Review of the renal endpoints used in cardiovascular safety clinical trials in type 2 diabetes mellitus patients and their importance in primary care

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.     

Good mid-term outcome of the rotating hinge knee in primary total knee arthroplasty – Results of a single center cohort of 106 knees with a median follow-up of 6.3 years

BackgroundThe prognosis of complex primary total knee arthroplasty (TKA) with severe deformity and ligament deficiency is not clear. There is a paucity of evidence in the current literature on treatment outcomes of the rotating hinge knee implants in primary TKA. The aim of this study was to determine the mid-term clinical, radiographic, and health-related quality of life (HRQoL) outcomes in patients who had undergone complex primary TKA using single hinged knee replacement.MethodsIn total, 106 complex primary TKAs (101 patients) were performed using the single rotating hinged knee (RHK) implant design at our institution between January 2004 and December 2013. We conducted a retrospective analysis of prospectively collected outcome data of these patients, obtaining also information on all possible revision surgeries from the Finnish Arthroplasty Register, and conducted a prospective follow-up study of all living patients.ResultsThe 10-year Kaplan-Meier survival rate of the RHK knees was 91.6% (95% CI 86.0% to 97.2%) with revision for any reason as the endpoint. Overall, eight knees (7.5 %) underwent revision surgery during the follow-up. None of the unrevised RHK knees were radiographically loose. The majority of patients evinced good clinical outcome and quality of life as measured with patient reported outcome measures.ConclusionThe hinge knee replacement which was assessed current study can be regarded as a suitable option in complex primary TKA, provided adequate attention is paid to the correct indications and patient selection.     

温经汤治疗原发性痛经的网络药理学作用机制＊

目的 本文将通过网络药理学结合分子对接对温经汤治疗原发性痛经作用机制进行预测。方法 利用TCMSP、TCMID及BATMAN-TCM数据库，收集温经汤活性成分并预测其作用靶标。通过GeneCards数据库、OMIM数据库筛选原发性痛经的靶标，并运用R软件获取疾病交集靶标，绘制韦恩图。运用Cytoscape软件构建温经汤治疗原发性痛经的成分-靶标网络图，通过STRING数据库构建PPI靶标蛋白互作网络，并进行核心靶标的GO功能富集分析及KEGG通路富集分析。通过Autodock Vina软件对药物活性成分与疾病核心靶标进行分子对接验证。结果 筛选得到温经汤治疗原发性痛经的124个活性成分和31个药物-疾病共同靶标，并推断其作用机制可能与介导HIF-1、TNF、PI3K-Akt等105条信号通路相关。槲皮素、山柰酚、豆甾醇等活性成分与PTGS1、ESR1、PGR等核心靶标对接结果良好。结论 温经汤活性成分可能通过发挥镇痛、抗炎、调节激素水平、缓解平滑肌痉挛和改善缺氧状态等药理作用来治疗原发性痛经。     

Neurovascular-modulation: A review of primary vascular responses to transcranial electrical stimulation as a mechanism of action

BackgroundThe ubiquitous vascular response to transcranial electrical stimulation (tES) has been attributed to the secondary effect of neuronal activity forming the classic neurovascular coupling. However, the current density delivered transcranially concentrates in: A) the cerebrospinal fluid of subarachnoid space where cerebral vasculature resides after reaching the dural and pial surfaces and B) across the blood-brain-barrier after reaching the brain parenchyma. Therefore, it is anticipated that tES has a primary vascular influence.ObjectivesFocused review of studies that demonstrated the direct vascular response to electrical stimulation and studies demonstrating evidence for tES-induced vascular effect in coupled neurovascular systems.ResultstES induces both primary and secondary vascular phenomena originating from four cellular elements; the first two mediating a primary vascular phenomenon mainly in the form of an immediate vasodilatory response and the latter two leading to secondary vascular effects and as parts of classic neurovascular coupling: 1) The perivascular nerves of more superficially located dural and pial arteries and medium-sized arterioles with multilayered smooth muscle cells; and 2) The endothelial lining of all vessels including microvasculature of blood-brain barrier; 3) Astrocytes; and 4) Neurons of neurovascular units.ConclusionA primary vascular effect of tES is highly suggested based on various preclinical and clinical studies. We explain how the nature of vascular response can depend on vessel anatomy (size) and physiology and be controlled by stimulation waveform. Further studies are warranted to investigate the mechanisms underlying the vascular response and its contribution to neural activity in both healthy brain and pathological conditions – recognizing many brain diseases are associated with alteration of cerebral hemodynamics and decoupling of neurovascular units.     

Evaluation of the metformin initiation rate in veterans with newly identified type 2 diabetes

BackgroundAn estimated 35 million individuals in the United States have diabetes. The American Diabetes Association recommends metformin as first-line pharmacologic treatment. The primary objective of this study was to evaluate the metformin initiation rate in veterans with recently identified type 2 diabetes.MethodsVeterans with new onset type 2 diabetes were identified using National Veterans Health Administration Data. Retrospective information was obtained from those with a first A1C ≥ 6.5% (48 mmol/mol) between 2013 and 2018. Veterans with at least one additional A1C < 6.5% (48 mmol/mol) documented in the three years prior to the A1C diagnostic for diabetes were included in the analysis.ResultsA total of 144,180 veterans were included. Of those, 45,776 (31.7%) were started on metformin within one year of diabetes diagnosis. The median time to metformin initiation was 12 days and median time to initiation of any anti-hyperglycemic was 11 days. Approximately 16,000 veterans were referred for lifestyle interventions within 90 days.ConclusionMetformin initiation occurred in fewer patients than expected given metformin is a generic, well-tolerated medication recommended as first-line pharmacologic treatment option regardless of A1C. Further studies are needed to assess the barriers of initiating metformin at time of diabetes diagnosis.