Long-Term Insulin-Independence After Allogeneic Islet Transplantation for Type 1 Diabetes: Over the 10-Year Mark

Results of islet of Langerhans transplantation have markedly improved in recent years, but most patients still lose insulin independence in the long-term. We report herein the longest (over 11 years) case of insulin independence after allogeneic islet transplantation. The subject had a 27-year history of type 1 diabetes and received a single islet-after-kidney graft of 8800 islet equivalents (IEQ)/kg, pooled from 2 donors. Insulin was discontinued by 3 months posttransplant and the patient has remained off insulin ever since. Yearly follow-up studies have revealed normal metabolic control, including normal oral glucose tolerance test (OGTT). Reasons for success may involve choice of immunosuppression, low metabolic demand and low immune responsiveness as suggested by an excellent HLA matching and a high count of circulating regulatory T cells. This observation is so far an exceptional case, but clearly demonstrates the validity of the concept that long-term insulin independence after allogeneic islet transplantation is an achievable target.     

Upregulation of TNF Receptor Type 2 in Human and Experimental Renal Allograft Rejection

An important role of TNF interacting with TNFR2 has been shown in different models of ischemic, nephrotoxic and immune-mediated renal injury. To systematically evaluate the expression of TNFR2 in renal allograft rejection, we investigated human renal allograft biopsies and, in addition, established an experimental transplantation model in rats to verify the human data under standardized conditions.
The expression of TNFR2 was analyzed in 96 human renal allograft biopsies with different disease entities. In a 6-day and a 28-day experimental protocol, TNFR2 was examined in kidney specimens and in the urine of control, uni-nephrectomized and transplanted rats ± cyclosporine treatment (n = 114).
In human biopsies and in rat allografts on day 6 with acute allograft rejection, significantly elevated expression of TNFR2 was observed in tubular epithelial cells, podocytes, B cells and monocytes/macrophages. The expression level was associated with renal function. The TNFR2 expression level at day 28 was significantly lower compared to day 6.
TNFR2 is markedly upregulated both in human and experimental acute renal allograft rejection. Our data are robust and consistent between different species, suggesting a role for TNFR2 in the early course of rejection.     

绝经后肥胖女性骨密度与血管内皮功能的关系研究

目的 探讨绝经后肥胖女性中骨密度(BMD)与血管内皮功能的相关性.方法 选择自然绝经1～5年的单纯肥胖者(体重指数≥25kg/m2),年龄40～55岁,按照双能X线检测结果选择正常骨量组39例,骨量减少组37例和骨质疏松组19例.所有受试者测定体脂、BMD、骨矿含量(BMC)和血管内皮功能,包括血流介导的内皮依赖性血管舒张(EDD)和硝酸甘油介导的非内皮依赖性血管舒张.结果 骨质疏松组平均年龄和平均绝经时间显著高于正常骨量组和骨量减少组(P<0.05或P<0.01).骨质疏松组及骨量减少组BMD和BMC均显著低于正常骨量组(P<0.05或P<0.01).骨质疏松组EDD显著低于正常体重组和骨量减少组(分别为5.45±2.99、7.76±3.70和7.32±3.41,均P<0.05).相关分析显示各部位的BMD、BMC均与EDD相关(P<0.05和P<0.01).结论 肥胖女性绝经后骨质疏松与血管内皮功能异常有关,对绝经后肥胖女性低骨量人群干预治疗可能有助于防治动脉硬化及心血管疾病.     

Enteric-coated mycophenolate sodium in de novo pediatric renal transplant patients

Data on the use of enteric-coated mycophenolic acid (EC-MPS) in pediatric transplantation cases are scarce. We undertook a 12-month, multicenter, open-label pilot study in which 16 de novo renal transplant patients aged 5–16 years received EC-MPS with cyclosporine A microemulsion (CsA-ME), steroids, and anti-interleukin-2 receptor antibody induction. The mean dose of EC-MPS was 916 ± 93 mg/m² per day during weeks 1–2, 810 ± 193 mg/m² per day during months 3–6, and 827 ± 153 mg/m² per day during months 6–12. The mean CsA C₂ level exceeded target range up to month 6 post-transplant. Efficacy failure (biopsy-proven acute rejection, graft loss, death or loss to follow-up) occurred in two patients: one patient with primary non-function underwent nephrectomy, and one patient experienced biopsy-proven acute rejection (Grade 1B, day 344) following EC-MPS dose reduction. There were no deaths. Creatinine clearance (Schwartz) was 103 ± 30 mL/min per 1.73 m² at month 6 and 100 ± 16 mL/min per 1.73 m² at month 12. The majority of adverse events were mild or moderate (101/126, 80.2%). In this pilot study, EC-MPS 450 mg/m² administered twice daily with CsA, steroids, and interleukin-2 antibody induction resulted in a low rate of rejection with good renal function in a pediatric population. However, a larger, controlled trial is required to confirm these results.     

Retrospective investigation of pulmonary resection in patients with high total pulmonary vascular resistance during preoperative unilateral pulmonary artery occlusion

Purpose  The aim of this study was to evaluate the indications for pulmonary resection (lobectomy) in patients with increased total pulmonary vascular resistance (TPVR) during a preoperative unilateral pulmonary artery occlusion (UPAO) test. According to our previous report, the feasibility of performing lobectomy in patients with a high risk of cardiopulmonary complications is determined on the basis of the increase in TPVR after 15 min of obstruction during the UPAO test (occluded TPVR). Methods  A total of 19 high-risk [occluded TPVR ≥700 dynes/s/cm⁻⁵/m² (dynes)] patients who underwent lobectomy or pneumonectomy were studied and a detailed analysis of postoperative cardiopulmonary complications was performed. The subjects were divided into four groups based on the occluded TPVR (700–799 dynes, 800–899 dynes, 900–999 dynes, or ≥1000 dynes) to compare the incidence of postoperative complications. Results  Two patients died after surgery. One of them had an occluded TPVR >1000 dynes and died 313 days after right upper lobectomy; the other had an occluded TPVR of 783 dynes and died 20 days after right pneumonectomy. Postoperative cardiopulmonary complications occurred in 6 of 19 patients (31.6%), and all three patients with an occluded TPVR ≥900 dynes developed cardiopulmonary complications. Conclusion  Limited surgery should be performed in patients with an occluded TPVR ≥900 dynes.     

Genotype–phenotype correlation in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) and PKD1 mutations have a more severe disease than do patients with PKD2 mutations. The aim of this study was to compare phenotypes between children with mutations in the PKD1/PKD2 genes. Fifty PKD1 children and ten PKD2 children were investigated. Their mean age was similar (8.6 ± 5.4 years and 8.9 ± 5.6 years). Renal ultrasound was performed, and office blood pressure (BP), ambulatory BP, creatinine clearance and proteinuria were measured. The PKD1 children had, in comparison with those with PKD2, significantly greater total of renal cysts (13.3 ± 12.5 vs 3.0 ± 2.1, P = 0.004), larger kidneys [right/left kidney length 0.89 ± 1.22 standard deviation score (SDS) vs 0.17 ± 1.03 SDS, P = 0.045, and 1.19 ± 1.42 SDS vs 0.12 ± 1.09 SDS, P = 0.014, successively] and higher ambulatory day-time and night-time systolic BP (day-time/night-time BP index 0.93 ± 0.10 vs 0.86 ± 0.05, P = 0.021 and 0.94 ± 0.07 vs 0.89 ± 0.04, P = 0.037, successively). There were no significant differences in office BP, creatinine clearance or proteinuria. Prenatal renal cysts (14%), hypertension defined by ambulatory BP (27%) and enlarged kidneys (32%) were observed only in the PKD1 children. This is the first study on genotype–phenotype correlation in children with ADPKD. PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1.     

青少年精神分裂症患者生活事件及应对方式与家庭功能的相关性研究

目的探讨青少年精神分裂症患者生活事件、应对方式与家庭功能的关系。方法采用青少年生活事件量表（ASLEC）、特质应对方式问卷（TCSQ）、家庭关怀度指数量表（APGAR）,对53例青少年精神分裂症患者进行调查分析。结果36例（67．92％）青少年精神分裂症患者有家庭功能障碍。不同家庭功能患者ASLEC总分及受惩罚因子评分比较,差异有统计学意义（均P〈0．05）。消极应对与家庭功能中的合作度、亲密度呈显著负相关（均P〈0．05）;家庭关怀度指数总分与ASLEC总分存在显著负相关（P〈O．01）。结论青少年精神分裂症患者生活事件、应对方式与家庭功能有关。在对患者心理治疗和护理干预的同时,应对家庭成员进行相关干预,以提升家庭功能。     

Chaotic dynamics and convergence analysis of temporal difference algorithms with bang‐bang control

Reinforcement learning is a powerful tool used to obtain optimal control solutions for complex and difficult sequential decision making problems where only a minimal amount of a priori knowledge exists about the system dynamics. As such, it has also been used as a model of cognitive learning in humans and applied to systems, such as humanoid robots, to study embodied cognition. In this paper, a different approach is taken where a simple test problem is used to investigate issues associated with the value function's representation and parametric convergence. In particular, the terminal convergence problem is analyzed with a known optimal control policy where the aim is to accurately learn the value function. For certain initial conditions, the value function is explicitly calculated and it is shown to have a polynomial form. It is parameterized by terms that are functions of the unknown plant's parameters and the value function's discount factor, and their convergence properties are analyzed. It is shown that the temporal difference error introduces a null space associated with the finite horizon basis function during the experiment. The learning problem is only non‐singular when the experiment termination is handled correctly and a number of (equivalent) solutions are described. Finally, it is demonstrated that, in general, the test problem's dynamics are chaotic for random initial states and this causes digital offset in the value function learning. The offset is calculated, and a dead zone is defined to switch off learning in the chaotic region. Copyright © 2015 John Wiley & Sons, Ltd.     

New results on H∞ filtering for nonlinear large‐scale systems with interconnected time‐varying delays

This paper proposes a new design method of H_∞ filtering for nonlinear large‐scale systems with interconnected time‐varying delays. The interaction terms with interval time‐varying delays are bounded by nonlinear bounding functions including all states of the subsystems. A stable linear filter is designed to ensure that the filtering error system is exponentially stable with a prescribed convergence rate. By constructing a set of improved Lyapunov functions and using generalized Jensen inequality, new delay‐dependent conditions for designing H_∞ filter are obtained in terms of linear matrix inequalities. Finally, an example is provided to illustrate the effectiveness of the proposed result. Copyright © 2015 John Wiley & Sons, Ltd.     

A2/A2B to B Renal Transplantation: Past,Present, and Future Directions

One component of the new national kidney allocation system (KAS) in the United States that was implemented on December 4, 2014, was the allocation of kidneys from A₂ and A₂B (A, non‐A₁ and AB, non‐A₁B) deceased donors into blood group B candidates (A₂/A₂B → B). In so far as this is an important component of the new KAS that has the potential to further increase the access to transplantation for blood group B candidates on the waiting list, most of whom are minority candidates, we will review the body of evidence and historical perspectives that led to its inclusion in the new KAS. This review will also describe prospects for more widespread use of A₂/A₂B → B transplantation and a novel mechanism of humoral immunosuppression in B patients before and after transplantation with an A₂ or A₂B kidney.