Biological Disease-Modifying Antirheumatic Drugs and Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis: A Danish Cohort Study

ObjectivesClinical trials have shown a beneficial effect from biological disease-modifying antirheumatic drugs (bDMARDs) on hand or axial bone loss in patients with rheumatoid arthritis; however, it is unclear if this translates to a reduced fracture risk. We investigated the effect of bDMARDs on osteoporotic fracture risk compared to no biological treatment in rheumatoid arthritis.MethodsA cohort of patients with rheumatoid arthritis aged 18+ from DANBIO was linked to population-based health registries in Denmark (2006-2016). Adopting a prevalent new-user design, we matched bDMARD users to bDMARD-naïve patients using time-conditional propensity scores. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, and forearm) was estimated among the matched patients by Cox proportional hazards models.ResultsOut of 24,678 patients with rheumatoid arthritis, 4265 bDMARD users were matched to the same number of bDMARD-naïve patients (mean age 56.2 years, 74% female). During follow-up, 229 osteoporotic fractures occurred among bDMARD users and 205 fractures among bDMARD-naïve patients (incidence rates 12.1 and 13.0 per 1000 person-years, respectively). The use of bDMARDs was not associated with a reduced risk of osteoporotic fractures among patients with rheumatoid arthritis (hazard ratio 0.97, 95% confidence interval 0.78-1.20), compared with no biological treatment. The risk estimates were similar for all osteoporotic fracture sites.ConclusionWe found no independent beneficial effect from using bDMARDs on reducing the risk of osteoporotic fractures in patients with rheumatoid arthritis.     

The Morphology of Coronary Artery Disease in South Asians vs White Caucasians and Its Implications

South Asians (SAs) experience a higher prevalence and earlier onset of coronary artery disease and have worse outcomes compared with White Caucasians (WCs) following invasive revascularisation procedures, a mainstay of coronary artery disease (CAD) management. We sought to review the differences in the CAD pattern and risk factors between SA and WC patients and to discuss their potential impact on the development of coronary disease, acute coronary syndrome, and revascularisation outcomes. SAs have a more diffuse pattern with multivessel involvement compared with WCs. However, less is known about other morphologic characteristics, such as calcification of atherosclerotic plaque and coronary diameter in SA populations. Despite a similar coronary calcification burden, higher noncalcified plaque composition, elevated thrombosis, and inflammatory markers likely contribute to the disease pattern. Although the current evidence on the role of coronary vessel size remains inconsistent, smaller diameters in SAs could play a potential role in the higher disease prevalence. This is especially important given the impact of coronary artery diameter on revascularisation outcomes. In conclusion, SAs have a unique CAD risk profile composed of traditional and novel risk factors. Our findings highlight the need for additional awareness of health professionals of this specific risk profile and potential therapeutic targets, as well as the need for further research in this vulnerable population.     

SLC及其受体CCR7与Ⅰ期非小细胞肺癌淋巴结微转移的相关性

目的 探讨溶质载体蛋白（SLC）及其受体趋化因子受体7（CCR7）与I期非小细胞肺癌（NSCLC）淋巴结微转移的相关性。方法 选取2019年1月~2020年3月于我院就诊的I期NSCLC患者127例为研究对象，按照淋巴结微转移情况分为对照组92例和转移组35例，所有患者入院后均通过根治术切除病灶，通过免疫组化方式检测病灶中SLC7A11及CCR7含量，并收集患者临床资料、实验室检查资料及影像学检查资料。通过Logistic回归分析评价SLC7A11及CCR7与淋巴结微转移之间的关系。最后通过建立ROC曲线分析两者及其联合检测对NSCLC患者微淋巴结转移的预测价值。结果 两组患者SLC7A11及CCR7表达水平存在显著差异（P＜0.05）。转移组患者病灶直径、支气管受累及TLG显著高于对照组（P＜0.05）。病灶直径（OR=49.254,95%CI=11.062~507.604）是影响NSCLC淋巴结微转移的独立危险因素（P＜0.05）。SLC7A11（OR=8.622）及CCR7（OR=8.709）表达水平是影响NSCLC淋巴结微转移的独立因素（P＜0.05）。SLC7A11、CCR7及联合诊断对NSCLC淋巴结微转移具有较好的检测价值（均P＜0.05）。联合检测特异度显著高于 SLC7A11及CCR7单独检测（2=7.292，15.125；均P＜0.01）。结论 SLC家族的中SLC7A11及其受体CCR7与NSCLC患者微淋巴结转移显著相关。     

Double deficiency of cathepsin B and L in the mouse pancreas alters trypsin activity without affecting acute pancreatitis severity

BackgroundPremature intracellular trypsinogen activation has long been considered a key initiator of acute pancreatitis (AP). Cathepsin B (CTSB) activates trypsinogen, while cathepsin L (CTSL) inactivates trypsin(ogen), and both proteins play a role in the onset of AP.MethodsAP was induced by 7 hourly intraperitoneal injections of cerulein (50 μg/kg) in wild-type and pancreas-specific conditional Ctsb knockout (Ctsb^Δpan), Ctsl knockout (Ctsl^Δpan), and Ctsb;Ctsl double-knockout (Ctsb^Δpan;Ctsl^Δpan) mice. Pancreatic samples were collected and analyzed by histology, immunohistochemistry, real-time PCR, and immunoblots. Trypsin activity was measured in pancreatic homogenates. Peripheral blood was collected, and serum amylase activity was measured.ResultsDouble deletion of Ctsb and Cstl did not affect pancreatic development or mouse growth. After 7 times cerulein injections, double Ctsb and Ctsl deficiency in mouse pancreases increased trypsin activity to the same extent as that in Ctsl-deficient mice, while Ctsb deficiency decreased trypsin activity but did not affect the severity of AP. Ctsb^Δpan;Ctsl^Δpan mice had comparable serum amylase activity and histopathological changes and displayed similar levels of proinflammatory cytokines, apoptosis, and autophagy activity compared with wild-type, Ctsb^Δpan, and Ctsl^Δpan mice.ConclusionDouble deletion of Ctsb and Ctsl in the mouse pancreas altered intrapancreatic trypsin activity but did not affect disease severity and inflammatory response after cerulein-induced AP.