IMPORTANCEThe risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown.OBJECTIVE To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF. DESIGN, SETTING, AND PARTICIPANTSRetrospective 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.EXPOSURES Dabigatran or warfarin use during the study period. MAIN OUTCOMES AND MEASURESRisk 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. CONCLUSIONS AND RELEVANCE 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.

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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.

The use of ICD-9 code algorithm to identify major osteoporotic fracture in CDARS is a valid tool with a very high PPV. However, cautious interpretation is required when the study focuses on incident vertebral fracture. Copyright © 2017 John Wiley & Sons, Ltd.

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.

BackgroundThe 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.MethodsConstitutive 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).ResultsRAGE 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.ConclusionOur 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.

Familial hypercholesterolemia (FH) is the most common monogenic disorder associated with premature atherosclerotic cardiovascular disease. Early diagnosis and effective treatment can significantly improve prognosis. Recent advances in the field of lipid metabolism have shed light on the molecular defects in FH and new therapeutic options have emerged. A search of PubMed database up to March 2020 was performed for this review using the following keywords: “familial hypercholesterolemia”, “diagnosis”, “management”, “guideline”, “consensus”, “genetics”, “screening”, “lipid lowering agents”. The prevalence rate of heterozygous FH is approximately 1 in 200 to 250 and FH is underdiagnosed and undertreated in many parts of the world. Diagnostic criteria have been developed to aid the clinical diagnosis of FH. Genetic testing is now available but not widely used. Cascade screening is recommended to identify affected family members and the benefits of early interventions are clear. Treatment strategy and target is currently based on LDL cholesterol levels as the prognosis of FH largely depends on the magnitude of LDL cholesterol lowering that can be achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment and are cost-effective. Addition of newer medications like PCSK9 inhibitors is able to further lower LDL cholesterol levels substantially but the cost is high. Lipoprotein apheresis is indicated in homozygous FH or severe heterozygous FH patients with inadequate response to cholesterol-lowering therapies. In conclusion, FH is a common treatable genetic disorder and although our understanding of this disease has improved, many challenges still remain for its optimal management.

Objective: Occurrence of Graves’ disease and Hashimoto’s thyroiditis after coronavirus disease 2019 (COVID-19) raised the concern about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggering thyroid autoimmunity. Uncertainties remain regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. We carried out a prospective study to characterize the evolution of thyroid function and autoimmunity among COVID-19 survivors. Method: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for confirmed COVID-19 from 21 July to 21 September 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission and at 3 months. Positive anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) was defined by &gt;100 units. Results: Among 200 COVID-19 survivors, 122 had reassessment thyroid function tests (TFTs) (median age: 57.5 years; 49.2% men). Baseline characteristics of patients who did and did not have reassessment were comparable. Among the 20 patients with baseline abnormal TFTs on admission, mostly low fT3, 15 recovered. Of the 102 patients with normal TFTs on admission, two (2.0%) had new onset abnormal TFTs, which may represent TFTs in different phases of thyroiditis (one had mildly elevated TSH 5.8 mIU/L, with normal fT4 [16 pmol/L] and fT3 [4.3 pmol/L], the other had mildly raised fT4 25 pmol/L with normal TSH [1.1 mIU/L] and fT3 [4.7 pmol/L]). Among 104 patients with anti-thyroid antibody titers reassessed, we observed increases in anti-TPO (baseline: 28.3 units [IQR 14.0-67.4] vs reassessment: 35.0 units [IQR: 18.8-99.0]; p&lt;0.001) and anti-Tg titers (baseline: 6.6 units [IQR 4.9-15.6] vs reassessment: 8.7 units [IQR: 6.6-15.4]; p&lt;0.001), but no change in anti-TSHR titer (baseline: 1.0 IU/L [IQR: 0.8-1.2] vs reassessment: 1.0 IU/L [IQR: 0.8-1.3]; p=0.486). Of the 82 patients with negative anti-TPO at baseline, 16 had significant interval increase in anti-TPO titer by &gt;12 units (2×6 [precision of the anti-TPO assay in normal range being 6 units per SD]), of these, four became anti-TPO positive. Factors associated a significant increase in anti-TPO titer included worse baseline clinical severity (p=0.018), elevated C-reactive protein during hospitalization (p=0.033), and higher baseline anti-TPO titer (p=0.005). Conclusion: Majority of thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis could occur during convalescence, though uncommon. Importantly, we provided the novel observation of an increase in anti-thyroid antibody titers post-COVID-19, suggesting the potential of SARS-CoV-2 in triggering thyroid autoimmunity, which warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.