20260 research outputs found
Sort by
Global Burden of Disease Due to High Body Mass Index and Projections to 2040: A Study Based on the Global Burden of Disease Study 2019
No full textBACKGROUND: The prevalence of high body mass index (BMI) contributes to an increased risk of various diseases. This study aimed to identify global disease burden trends associated with high BMI from 1990 to 2019 and forecasts up to 2040. METHODS: Using data from the global burden of disease (GBD) 2019 study, we analysed the number and ratio of disability-adjusted life years (DALYs) related to high BMI. The data were analysed by sex, ages, socio-demographic index (SDI), world health organization (WHO) region, and disease level. The autoregressive integrated moving average (ARIMA) model was employed to predict high BMI-related disease burden up to 2040. RESULTS: In 2019, the global burden of disease due to high BMI was 1932.54 (95% uncertainty interval [UI]: 1276.61, 2639.74), representing an increase of 0.18 (95% UI: 0.02, 0.42). Disease burden was consistently higher in males, middle-aged and older populations, particularly noting a narrowing gap between those aged 50-69 years and>/= 70 years in the forecast results until 2040. Additionally, regions with a middle SDI and the North Africa and Middle East WHO super-regions exhibited the highest disease burdens. Also, Cardiovascular disease ranked highest among diseases. CONCLUSION: The rising disease burden associated with high BMI highlights the need for targeted health policies focussing on older populations, low and middle-income countries, and major conditions like cardiovascular disease and diabetes. Addressing these trends requires an integrated, equity-focused approach to health planning and management to mitigate global impacts
High Neutrophil-to-Lymphocyte Ratio Predicts a Suppressive Immune Microenvironment and Basal-Like Subtype in Pancreatic Cancer
No full textBACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been utilized as a biomarker predicting prognosis in various cancers. However, it is uncertain whether NLR reflects the immunologic portrait or the molecular subtype of pancreatic cancers. METHODS: Total 64 pancreatic cancer patients who underwent surgical resection were enrolled and their preoperative serum NLR was calculated. Immunohistochemistry for CD8, CD15, CK5, and GATA6 was performed on tumor tissues to investigate the immunologic microenvironment or molecular subtype of the tumor. DeltaNp63 transfection in pancreatic cancer cell lines and subsequent cytokine array were done to investigate the mechanism. RESULTS: In the clinicopathologic analyses, high-NLR (>/= 3.29) was associated with adenosquamous histology (p = 0.009) and the significantly worse overall (p = 0.003) or disease-free survivals (p = 0.044). In line with the value of serum NLR, tumors in the high-NLR group contained more neutrophils (p = 0.0198) but fewer T lymphocytes (p = 0.0463) than in the low-NLR group. Most of the tumors in the high-NLR group were determined to be the basal-like subtype (p = 0.002). Transfection of DeltaNp63, a known key transcription factor driving the basal-like subtype, led to a substantial increase of CCL5, which is a potent chemokine to recruit neutrophils. CONCLUSIONS: High preoperative NLR is a simple but reliable biomarker predicting a worse prognosis in pancreatic cancer patients, mechanistically because this reflects a suppressive immune microenvironment and also is strongly linked to the aggressive basal-like subtype. Our study provides a rationale to use the NLR for tailored therapy as well as for predicting prognosis
Platform study of circulating tumor DNA directed adjuvant chemotherapy in colon cancer (CLAUDIA colon cancer, KCSG CO22-12)
No full textBACKGROUND: Tumor-informed circulating tumor DNA (ctDNA) analysis allows for the sensitive detection of minimal residual disease (MRD) and has the potential to enhance patient stratification for adjuvant chemotherapy. We hypothesize that intensifying adjuvant chemotherapy in colon cancer patients with postoperative MRD positivity may reduce recurrence and improve survival outcomes. METHODS: This multi-center platform trial (NCT05534087) consists of a prospective observational study (Part 1) and an interventional randomized trial (Part 2). In Part 1, approximately 1,200 patients with colon cancer will be screened for MRD at 3-6 weeks postoperatively using a tumor-informed, hybrid-capture-based ctDNA MRD assay that tracks up to 100 patient-specific somatic variants identified through tumor whole-exome sequencing. Key eligibility criteria includes: age >/= 19 years
Optimizing Vancomycin Area under the Concentration-Time Curve Targets in Enterococcal Bacteremia: Balancing Efficacy and Nephrotoxicity
No full textPURPOSE: Vancomycin is critical in treating enterococcal bacteremia; however, its optimal pharmacokinetic (PK)/pharmacodynamics (PD) targets remain unclear. This study evaluates the association between vancomycin PK/PD parameters and clinical outcomes in patients with enterococcal bacteremia. MATERIALS AND METHODS: This retrospective cohort study included 70 patients with enterococcal bacteremia treated with vancomycin at a university-affiliated teaching hospital. The primary and secondary outcomes were unfavorable clinical outcome (30-day mortality or persistent bacteremia) and nephrotoxicity, respectively. Vancomycin area under the concentration-time curve (AUC)/minimal inhibitory concentration (MIC) was calculated using Bayesian methods. Receiver operating curve (ROC) analysis determined AUC/MIC thresholds for predicting unfavorable clinical outcomes and nephrotoxicity. Logistic regression analysis identified risk factors for clinical outcomes. RESULTS: Unfavorable outcome occurred in 21 patients (30.0%), and 10 (14.3%) experienced nephrotoxicity. The ROC-derived AUC(2)(4)/MIC cutoff for unfavorable outcome and nephrotoxicity were AUC(2)(4)/MIC >/=466.0 [AUC=0.740; 95% confidence interval (CI), 0.618-0.862] and >/=643.2 (AUC=0.963; 95% CI, 0.922-1.000), respectively. Clinical success was achieved in 44.9% (22/49) of patients with an AUC(2)(4)/MIC <400, whereas 47.6% (10/21) experienced unfavorable outcome despite having an AUC(2)(4)/MIC of 400-600. Nephrotoxicity [adjusted odds ratio (aOR)=15.05; 95% CI, 2.15-105.14; p=0.006] and Charlson Comorbidity Index (CCI) (aOR=1.57; 95% CI, 1.18-2.08; p=0.002) were independent risk factors for unfavorable outcome. High AUC(2)(4)/MIC and CCI were associated with nephrotoxicity (aOR=1.03; 95% CI, 1.01-1.04; p=0.005, and aOR=1.83; 95% CI, 1.01-3.35; p=0.045). CONCLUSION: Nephrotoxicity and multiple comorbidities were stronger risk factors for unfavorable outcomes than vancomycin AUC/MIC. These findings highlight the need for individualized strategies to optimize efficacy while minimizing toxicity. Further large-scale studies are warranted to refine the optimal AUC/MIC threshold
Evaluation of mandibular bone abnormalities in patients with chronic kidney disease using cone beam computed tomography: A retrospective study
No full textOBJECTIVE: This study evaluated mandibular cortical thickness and morphological changes in chronic kidney disease (CKD) patients using cone beam computed tomography (CBCT) and their correlation with bone metabolism markers. METHODS: CKD patients were divided into CKD-I (eGFR (estimated glomerular filtration rate) < 30) and CKD-II (eGFR >/= 30) groups, with healthy controls for comparison. Mental index (MI), antegonial index (AI), and panoramic mandibular index (PMI) were compared using Kruskal-Wallis test. Mandibular cortical index (MCI) classifications, lamina dura loss, and soft tissue calcifications were assessed using Fisher's test. Relationships between serum bone metabolism markers and radiomorphometric indices were analyzed by linear regression. RESULTS: The study included 94 CKD patients (56 CKD-I, 38 CKD-II) and 88 controls. MI and AI were significantly lower in CKD-I versus controls (p < 0.05). MCI class I was less prevalent in CKD-I (5.4%) than controls (35.2%) (p < 0.001). Lamina dura loss (p = 0.006) and soft tissue calcifications (p = 0.009) occurred more frequently in CKD groups. Elevated alkaline phosphatase was associated with reduced cortical thickness (p < 0.01). CONCLUSIONS: Although findings should be interpreted considering the retrospective design's limitations, CBCT revealed significant bone abnormalities in CKD patients, with compromised bone quality and reduced mandibular cortical thickness, especially in advanced renal impairment, suggesting its value for pre-implant bone quality assessment in CKD patients
Safety and effectiveness of pregabalin controlled-release in Korean patients with peripheral neuropathic pain: A post-marketing surveillance data
No full textChronic pain, including neuropathic pain (NP), significantly affects quality of life in 7% to 10% of the general population. The prevalence of NP is rising owing to factors such as aging, obesity, and enhanced cancer survival rates. Effective management of NP is essential to improve patient outcomes. This study aimed to assess the safety and effectiveness of controlled-release (CR) pregabalin in Korean patients with peripheral NP . An open-label, non-comparative, multicenter study was conducted with 623 participants across 18 institutions. The patients received pregabalin CR as part of their routine treatment. Safety and efficacy data were collected over 12 weeks. Pain severity was assessed using the 11-point numeric rating scale (0 = no pain, 10 = worst imaginable pain), and sleep interference was assessed using an 11-point Likert scale (0 = did not interfere, 10 = unable to sleep). Safety was evaluated through adverse event (AE) reporting. Among the 617 participants evaluated for safety, 6.32% reported AEs, primarily dizziness and somnolence. Serious AEs were rare (0.32%). The efficacy analysis included 363 participants, with significant reductions in daily pain (from 5.05 +/- 2.41 to 3.16 +/- 2.26, P < .0001) and sleep interference scores (from 2.32 +/- 2.70 to 1.42 +/- 2.18, P < .0001) at week 12. Both the patients' and clinicians' global impressions demonstrated meaningful improvements in over 26% of the participants. The efficacy was reduced in patients with a medical history and in those receiving high doses (>165 mg/d). Pregabalin CR effectively reduced NP and sleep interference, with a manageable safety profile. These findings support the use of this drug as first-line treatment for NP. Personalized treatment and continuous monitoring are recommended to optimize patient outcomes
Liquid Plasma Induces Necroptosis Without Inflammatory Responses in Head and Neck Cancer Cells
No full textBACKGROUND: Several types of regulated cell deaths are known, including apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Among these types of cell deaths, apoptosis is induced by many cancer therapeutic agents. In the case of resistance, however, induction of other regulated cell death, such as necroptosis, are required. Liquid plasma, which is prepared by treatment of non-thermal plasma to solution, induces various types of regulated cell death via reactive oxygen and nitrogen species. METHODS: Liquid plasma was generated by N(2)/Ar plasma treatment in culture medium (minimum essential medium (MEM), Dulbecco's modified Eagle medium (DMEM), or Roswell Park Memorial Institute (RPMI)-1640) for 120 s per milliliter of medium (2 cm). Cell viability was determined using Cell Counting Kit-8 (CCK8), and apoptosis was determined by terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assay. Tumor necrosis factor alpha (TNF-alpha), cycloheximide (CHX), and zVAD-fmk were used to induce necroptosis in head and neck squamous cell carcinoma (HNSCC) cells, and necroptosis inhibitors, such as necrostatin-1 (Nec-1, 50 microM), GSK872 (10 microM), and necrosulfonamide (NSA, 2 microM) were used to inhibit necroptosis. Statistical comparisons between groups were carried out using the Student's t-test. RESULTS: Here, we determined the type of cell death induced by liquid plasma in head and neck cancer (HNC) cells. Our results show that liquid plasma caused necroptosis in HNC cells, and peroxynitrite in the liquid plasma might be involved in the cell death. The expression of inflammation-related molecules, including nuclear factor kappa B (NF-kappaB), interleukin (IL)-6, and mitochondrial antiviral signaling proteins, were detected in HNC cells, and treatment of HNC cells with liquid plasma decreased their expression. CONCLUSIONS: These results suggest that liquid plasma could be used to treat HNC by inducing necroptosis without inflammatory responses. In this study, we demonstrated that liquid plasma treatment may kill HNC cells without causing necroptosis-induced inflammation and inflammation-mediated diseases
Dysregulated vitamin D signaling in Hashimoto’s thyroiditis: an integrated transcriptomic study in a Korean cohort
No full textBACKGROUND: Hashimoto's thyroiditis (HT) is the most common thyroid disease leading to hypothyroidism in developed countries. Recent studies have highlighted vitamin D as a potential risk factor or therapeutic agent for HT owing to its role in modulating immune responses, although concrete evidence has not been presented. This retrospective observational study was conducted to investigate serum vitamin D levels and dysregulation of vitamin D signaling pathways in patients with HT. METHODS: Patients who underwent thyroid surgery for various thyroid neoplasm with or without HT were recruited. We analyzed serum thyroid biomarkers, including serum vitamin D, anti-thyroglobulin (TG) antibody, and anti-thyroid peroxidase (TPO) antibody for patients with HT. Using RNA-seq, the gene expression profile of thyroid tissue and the potential correlation between HT and vitamin D levels or its signaling were investigated. RESULTS: The serum vitamin D levels were significantly lower in patients with HT. However, vitamin D receptor (VDR) expression and genes involved in vitamin D-associated biological process (BP) were significantly upregulated in the HT group. Visualization of expression profile on Wikipathways revealed multifaceted regulation of vitamin D-related pathways in the HT group. Real-time PCR and immunofluorescence staining confirmed enhanced VDR expression in thyroid tissues from the HT cohort. CONCLUSION: Our study presents RNA-seq data acquired from the Korean HT cohort in this study, and highlighted dysregulated vitamin D signaling in thyroid tissues from the HT cohort. Further investigations are needed to elucidate the causal role of vitamin D signaling in the pathogenesis of HT
Combining Dopamine Transporter and Amyloid PET Tracer: A Preclinical Study on Dual-Target Imaging
No full textPURPOSE: This study aimed to evaluate the feasibility and diagnostic utility of a dual-target positron emission tomography (PET) imaging approach using a cocktail of N-3-[(18)F]fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane ([(18)F]FP-CIT) and [(18)F]florbetaben (FBB) for the simultaneous assessment of dopaminergic and amyloid changes in a preclinical setting. PROCEDURES: We utilized both Parkinson's disease (PD) and Alzheimer's disease (AD) mouse models, as well as a control group, to investigate the uptake of [(18)F]FP-CIT and [(18)F]FBB individually and in combination. PET imaging was conducted, and standardized uptake value ratios (SUVRs) were analyzed for each model across the striatal and cortical regions. Comparisons were made between single and cocktail PET scans to assess potential cross-interference of the tracers. RESULTS: In both PD and AD models, no statistically significant differences were observed in the SUVRs between single-tracer and cocktail PET scans in the striatum and cortex (p > 0.4 for striatal comparisons, p > 0.8 for cortical comparisons). Bland-Altman analysis showed no significant bias, supporting the interchangeability of SUVRs between single and cocktail PET scans. CONCLUSIONS: This preclinical study suggests that [(18)F]FP-CIT and [(18)F]FBB PET imaging is a viable dual-target imaging approach for neurodegenerative disease evaluation. The method could streamline diagnostic workflows and improve patient convenience. Further clinical studies are warranted to validate the efficacy and safety of this approach in human populations
