step-off correction reached proficiency after 26 cases. Reduction quality was classified as Excellent (n = 24), Good (n = 13), Fair (n = 8), and Poor (n = 5), with Excellent or Good outcomes achieved consistently after 21 cases. The mean operative time was 104 min, decreasing from 124.2 min to 85.2 min after 24 cases. The average number of fluoroscopy shots was 141, decreasing from 206.4 in the first 19 cases to 95.1 thereafter. Complications included six revision surgeries, one infection, four cases of insufficient posterior facet correction, and one case of screw penetration. Novice foot and ankle surgeons can achieve surgical proficiency in the sinus tarsi approach for calcaneal fracture fixation after approximately 20 to 26 cases. This learning curve was reflected by improved operative efficiency, reduced fluoroscopy use, and consistent radiographic correction of the Bohler angle, hindfoot varus angle, and posterior facet step-off
Non-Linear Associations Between Serum Vitamin D and Uric Acid in Korean Adults: 2022–2023 KNHANES Data
No full textObjectives: This study aimed to investigate both the linear and non-linear associations between serum 25-hydroxyvitamin D [25(OH)D] levels and serum uric acid concentrations in Korean adults, with a particular focus on the vitamin D-insufficient range (<30 ng/mL), and to explore the potential metabolic implications of this relationship. Methods: Using data from the Korea National Health and Nutrition Examination Survey (KNHANES), we analyzed 10,864 adults aged 19 years and older. Serum vitamin D levels were categorized into quartiles (Q1-Q4), and their relationships with uric acid concentrations were examined using Pearson correlation, analysis of variance (ANOVA), and restricted cubic spline regression. Multivariate models were adjusted for potential confounders including age, sex, body mass index (BMI), kidney function, chronic disease status, and macronutrient intake. Results: In unadjusted analysis, a statistically significant but weak negative correlation was observed between serum 25(OH)D and uric acid levels (Pearson's r = -0.092, p < 0.001). However, in multivariate regression adjusting for confounders, a weak positive association emerged. Restricted cubic spline analysis revealed significant positive associations in the lower quartiles (Q1-Q3), with the strongest association in Q3 (beta = 0.769, 95% CI: 0.34-1.19, p < 0.001). No significant association was observed in the highest quartile (Q4). Conclusions: Serum vitamin D and uric acid concentrations show a non-linear relationship, with a significant positive association within the vitamin D-insufficient range (<30 ng/mL). These findings provide new insights into the potential metabolic role of vitamin D and highlight the need for longitudinal and interventional studies to clarify causality and clinical significance
Quantitative analysis of radial torsion angle according to location with CT scan
No full textPURPOSE: Malrotation of the radius following a shaft fracture can lead to persistent pain, limited motion, and adjacent joint instability. This study aimed to evaluate radial torsion patterns by specific location. METHODS: We included 50 patients with uninjured radii on computed tomography (CT). The torsion measuring zone (TMZ), defined along the longitudinal axis from just proximal to the watershed line to the distal end of the radial tuberosity, was divided into 3 mm intervals, generating cross-sectional images for torsion evaluation. Distal and proximal 30 mm segments were defined as distal end zone (DEZ) and proximal end zone (PEZ), respectively. The area with the largest 30 mm angular difference in distal half was designated the distal shaft torsion zone (DSTZ). The area between the proximal end of DSTZ and distal end of PEZ was the mid-shaft zone (MSZ). Angle change rate was evaluated in each zone, with the DSTZ compared to DEZ, MSZ, and PEZ. RESULTS: The cohort included 27 men and 23 women, mean age of 54.8 +/- 19.6 years. TMZ length was 160.5 +/- 16.3 mm, with torsion angle of 49.8 +/- 13.3 degrees The angle change rate was 4.6 +/- 1.9 degrees /cm in the DEZ and 5.1 +/- 3.3 degrees /cm in the PEZ. The centre of the DSTZ was 4.8 +/- 1.4 cm from distal end, with an angle change rate of 6.5 +/- 1.8 degrees /cm. The MSZ length was 6.7 +/- 1.7 cm, with angle change rate of 0.3 +/- 1.6 degrees /cm. DSTZ showed significantly higher angle change rates compared to DEZ (P < 0.001) and MSZ (P < 0.001). CONCLUSION: The DSTZ, located about 5 cm from the distal end, exhibited the most significant torsion, while the MSZ showed minimal torsion. Recognising these torsion patterns will guide proper plate positioning and prevent iatrogenic malrotation during plate osteosynthesis for radius shaft fracture
Identifying predictive markers of head and neck squamous cell carcinoma in an umbrella trial (KCSG HN 15-16 TRIUMPH trial)
No full textBACKGROUND: Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. Limited treatment options highlight the need for precision therapeutics. PATIENTS AND METHODS: We investigated the correlation between diverse clinical features and genetic changes using next-generation sequencing data derived from our recent umbrella trial. We analyzed the targeted DNA and RNA sequencing data profiles of 419 patients with HNSCC enrolled in the recent genomic-based umbrella trial. Comprehensive analyses, including survival analysis, were conducted to assess the overall genetic landscape, mutational signature patterns, copy number variations, and their correlation with patient outcomes. RESULTS: Multiple genomic aberrations served as predictive factors in patients treated with targeted therapies. NOTCH1 mutations and MYC amplification were associated with worse prognosis (P = 0.0037 and P = 0.0016, respectively). CDKN2A mutations influenced the clinical outcome of patients treated with CDK4/6 inhibitors, with divergent effects based on mutation types (improved survival with deletions and poor survival with SNV/indels). p16 positivity was correlated with a favorable prognosis in patients who underwent immunotherapy during the TRIUMPH trial. Stratification of such groups revealed novel genomic characteristics, such as mutual exclusiveness between TP53 and PIK3CA SNV/indels in HPV-positive oropharyngeal cancer, along with a high prevalence of TP53 mutations in young patients with oral-cavity cancer, which were unrelated to germline predisposing mutations, smoking habits, or p16 expression. CONCLUSION: Genomic profiling plays a significant role in the management of recurrent or metastatic HNSCC and may help identify potential targets for precision therapeutics
Colchicine and the risk of major adverse cardiovascular events in patients with gout and Type 2 diabetes: A nationwide cohort study
No full textBACKGROUND: Type 2 diabetes mellitus (T2DM) and gout are associated with an increased risk of cardiovascular events. Despite the approval for the secondary prevention of cardiovascular diseases by the United States Food and Drug Administration in 2023, evidence regarding the effectiveness of colchicine among T2DM population remains limited. OBJECTIVES: We aimed to evaluate the association between the use of colchicine and the risk of major adverse cardiovascular events (MACE) among patients with gout and T2DM. METHODS: We conducted a nationwide, population-based cohort study with active comparator, new-user design using nationwide claims data of South Korea (2010-2022). Patients with T2DM and gout who initiated colchicine or non-steroidal anti-inflammatory drugs (NSAIDs) from 2011 to 2022 were included. The primary outcome was MACE (myocardial infarction, ischemic stroke, and cardiovascular death). Secondary outcomes were each individual components of primary outcome and hospitalization due to heart failure. As-treated approach with 30-day grace period was applied. RESULTS: Before propensity score (PS) matching, 13,019 colchicine users and 111,594 NSAIDs users were included in the study cohort (mean age, 65.5 vs. 62.9; 35.0% vs. 29.8% female). After 1:2 PS matching, 12,908 colchicine users and 25,816 NSAIDs users remained (mean age, 65.7 vs. 65.7 years; 35.2% vs. 35.1% female). The PS-matched hazard ratio for MACE was 0.94 (95% confidence interval 0.65-1.36), and all secondary outcomes also resulted in null findings. CONCLUSIONS: Use of colchicine does not significantly reduce the risk of MACE compared with NSAIDs in a real-world population with T2DM and gout in South Korea between 2011 and 2022
The global, regional, and national burden attributable to low bone mineral density, 1990–2020: an analysis of a modifiable risk factor from the Global Burden of Disease Study 2021
No full textBACKGROUND: Fractures related to osteoporosis and low bone mineral density lead to substantial morbidity, mortality, and cost to individuals and health systems. Here we present the most up-to-date global, regional, and national estimates of the contribution of low bone mineral density to the burden of fractures from falls and additional categories of injuries from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. METHODS: The burden of low bone mineral density was estimated from 1990 to 2020 in terms of years lived with disability (YLDs), disability-adjusted life years (DALYs), and deaths, for individuals aged 40 years and older, using data from population-based studies from 48 countries or territories (169 unique sources). Mean standardised femoral neck bone mineral density values were estimated by GBD location, age, and sex by meta-regression. Based on a separate meta-analysis of population-based studies from nine countries (12 unique sources), we also estimated the pooled relative risk of fractures per unit decrease in bone mineral density (g/cm(2)). The population-attributable fraction for low bone mineral density was calculated by comparing the observed distributions of standardised femoral neck bone mineral density to an age-specific and sex-specific counterfactual distribution, defined as the 99th percentile of five rounds of the National Health and Nutrition Examination Survey in the USA, by 5-year age group and sex. Hospital and emergency department data were used to derive the incidence of fractures for six categories of injury (road injuries, other transport injuries, falls, non-venomous animal contact, exposure to mechanical forces, and physical interpersonal violence) using ICD codes. Deaths due to fractures were estimated as the proportion of in-hospital deaths due to the specified injury causes for which a fracture (nature of injury code) was more severe than the cause of injury code. YLDs and DALYs attributable to low bone mineral density by cause of injury were also determined according to previous GBD methods. FINDINGS: In 2020, 8.32 million (95% UI 5.58-10.84) YLDs, 17.2 million (14.1-20.2) DALYs, and 477 000 (411 000-536 000) deaths were attributable to low bone mineral density globally in individuals aged 40 years and older. Between 1990 and 2020, global YLDs, DALYs, and deaths attributable to low bone mineral density increased by 91.8% (88.5-95.1), 89.8% (81.5-99.0), and 127.1% (108.5-144.5), respectively. Over this period, the age-standardised global rates of YLDs, DALYs, and deaths attributable to low bone mineral density showed modest decreases. In 2020, falls accounted for 76.2% (95% UI 74.2-78.3) of YLDs, 65.2% (62.9-67.6) of DALYs, and 71.0% (67.4-72.8) of deaths attributable to low bone mineral density, and road injuries largely accounted for the remaining amount: 12.4% (11.1-13.6) of YLDs, 24.6% (22.5-27.1) of DALYs, and 23.1% (21.6-26.2) of deaths. As a proportion of all fall-related burden, low bone mineral density accounted for 26.6% (23.2-28.7) of YLDs, 25.6% (22.1-27.4) of DALYs, and 40.6% (35.4-44.0) of deaths in 2020. Of all road injury-related burden, 12.6% (10.8-13.5) of YLDs, 6.3% (5.4-6.9) of DALYs, and 8.9% (7.6-9.6) of deaths were attributable to low bone mineral density. In men, road injuries accounted for the largest proportion of DALYs attributable to low bone mineral density in those aged 40-59 years and the largest proportion of deaths in those aged 40-64 years. In women, road injuries were the leading cause of DALYs attributable to low bone mineral density in those aged 40-44 years and the leading cause of deaths attributable to low bone mineral density in those aged 40-54 years. In older age groups among both men and women, falls were the leading cause of the burden attributable to low bone mineral density. INTERPRETATION: Low bone mineral density is a crucial modifiable risk factor for fractures, which are an important cause of morbidity and mortality particularly in ageing populations. This analysis highlights low bone mineral density as a cause of health loss not just from falls, but also from road injuries. FUNDING: Gates Foundation
Association Between Cardiovascular Risk and Subclinical Atherosclerosis in Korean Female Patients with Systemic Lupus Erythematosus
No full textBackground: Cardiovascular disease (CVD) is a major complication of systemic lupus erythematosus (SLE). This study compared several CV risk scores in Korean female patients with SLE and searched for an association with subclinical atherosclerosis and lipid metabolism. Methods: Female SLE patients and healthy controls (HCs) underwent carotid ultrasonography and pulse wave velocity (PWV), and serum efflux cholesterol capacity was measured. The Framingham risk scores (FRSs), American College of Cardiology/American Heart Association (ACC/AHA) scores, and Korean Risk Prediction Model (KRPM) scores were calculated. Results: While carotid intima-media thickness (IMT) and the prevalence of carotid plaque did not differ between 67 SLE patients and 37 HCs, carotid plaque scores were higher in SLE patients compared with HCs. While the FRS and the ACC/AHA CV risk scores did not differ, the KRPM scores were higher in SLE patients. The carotid IMT, plaque score, and PWV were correlated with the FRS, ACC/AHA CV risk, and KRPM score in SLE patients. SLE patients with carotid plaque had higher FRS, ACC/AHA CV risk, and KRPM scores than those without carotid plaque. In addition, the serum cholesterol efflux capacity did not differ between SLE patients with and without carotid plaque but was correlated with carotid IMT. Conclusions: The scores obtained from the CV risk-prediction models were correlated with subclinical atherosclerosis in SLE. A cardiovascular risk assessment tool developed specifically for Koreans is suitable for evaluating the CV risk in Korean SLE patients
Escherichia coli gene expression is influenced more by gut environmental changes from inflammation and microbiota modulation than by colitis severity
No full textModulation of the gut microbiota has emerged as a promising diagnostic and therapeutic approach for inflammatory bowel disease (IBD), which is characterizes by chronic relapse. Analysing gene expression in luminal bacteria helps monitor the gut environment and assess the effects of probiotics. However, the complexity of the microbiota poses significant challenges. In this study, we analysed the gene expression of Escherichia coli in the intestines of IBD mouse models in the context of a native gut microbiota. We employed a reporter E. coli expressing reverse transcriptase-Cas1 fusion protein and Cas2 to record transcript data on plasmids as short oligonucleotides. Gene expression profiles differed between IBD models and controls and varied with the type of inflammatory trigger and time point. However, pre-feeding Lactobacillus crispatus prior to IBD induction resulted in E. coli gene expression profiles resembling those of controls despite exacerbation of colitis. In conclusion, altered E. coli gene expression in the inflamed gut may reflect environmental changes driven by interactions between inflammation and the microbiota. These findings suggest that bacterial gene expression adapts dynamically to the gut environment, which is shaped by host inflammatory responses and the interactions with the microbiota. These results have implications for the development of non-invasive bacterial diagnostics for gut inflammation