The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown.
To investigate the risk of osteoporotic fracture with dabigatran vs warfarin ...in patients with NVAF.
Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016.
Dabigatran or warfarin use during the study period.
Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated.
Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean SD age, 74 11 years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users 1.0%; 72 warfarin users 1.5%). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 95% CI, -0.38 to -0.86; IRR, 0.38 95% CI, 0.22 to 0.66). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 95% CI, -2.40 to -3.45; IRR, 0.12 95% CI, 0.04 to 0.33), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 95% CI, 0.67 to -0.39; IRR, 0.95 95% CI, 0.45 to 1.96) (P value for interaction, <.001).
Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.
This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the ...next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients' clinical outcome on day 1 and day 5 of hospital admission.
We did a retrospective analysis of a complete cohort of 1037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers' readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5.
The 1037 patients had a mean age of 37.8 (SD ± 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients' disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model's accuracy rate, macro-/micro-averaged sensitivity and specificity were 91.3%, 84.9%/91.3% and 96.0%/95.7% respectively, as compared to 94.2%, 95.9%/94.2% and 97.8%/97.1% under Day-5 model.
Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients' outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care.
The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of ...the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing endogenous secretory RAGE (esRAGE) and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE.
Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE).
RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c.
Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE.
Stroke thrombolysis with alteplase is currently recommended 0–4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with ...symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.
In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale mRS score 0–1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036.
We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio OR 1·86, 95% CI 1·15–2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten 5% of 213 patients vs one <1% of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23–76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81–2·96, p=0·66).
Patients with ischaemic stroke 4·5–9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.
None.
Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the ...purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy.
Aims/hypothesis
Galectin-3 has been implicated in cardiac and renal fibrosis and serves as a prognostic clinical indicator in heart failure. The aim of the present study was to evaluate whether serum ...galectin-3 level is associated with progressive kidney disease in type 2 diabetes.
Methods
Galectin-3 was measured in baseline samples by ELISA in 1320 participants with type 2 diabetes with eGFR ≥30 ml min
−1
1.73 m
−2
. The primary outcome was defined as doubling of serum creatinine and/or initiation of renal replacement therapy during follow-up. The secondary outcome was progression to macroalbuminuria in individuals with normo- or microalbuminuria at baseline.
Results
Serum galectin-3 levels were significantly increased in a random subgroup of 270 type 2 diabetic individuals with eGFR >60 ml min
−1
1.73 m
−2
compared with an age- and sex-matched non-diabetic control group (7.58 ± 2.29 ng/ml vs 6.10 ± 1.91 ng/ml, respectively,
p
< 0.01). In the whole diabetic cohort, after a mean follow-up of 9 years, galectin-3 was independently associated with doubling of serum creatinine (HR 1.19; 95% CI 1.14, 1.24,
p
< 0.001) and incident macroalbuminuria (HR 1.20; 95% CI 1.12, 1.30,
p
< 0.001), even after adjusting for traditional risk factors, baseline eGFR and albuminuria status. Individuals with galectin-3 levels in the highest quartile had a fourfold risk of renal function loss and threefold risk of incident macroalbuminuria.
Conclusions/interpretation
Serum galectin-3 was independently associated with progressive renal disease in type 2 diabetes. Further mechanistic studies are warranted to determine whether galectin-3 is simply a disease biomarker or is also a mediator of the development and progression of diabetic nephropathy.
Aims
Recent clinical studies have shown that galectin‐3 is a prognostic indicator in patients with coronary heart disease and in patients with heart failure. Experimental data suggest that galectin‐3 ...may play a role in atherogenesis. We have evaluated whether serum galectin‐3 level is associated with cardiovascular outcome in type 2 diabetes.
Materials and methods
Galectin‐3 was measured in baseline samples in 1495 persons with type 2 diabetes. The primary cardiovascular outcome, incident cardiovascular events, was defined as first non‐fatal myocardial infarction, non‐fatal stroke, coronary revascularization, or death from cardiovascular cause. The secondary outcome was all‐cause mortality.
Results
At baseline, 12% of the subjects had prevalent cardiovascular disease. Serum galectin‐3 was increased in the group with incident cardiovascular events compared with those who remained free of events during follow up (9.03 ± 2.98 ng/mL vs 8.15 ± 2.76, P < 0.01). Serum galectin‐3 was also significantly increased in those subjects with a fatal outcome. The hazard ratios (HR) for cardiovascular events and all‐cause mortality for individuals in the top quartile were 2.50 (95% CI 1.87, 3.36, P < 0.001) and 3.92 (95%CI 2.55, 6.01, P < 0.001), respectively. In a multivariate Cox regression analysis including traditional risk factors, log (eGFR), baseline albuminuria, and cardiovascular disease status, the HR per standard deviation change in galectin‐3 was 1.13 (95% CI 1.02, 1.26, P = 0.02) for cardiovascular events and 1.17 (95% CI 1.01, 1.35, P = 0.04) for all‐cause mortality.
Conclusions
Serum galectin‐3 is associated with adverse cardiovascular outcomes in persons with type 2 diabetes independent of traditional risk factors.
Reverse micellar dyeing of cotton fabrics with PEG-based non-ionic surfactant in heptane non-aqueous medium with the use of reactive dyes with different reactive groups was investigated. Single ...jersey knitted fabrics were used in this study. The experimental results reveal that samples dyed by both one-bath and two-bath heptane reverse micellar methods can achieve higher colour yield than the conventional water-based dyeing method. Among different reactive dyes, samples dyed with hetero-bifunctional vinylsulfone based reactive dyes could achieved higher colour yield (K/S) than the homo-bifunctional and monofunctional reactive dyes in non-aqueous dyeing medium. Moreover, the ranges of L*, a* and b* value for hetero-bifunctional vinylsulfone based reactive dyes were narrower than homo-bifunctional and monofunctional reactive dyes. In term of levelness, monofunctional reactive dyes generally resulted a better levelness than homo-bifunctional and hetero-bifunctional reactive dyes. Although one-bath heptane method yields high K/S
sum
values, the problem of unlevelness should be considered while the use of two-bath heptane reverse micellar method can strike a balance between levelness and colour yield.
Graphical abstract
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