Clinical features and independent predictors of pulmonary arterial hypertension in systemic lupus erythematosus

Pulmonary arterial hypertension (PAH) is a devastating complication of systemic lupus erythematosus (SLE). We aim to estimate the putative predictors contributing to early identification of PAH, thus improve appropriate medical intervention and a better prognosis. A retrospective case–control study was conducted. Forty-one SLE patients with PAH and 106 SLE patients without PAH were enrolled. Demographic variables, clinical features, and laboratory data were compared between the two groups. Univariate and multivariate logistic regression models were used to examine the predictors contributing to PAH in SLE. Serositis, Raynaud’s phenomenon, high disease activity, anticardiolipin antibodies, and anti-U1RNP were significantly associated with SLE-PAH. Univariate and multivariate analysis showed that Raynaud’s phenomenon, anticardiolipin antibodies, and anti-U1RNP were independent predictors of PAH in SLE. This study highlighted the clinical pattern of SLE-PAH patients, and underlined the leading predictors of PAH development among patients with SLE. Routine echocardiography is recommended in SLE patients with the independent predictors mentioned above.     

Can increasing the prevalence of vegetable-based diets lower the risk of osteoporosis in postmenopausal subjects? A systematic review with meta-analysis of the literature

ObjectivesSeveral epidemiological investigations have assessed the association between vegetable-based diet intake (VDI) and risk of osteoporosis in postmenopausal subjects (OPS), but the outcomes have been inconsistent. We performed a review of the updated literature to evaluate this correlation.MethodsWe searched for relevant studies published in September 2018 or earlier. Two researchers conducted eligibility assessment and data extraction. Discrepancies were resolved through consultation with a third expert. Pooled odds ratios (ORs) were calculated with 95% confidence intervals (CIs).ResultsTen studies, which included 14,247 subjects, were identified. On comparing the highest category of VDI consumption with the lowest category of VDI consumption, the pooled OR for OPS was 0.73 (95% CI = 0.57–0.95), i.e., participants with a higher intake of vegetables had a 27% (95% CI = 5–43%) lower risk of OPS. Significant benefits were found on subgroup analyses of case-control studies (OR, 0.61 [95% CI, 0.48–0.78]), but not on subgroup analyses of cross-sectional studies (OR, 0.82 [95% CI, 0.57–1.16]). The synthesized effect estimates were in the direction of decreased risk of OPS on subgroup analyses of the femoral region (OR, 0.57, 95% CI = 0.41–0.80) and the lumbar spine (OR = 0.55, 95% CI = 0.38–0.81), but not on subgroup analyses of the calcaneus (OR = 0.85, 95% CI = 0.33–2.16) and the lumbar and/or femoral region (OR = 1.04, 95%CI = 0.79–1.38). Positive results were observed on pooled analyses of the Dual energy X-ray absorptiometry (DEXA) measurement method (OR, 0.72 [95% CI, 0.54–0.95]), but not on pooled analyses of the Standardized Quantitative Ultrasound (QUS) measurement method (OR, 0.85 [95% CI, 0.33–2.16]). This might have resulted from a type II error due to wide confidence intervals and less number of included studies.ConclusionThis meta-analysis seemingly confirms that higher consumption of VDI was associated with a lower risk of OPS. Taken together, these results highlight the need for future high-quality design-based trials on quantified vegetable intake and OPS.     

Decoding the Evolutionary Response to Ensartinib in Patients With ALK-Positive NSCLC by Dynamic Circulating Tumor DNA Sequencing

IntroductionBy implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.MethodsIn a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.ResultsA total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.ConclusionsOur study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.     

中药骨康含药血清培养脂肪干细胞移植促进骨质疏松性骨折愈合的研究

目的探讨中药骨康含药血清培养脂肪干细胞移植促进骨折愈合过程中骨折端骨痂的生长情况。方法制备中药骨康含药血清并进行脂肪干细胞培养,移植脂肪干细胞到骨折部位,用x线观察骨折部位骨痂生长情况。结果第3代脂肪干细胞流式鉴定CD90阳性,CD34、CD49低表达。第1、2周各组骨折愈合情况差异无统计学意义。第4周干预组的骨折已完全愈合,断端边缘消失,骨折线局部密度增高,断端的塑形改造较其他各组明显提前;对照组骨折有较多骨痂形成,但断端边缘仍可见,骨折线局部密度稍淡;空白组骨折线模糊,可见骨痂形成,断端边缘清晰可见,整体愈合情况不如干预组和对照组。干预组、对照组DR片评分与空白组比较差异有统计学意义（P〈0．05）,干预组与对照组差异亦有统计学意义（P〈0．05）。结论中药骨康含药血清培养脂肪干细胞移植可促进骨质疏松性骨折愈合。