METHODS: In this phase IIIb, open-label, multicenter study (NCT02993757), participants were randomized 1:1 to receive 3 CYD-TDV doses 6 months apart and 2 doses of quadrivalent HPV vaccine concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Only baseline dengue-seropositive participants received the 3 doses. Antibody levels were measured at baseline and 28 days after each injection using an enzyme-linked immunosorbent assay for HPV-6, -9, -16 and -18, and the 50% plaque reduction neutralization test for the 4 dengue serotypes; immunogenicity results are presented for baseline dengue-seropositive participants. Safety was assessed throughout the study for all participants.
RESULTS: At baseline, 197 of 528 (37.3%) randomized participants were dengue-seropositive [n = 109 (concomitant group) and n = 88 (sequential group)]. After the last HPV vaccine dose, antibody titers for HPV among baseline dengue-seropositive participants were similar between treatment groups, with between-group titer ratios close to 1 for HPV-6 and 0.8 for HPV-11, -16, and -18. After CYD-TDV dose 3, dengue antibody titers were similar between treatment groups for all serotypes [between-group ratios ranged from 0.783 (serotype 2) to 1.07 (serotype 4)]. No safety concerns were identified.
CONCLUSIONS: The immunogenicity and safety profiles of CYD-TDV and quadrivalent HPV vaccines were unaffected when administered concomitantly or sequentially in dengue-seropositive children.
METHODS: This single-centre retrospective observational study evaluated 2479 intensive care unit (ICU) cases from January 2016 to December 2018. A total of 76 identified candidemia cases and 76 matched control cases were analyzed. The patients' demographic characteristics and illness severity were analyzed, and possible risk factors for candidemia were investigated.
RESULTS: Multivariate logistic regression analysis identified renal replacement therapy (RRT) (odds ratio [OR]: 52.83; 95% confidence interval [CI]: 7.82-356.92; P < 0.0001), multifocal Candida colonization (OR: 23.55; 95% CI: 4.23-131.05; P < 0.0001), parenteral nutrition (PN) (OR: 63.67; 95% CI: 4.56-889.77; P = 0.002), and acute kidney injury (AKI) (OR: 7.67; 95% CI: 1.24-47.30; P = 0.028) as independent risk factors. A new prediction score with a cut-off value of 5.0 (80.3% sensitivity and 77.3% specificity) was formulated from the logit model equation.
CONCLUSIONS: Renal replacement therapy, AKI, PN, and multifocal Candida colonization were the independent risk factors for the new candidemia prediction score with high discriminatory performance and predictive accuracy.
METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols statement was used as a template for this protocol. A systematic search of Medline, Embase and Global Health from database inception to present will be conducted to identify prospective studies reporting on the associations between major measures of body composition (body mass index, waist circumference, waist-hip ratio, total body fat, visceral adiposity tissue and lean mass) and risk of heart failure. Article screening and selection will be performed by two reviewers independently, and disagreements will be adjudicated by consensus or by a third reviewer. Data from eligible articles will be extracted, and article quality will be assessed using the Newcastle-Ottawa Scale. Relative risks (and 95% CIs) will be pooled in a fixed effect meta-analysis, if there is no prohibitive heterogeneity of studies as assessed using the Cochrane Q statistic and I2 statistic. Subgroup analyses will be by age, sex, ethnicity and heart failure subtypes. Publication bias in the meta-analysis will be assessed using Egger's test and funnel plots.
ETHICS AND DISSEMINATION: This work is secondary analyses on published data and ethical approval is not required. We plan to publish results in an open-access peer-reviewed journal, present it at international and national conferences, and share the findings on social media.
PROSPERO REGISTRATION NUMBER: CRD42020224584.
METHODS: A control group of hypertensive patients only, and an investigated group of hypertensive HS patients. Fundoscopic examination to determine the grade of retinopathy was performed and then divided into low or high severity hypertensive retinopathy. Clinical and radiological parameter included are demography, vital signs, Glasgow coma scale (GCS) on admission, clot volume, site of clot, Intracerebral hemorrhage (ICH) score and Glasgow outcome scale (GOS). Data were correlated with the severity of hypertensive retinopathy.
RESULTS: Fifty patient in the control group and 51 patients in the investigated group were recruited. In the hypertensive HS group, 21 had low severity retinopathy (no or mild retinopathy) accounting for 41.2% and 30 patients had high severity (moderate or severe retinopathy). In the hypertensive patients 49 had low severity and one had high severity (p-value of 0.001). In HS group low severity showed better GCS score of 9-15 on admission (p-value of 0.003), clot volume less than 30 mL (p-value 0.001), and also a better 30 days mortality rate by using the ICH score (p-value 0.006), GOS score of 4 and 5 the low severity retinopathy fair better than the high severity retinopathy (p-value of 0.001), and the relative risk to develop HS in low severity and high severity retinopathy was 0.42 and 29.4, respectively.
CONCLUSION: Hypertensive retinopathy screening could be used as an indicator in hypertensive patient, to evaluate the risk of developing hypertensive HS in the future.
OBJECTIVE: Ternary copper (II) complex incorporated with 1-10-phenanthroline and L-tyrosine was investigated for its anti-cancer effects in HT-29 colorectal cancer cells.
METHODS: Cytotoxic effects of ternary copper (II) complex in HT-29 cells were evaluated using MTT assay, Real-Time Cell Analysis (RTCA), and lactate dehydrogenase (LDH) assay. Cell cycle analysis was performed using flow cytometry. Apoptosis induction was studied by Annexin V-FITC/propidium iodide (PI) staining and mitochondrial membrane potential analysis (JC-10 staining) using flow cytometry. Intracellular reactive oxygen species (ROS) were detected by DCFH-DA assay. The expression of proteins involved in the apoptotic signalling pathway (p53, caspases, and PARP-1) was evaluated by western blot analysis.
RESULTS: Ternary copper (II) complex reduced the cell viability of HT-29 cells in a time- and dose-dependent manner, with IC50 of 2.4 ± 0.4 and 0.8 ± 0.04 µM at 24 and 48 hours, respectively. Cell cycle analysis demonstrated induction of S-phase cell cycle arrest. Morphological evaluation and Annexin V-FITC/PI flow cytometry analysis confirmed induction of apoptosis that was further supported by cleavage and activation of caspase-8, caspase-9, caspase-3, and PARP-1. Mutant p53 was also downregulated in a dose-dependent manner. No LDH release, mitochondrial membrane potential disruption, and ROS production were observed.
CONCLUSION: Ternary copper (II) complex holds great potential to be developed for colorectal cancer treatment.
Methods: A systematic literature search was performed using the Medline, Cochrane, and Embase databases from inception to 20 October 2018. Primary outcome for meta-analyses was the changes in hepatic enzyme levels (alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase). We also performed a meta-analysis on changes in insulin resistance, glycemic, and lipid parameters using SGLT2Is as a secondary objective.
Results: Eight eligible randomized controlled studies were eligible for analysis. Meta-analysis showed the efficacy of two SLT2Is, dapagliflozin, and canagliflozin in reducing these enzymes level. TSA showed that canagliflozin significantly reduced the gamma-glutamyl transpeptidase level by weighted mean difference (-5.474, 95% confidence interval (CI): -6.289??-4.659) compared to others comparators, and the evidence is conclusive. Dapagliflozin also had a statistically significant reduction in glycated hemoglobin, which is a parameter of glycemic control and homeostatic model assessment for insulin sensitivity (HOMA-IR), which is a parameter of insulin sensitivity by a weight mean difference, -0.732 (95% CI: -1.087??-0.378) and -0.804 (95% CI: -1.336??0.272), respectively.
Conclusions: This study indicated that canagliflozin effectively improves liver function parameters among patients with diabetes, while dapagliflozin is more effective in improving glycemic indices and insulin sensitivity.