Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

金刚丸调节Hippo信号通路mRNA表达防治OVX大鼠骨质疏松作用机制

摘要：目的 基于Hippo信号通路核心基因mRNA表达，探索具有补肾填精壮骨之效的金刚丸治疗去卵巢（ovariectomized,OVX）大鼠骨质疏松症的疗效机制。方法 通过OVX法建立绝经后骨质疏松症（postmenopausal osteoporosis,PMOP）大鼠模型，分正常组、假手术组、模型组、金刚丸高剂量组、金刚丸中剂量组、金刚丸低剂量组、仙灵骨葆对照组、骨化三醇对照组。灌胃12周后，通过X射线骨密度仪检测骨密度、镜下观察股骨头显微形态结构、ELISA法检测血清ALP、实时定量RT-PCR检测骨组织Mst2、Lats1、Taz mRNA表达。结果 ①与正常组比较，模型组股骨骨密度显著降低（P＜0.01）、骨微结构显著破坏、血清ALP显著降低（P＜0.01）、骨组织Mst2、Lats1 mRNA表达显著升高（P＜0.01）、Taz mRNA表达显著降低（P＜0.01）；②与模型组比较，除金刚丸低剂量组外，各给药组的骨密度均显著升高（P＜0.01），各给药组骨微结构破坏均得到改善、血清ALP均显著升高（P＜0.01）、骨组织Mst2、Lats1 mRNA表达均显著降低（P＜0.01）、Taz mRNA表达均显著升高（P＜0.01），均以金刚丸高剂量组最为显著。结论 骨组织Hippo信号通路核心基因Mst2、Lats1 mRNA表达上调，Taz mRNA表达下调可能是PMOP的发病机制之一；金刚丸可能通过下调骨组织Hippo信号通路核心基因Mst2、Lats1 mRNA表达、上调Taz mRNA表达的机制，有效防治PMOP。     

Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

足趾移植长手指全形再造术的临床应用

目的探讨足趾移植长手指全形再造手术的临床疗效。方法自2015年6月至2019年6月,对16例因外伤致手指缺损患者采用足趾移植长手指全形再造术,术后评估供区及受区的感觉功能、运动功能及外观形态,分析指甲畸形及增生性瘢痕的发生情况,并记录术后发生感染、血肿、皮片坏死及供区愈合不良等情况;通过调查问卷的方式分析患者的满意度。结果所有患者术后获随访1~12个月,其中2例受区发生感染,1例受区皮片边缘发生坏死,经换药后予以缓解;其余患者的供、受区均未出现长时间的痛疼感觉,受区感觉功能恢复达87.50%,受区运动功能恢复均较满意,手指外形基本满意。供区感觉受影响者2例,运动功能受限者1例,外形一般者2例。所有患者无指甲畸形及增生性瘢痕发生;满意者1例,基本满意者14例,不满意者1例。结论采用足趾移植长手指全形再造手术,基本可以满足患者及医师对于缺损手指进行完美修复的目标。     

Efficacy and Feasibility of Allogeneic Hematopoietic Stem-Cell Transplantation in the Treatment of Refractory Acute Myeloid Leukemia

Background

Refractory acute myeloid leukemia (AML) includes AML includes failure of disease to respond to standard induction chemotherapy, relapse within 6 months after first CR, and 2 or more relapses. The outcome of these patients is usually very poor; only a small proportion can be rescued by allogenic hematopoietic stem-cell transplantation (allo-HSCT). The aim of this study was to evaluate the efficacy and feasibility of allo-HSCT in patients with refractory AML.