METHODS: This was a descriptive, retrospective analysis, conducted at the Department of Paediatrics, University Malaya Medical Centre, Malaysia. All children who had esophagogastroduodenoscopy (EGD) and colonoscopy from January 2008 to June 2011 were included. An endoscopy was considered appropriate when its indication complied with the NASPGHAN and ASGE guideline. All endoscopic findings were classified as either positive (presence of any endoscopic or histologic abnormality) or negative (no or minor abnormality, normal histology); effecting a positive contributive (a change in therapeutic decisions or prognostic consequences) or non-contributive yield (no therapeutic or prognostic consequences).
RESULTS: Overall, 76% of the 345 procedures (231 EGD alone, 26 colonoscopy alone, 44 combined EGD and colonoscopy) performed in 301 children (median age 7.0 years, range 3 months to 18 years) had a positive endoscopic finding. Based on the NASPGHAN and ASGE guideline, 99.7% of the procedures performed were considered as appropriate. The only inappropriate procedure (0.3%) was in a child who had EGD for assessment of the healing of gastric ulcer following therapy in the absence of any symptoms. The overall positive contributive yield for a change in diagnosis and/or management was 44%. The presence of a positive endoscopic finding was more likely to effect a change in the therapeutic plan than an alteration of the initial diagnosis. A total of 20 (5.8%) adverse events were noted, most were minor and none was fatal.
CONCLUSION: The NASPGHAN and ASGE guideline is more likely to predict a positive endoscopic finding but is less sensitive to effect a change in the initial clinical diagnosis or the subsequent therapeutic plan.
METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.
ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.
METHODS: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL.
FINDINGS: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants.
INTERPRETATION: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention.
FUNDING: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute.
METHODS: A total of 150 adult and pediatric patients post-AHSCT were included for analysis. In addition to incidence of CMV infections, data on graft versus host disease (GVHD) were also collected. Standard hospital charges for AHSCT and any additional transplantation-related expenditure within 12 months were also retrieved in 104 patients.
RESULTS: CMV infection, acute GVHD and chronic GVHD occurred in 38.7%, 60.7%, and 22.0% of patients, respectively. Patients with CMV infections had higher readmission rates compared to those who did not (67.2% vs. 47.8%; p = 0.020). Additional expenditure was seen in HLA-haploidentical AHSCT and CMV infection (MYR11 712.25/USD2 504.49; p
METHODS: This study employed genomic methodologies to investigate the correlation between drug sensitivity and types of AICD in BC. Initially, data from TCGA were utilized to construct a prognostic model and classification system for AICD. Subsequently, a series of bioinformatics analyses assessed the prognostic and clinical significance of this model within the context of BC.
RESULTS: Analysis revealed a cohort of 18 genes associated with AICD, exhibiting prognostic relevance. Survival analyses indicated that overall survival rates were significantly lower in high-risk populations compared to their low-risk counterparts. Furthermore, prognostic indicators linked to AICD demonstrated high accuracy in predicting survival outcomes in BC. Immunological assessments indicated heightened expression of anti-tumor infiltrating immune cells and immune checkpoint molecules in low-risk populations, correlating with various anti-tumor immune functions. Ultimately, a comprehensive prognostic model related to AICD was developed through univariate analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis. As Adenosine triphosphate (ATP) concentration increased, the viability of BC cells exhibited a general decline at each time point. Notably, ATP diminished the mitochondrial membrane potential in BC cells while enhancing it in normal breast epithelial cells. Additionally, ATP inhibited the migration of BC cells and promoted their apoptosis. ATP also stimulated reactive oxygen species (ROS) production in MCF-10A cells, with implications for the immune response in BC cells. Compared to the control group, expression levels of CLIC6, SLC1A1, and CEMIP were significantly reduced in the ATP intervention group, whereas ANO6 expression was elevated. ANO6, CEMIP, and CLIC6 share genetic variants with BC, while SLC1A1 does not exhibit genetic causal variation with the disease.
CONCLUSION: A valuable prognostic model associated with AICD has been established, capable of accurately predicting BC prognosis. The induction of cell death by ATP appears to play a protective role in BC progression. These findings carry significant implications for the implementation of personalized and tailored treatment strategies for BC patients.
Methods: A total of 7180 STEMI male patients from the National Cardiovascular Disease Database-Acute Coronary Syndrome (NCVD-ACS) registry for the years 2006-2013 were enrolled. In the development of univariate and multivariate logistic regression model for the STEMI patients, Bayesian Markov Chain Monte Carlo (MCMC) simulation approach was applied. The performance of the model was assessed through convergence diagnostics, overall model fit, model calibration and discrimination.
Results: A set of six risk factors for cardiovascular death among STEMI male patients were identified from the Bayesian multivariate logistic model namely age, diabetes mellitus, family history of CVD, Killip class, chronic lung disease and renal disease respectively. Overall model fit, model calibration and discrimination were considered good for the proposed model.
Conclusion: Bayesian risk prediction model for CVD male patients identified six risk factors associated with mortality. Among the highest risks were Killip class (OR=18.0), renal disease (2.46) and age group (OR=2.43) respectively.
METHODS: An observational study was conducted among those who underwent surgery for meningioma. Eighteen subjects were recruited each for low- and high-grades, respectively. Magnetic resonance imaging (MRI) prior to surgery was employed for interpreting the Edema index and MRI after surgery was used to determine residual tumour.
RESULTS: Median age was 50 years, male to female ratio was 1:3.5, 69.4% had peritumoural brain Edema and 75% had reported gross resection. Among the reported gross total resection cases, 40.7% had residual tumour. Analysis showed statistically significant association between peritumoural brain Edema (P = 0.027) and tumour volume (P = 0.001) with high-grade meningioma, however multivariate analysis did not present any association. No association was noted between judgement of tumour resection by surgeons and peritumoural brain Edema.
CONCLUSION: Odds ratio for peritumoural brain Edema remained high and the tumour volume exhibited marginal P-value marginal significance for prediction of high grade meningioma. These two factors may still contribute to the tumour grade and should be included in further studies on the prognosis of meningioma.
METHOD: A thorough search of Ovid and Scopus databases was performed for cohort studies on PWV measurements for cardiovascular risk stratification in DM patients. Nine studies were included, examining the relationship between PWV and cardiovascular events or composite endpoints in DM patients asymptomatic of cardiovascular diseases (CVD).
RESULTS: The review revealed that optimal PWV cutoffs to predict composite cardiovascular events ranged from 10 to 12.16 m/s (aortic PWV) and 14 to 16.72 m/s (brachial-ankle PWV). In addition, meta-analysis yielded a HR of 1.15 (95 % CI 1.07-1.24, p
METHODS: A systematic search was conducted through Embase, PubMed, and Web of Science. International BMI cut-offs were employed to define underweight, overweight and obesity. The primary outcome was all-cause mortality, and the secondary outcome was respiratory and cardiovascular mortality.
RESULTS: 120 studies encompassed a total of 1 053 272 patients. Underweight status was associated with an increased risk of mortality, while overweight and obesity were linked to a reduced risk of mortality. A nonlinear U-shaped relationship was observed between BMI and all-cause mortality, respiratory mortality and cardiovascular mortality. Notably, an inflection point was identified at BMI 28.75 kg·m-2 (relative risk 0.83, 95% CI 0.80-0.86), 30.25 kg·m-2 (relative risk 0.51, 95% CI 0.40-0.65) and 27.5 kg·m-2 (relative risk 0.76, 95% CI 0.64-0.91) for all-cause, respiratory and cardiovascular mortality, respectively, and beyond which the protective effect began to diminish.
CONCLUSION: This study augments the existing body of evidence by confirming a U-shaped relationship between BMI and mortality in COPD patients. It underscores the heightened influence of BMI on respiratory and cardiovascular mortality compared to all-cause mortality. The protective effect of BMI was lost when BMI values exceeded 35.25 kg·m-2, 35 kg·m-2 and 31 kg·m-2 for all-cause, respiratory and cardiovascular mortality, respectively.
MATERIALS AND METHODS: miR-205 expression was investigated in 48 cases of inflammatory, benign and malignant tumor tissue array of the neck, oronasopharynx, larynx and salivary glands by Locked Nucleic Acid in situ hybridization (LNA-ISH) technology.
RESULTS: miR-205 expression was significantly differentially expressed across all of the inflammatory, benign and malignant tumor tissues of the neck. A significant increase in miR-205 staining intensity (p<0.05) was observed from inflammation to benign and malignant tumors in head and neck tissue array, suggesting that miR-205 could be a biomarker to differentiate between cancer and non-cancer tissues.
CONCLUSIONS: LNA-ISH revealed that miR-205 exhibited significant differential cytoplasmic and nuclear staining among inflammation, benign and malignant tumors of head and neck. miR-205 was not only exclusively expressed in squamous epithelial malignancy. This study offers information and a basis for a comprehensive study of the role of miR-205 that may be useful as a biomarker and/or therapeutic target in head and neck tumors.
OBJECTIVES: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR).
MATERIALS AND METHODS: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis.
RESULTS: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status.
CONCLUSIONS: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.
MATERIALS AND METHODS: This pilot cross-sectional survey was conducted among breast cancer survivors (n=40) who were members of Breast Cancer Support Group Centre Johor Bahru. A validated self-administered questionnaire was used to identify the relationships between socio-demography, medical characteristics and HR-QOL of the participants.
RESULTS: Living with family and completion of treatment were significant predictive factors of self-rated QOL, while living with family and ever giving birth significantly predicted satisfaction with health and physical health. Psychological health had moderate correlations with number of children and early cancer stage. Survivors' higher personal income (>MYR4,500) was the only significant predictor of social relationship, while age, income more than MYR4,500 and giving birth significantly predicted environment domain score.
CONCLUSIONS: The findings suggested the survivors coped better in all four HR-QOL domains if they were married, lived with family, had children and were employed.