Effects of synthetic and biological disease modifying antirheumatic drugs on lipid and lipoprotein parameters in patients with rheumatoid arthritis

BackgroundDyslipidemia in rheumatoid arthritis (RA) patients is frequently observed, and treatment with anti-rheumatic drugs has an impact on lipid profiles. Pathophysiologically, inflammation leads to decreased blood lipids and lipoproteins; RA treatment reduces inflammation and therefore may increase lipids and lipoproteins. Whether the lipid changes with RA treatment confer an increased risk of cardiovascular disease or just reflect their potentially atheroprotective anti-inflammatory effect is currently unclear due to limited and conflicting data.ObjectiveThe aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid and lipoprotein parameters.ResultsRecent studies on methotrexate emphasize its anti-atherogenic effect. Golimumab combined with methotrexate revealed a trend towards an anti-atherogenic potential. The known pro-atherogenic lipid-spectrum alterations caused by tofacitinib can be effectively treated with atorvastatin. Tocilizumab signals a favorable impact on the extent of lipid modifications when combined with methotrexate. Abatacept indicated a trend towards an anti-atherogenic lipid profile demonstrated by favorable effects on HDL-C and on the TC/HDL-C ratio. Rituximab has beneficial effects on HDL-C and ApoA1, as well as on the ApoB/ApoA1 ratio.Clinical implicationsAnti-rheumatic drugs have various effects on lipid parameters, which in part appear pro-atherogenic. However, because many of these lipid changes may well reflect their potentially atheroprotective anti-inflammatory action the cardiovascular impact of these changes remains unclear. Whatsoever, cardiovascular safety trials for antirheumatic drugs would be valuable.     

早期新生儿死亡病因学研究进展

早期新生儿死亡属于围产儿死亡的一部分,其定义为新生儿出生后0~6天死亡。通常认为男性新生儿、先天异常、早产、低出生体重和5分钟Apgar评分低于7分等是早期新生儿死亡最常见的相关因素。但是仍有相当多的早期新生儿死亡病因不明,其为产科及儿科医务人员比较棘手的问题,也容易引发医患矛盾。近年来发现,除上述常见的病因外,基因缺陷和代谢性疾病在早期新生儿死亡中亦占有相当的比例,而通过全基因测序和串联质谱检测技术,可能对寻找部分既往被归于不明原因早期新生儿死亡病例的病因有一定的帮助。该文就早期新生儿死亡病因及可能机制、病因评估方法等进行综述。     

Transurethral laser versus open simple prostatectomy for large volume prostates: a systematic review and meta-analysis of randomized controlled trials

The benefit of transurethral laser prostatectomy over open simple prostatectomy (OSP) is controversial in aged symptomatic benign prostatic hyperplasia (BPH) patients with large volume prostates, and the aim of this study is to compare the safety and efficiency of these two methods. Meta-analysis was applied using the Review Manager V5.3 software and the retrieved randomized controlled clinical trials (RCTs) comparing transurethral laser prostatectomy with OSP were analyzed for the treatment of large volume prostates from 2000 to 2019 in PubMed, Web of Science, Cochrane, and EMBASE datasets. Five RCTs assessing transurethral laser prostatectomy versus OSP were considered suitable for this meta-analysis, which included a total of 448 patients, with 232 patients undergoing laser and 216 patients undergoing OSP. Compared with OSP, although transurethral laser prostatectomy required a longer operative time (weighted mean difference (WMD) 27.49 mins; 95% confidence interval (CI) 16.54–38.44; P?<?0.00001) and obtained a less resected prostate weight (WMD ??11.72 g; 95% CI ??21.75 to ??1.70; P?=?0.02), patients undergoing laser prostatectomy benefited from significantly less hemoglobin decline (??0.97 g/dL; 95% CI ??1.31 to ??0.64; P?<?0.00001), shorter time of catheterization (WMD ??3.67 days; 95% CI ??5.60 to ??1.75; P?=?0.0002), shorter length of hospital stay (WMD ??4.75 days; 95% CI ??6.57 to ??2.93; P?<?0.00001), and less blood transfusion (odds ratio 0.10; 95% CI 0.03 to 0.35; P?=?0.0003). During postoperative follow-up, no significant difference was observed between the two groups in IPSS, QoL, Q_max, and PVR. Both transurethral laser prostatectomy and OSP are safe and effective for large prostates that require prostate resection. Taking into account of less blood loss, shorter catheterization time and hospital stay, and less blood transfusion, transurethral laser prostatectomy may be a better treatment for patients with large prostates.

     

Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (μCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. μCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).     

An Orthotopic Liver Transplantation Patient Survived Without Hepatic Artery Flow Due to Thrombosis: A Case Report

BackgroundHepatic artery thrombosis (HAT), a serious complication after orthotopic liver transplantation, almost always leads to morbidity and mortality without urgent revascularization or retransplantation, especially if HAT occurs within a few days after transplantation.Case PresentationHerein we describe a case report of an orthotopic liver transplantation patient surviving without hepatic artery flow due to HAT on postoperative day 1. Reanastomosis, thrombectomy, and intra-arterial thrombolysis were performed, but only retrograde arterial flow by Doppler ultrasound, not by angiography, could be demonstrated in the hepatic artery. This case report is in compliance with the Declaration of Helsinki and the Declaration of Istanbul.ConclusionBased on the evidence from this patient, we believe that patients with failed revascularization can experience a long-term survival with conservative treatment. Retransplantation should be evaluated based on laboratory findings because graft function in individual patients can recover.     

The role of bDMARDs in idiopathic inflammatory myopathies: A systematic literature review

Idiopathic inflammatory myopathies (IIM) are a group of different conditions typically affecting striate muscle, lung, joints, skin and gastrointestinal tract. Treatment typically relies on glucocorticoids and synthetic immunosuppressants, but the occurrence of refractory, difficult to treat, manifestations, may require more aggressive treatment, borrowed from other autoimmune diseases, including biologic disease modifying drugs (bDMARDs). In this regard, we conducted a systemic literature review in order to depict the current evidence about the use of bDMARDs in IIM. A total of 78 papers, published during the last 21 years, were retrieved. The majority of patients was treated with TNF-α inhibitors, whose effectiveness was assessed particularly in recalcitrant striate muscle, skin and joints involvement. Rituximab, whose evidence is supported by a large number of real-life studies and trials, seems to be an excellent option in case of ILD and anti-synthetase syndrome, while Tocilizumab, despite not meeting primary and secondary endpoints in a recently published clinical trial, proved its effectiveness in rapidly progressing ILD. Similarly, Abatacept, studied in a phase IIb clinical trial with conflicting evidence, was reported to be effective in some case reports of refractory dermatomyositis. Less data exist for anti-IL1 and anti-IL23 agents, which were employed particularly for inclusion body myositis and severe skin disease, respectively. This study provides an organ-focused assessment of bDMARDs in IIM, which display encouraging results in the treatment of refractory subsets of disease.