New developments in immunosuppressive therapy in renal transplantation

The introduction of new immunosuppressive agents and protocols has improved outcomes for renal transplant recipients by decreasing the risk of rejection and by increasing the function and lifespan of the allograft. This article reviews the major changes in the combinations of therapies used: calcineurin inhibitors, target of rapamycin inhibitors, mycophenolate mofetil, non-depleting monoclonal versus depleting monoclonal and polyclonal antibodies for induction and increasing emphasis on protocols for reduction or avoidance of steroids and calcineurin inhibitors. The new agents with novel immunological targets such as anti-CD40 ligand, LEA29Y, FTY720, anti-CD20 (rituximab, Rituxan?, Mabthera?) and anti-CH52 (alemtuzumab, Campath?), which are under development but have yet to survive the rigors of clinical trials are also discussed. In the presence of low early rejection rates, immunosuppressive therapy is setting new goals such as better graft function (glomerular filtration rates), reduction in adverse effects such as hypertension, hyperlipidaemia and drug toxicity and, above all, the prevention of late graft deterioration.     

Outcomes of Donation After Circulatory Death Heart Transplantation in Australia

Background

Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice.

Caregiver-Care Recipient Relationship Closeness is Associated With Neuropsychiatric Symptoms in Dementia

Objective

Closer caregiver-care recipient (CG-CR) relationships are associated with better cognitive and functional abilities, activities of daily living (in persons with dementia), and lower informal care costs.

Poor immune response to coronavirus disease vaccines in decompensated cirrhosis patients and liver transplant recipients

Background and aimsRecent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs.MethodsIn this single-center prospective study, consecutive completely vaccinated (ChAdOx1 or BBV152) non-cirrhosis CLD patients, those with cirrhosis, and LTRs were compared with matched healthy controls for anti-spike antibody and cellular response.ResultsSixty healthy individuals, 50 NCCLD patients, 63 compensated and 50 decompensated cirrhosis, and 17 LTRs were included. The proportion of non-responders was similar among the healthy control (8 %), non-cirrhosis CLD (16 %), and compensated cirrhosis groups (17.5 %;p = 0.3). However, a higher proportion of patients with decompensated cirrhosis (34 %) and LTRs (59 %) were non-responders than the healthy controls (p = 0.001). Cluster of differentiation (CD) 4-effector cells were lower in patients with non-cirrhosis CLD and compensated cirrhosis. CD4-naïve, CD4-effector, B, and B-memory cells were lower in the decompensated cirrhosis group. Although the central memory cells were higher in the decompensated cirrhosis group, they could not differentiate into effector cells. CD4- and CD8-naïve cells were higher in the marrow in the LTRs, while the CD4-effector memory cells and CD4- and CD8-effector cells were lower in the LTRs. Furthermore, B cells were more deficient in the LTRs, suggesting poor antibody response.ConclusionPatients with decompensated cirrhosis and LTRs demonstrated suboptimal humoral and cellular immune responses against recombinant and inactivated COVID-19 vaccines.     

双胎输血综合征宫内治疗后供血胎和受血胎预后的比较

[目的]评价双胎输血综合征(TTTS)经不同治疗方式,包括羊水减量术(SA)、双极脐带电凝减胎术(BCC)和胎盘吻合血管激光凝固术(LCPV)后,供血胎和受血胎的临床结局.[方法]回顾性分析2008年1月至2013年12月在我院诊断治疗的双胎输血综合征93例,追踪妊娠结局和新生儿情况,分析比较供血胎和受血胎的临床结局.[结果]不同治疗方式组中严重的TTTS(TTTSⅢ期及以上)所占比例分别是:羊水减量术组50.0％(27/54),脐带电凝减胎术组93.9％(31/33),胎盘吻合血管激光凝固术组83.3％(5/6),P＜0.001,因此,3种治疗方式妊娠结局比较时仅纳入TTTSⅢ期及以上病例.SA组、BCC组和LCPV组双胎总体存活率分别是53.7％、24.2％和60.0％,P=0.002.SA组、BCC组和LCPV组分娩孕周中位数分别是31e(20+3～38+2)、28+5(20+2～38+6)和27+6((23+3～37+4)周,其差异无统计学意义(P=0.204).SA组胎膜早破的发生率是29.6％而BCC组和LCPV组胎膜早破的发生率分别是32.3％和60.0％,P=0.410.LCPV组28周前分娩的比例较SA组和BCC组高(分别是60.0％、18.5％和48.4％;P=0.033).TTTS双胎中受血胎存活率是44.1％(41/93)而供血胎存活率是46.2％(43/93),P=0.768;受血胎神经系统发育迟缓发生率是2.4％(1/41)而供血胎神经系统发育迟缓发生率是11.6％(5/43),其差异无统计学意义(P=0.202).[结论]胎盘吻合血管激光凝固术可提高TTTS的总体存活率;TTTS受血胎和供血胎的预后无明显差异.     

Limited surgical resection for graft salvage following recovery from complicated exfoliative rejection in pediatric intestinal recipients

Complications of ER contribute significantly to morbidity and mortality following intestinal transplantation. The surgical management of three pediatric patients who experienced complications of late ER after composite LSB transplantation is described, highlighting the potential for allograft salvage after limited surgical resection. A retrospective case series was compiled. Data collected included time to ER from transplant, medical management of ER, complications, and surgical management of ER complications. All patients had undergone composite LSB transplantation between one and two yr of age. Time to ER after transplantation was 9.5–26.5 months. ER complications included ileal allograft stricture, intramural hematoma with perforation of jejunal allograft, and massive GI hemorrhage secondary to focal ulceration and pseudopolyp formation. With evidence of mucosal regeneration, all three patients underwent limited segmental allograft resection. Two patients continue to maintain satisfactory allograft function 39–44 months following operation. The third patient retained adequate allograft function until he developed PTLD, subsequently dying from disseminated Adenovirus infection 51 months after resection. Severe disruption of intestinal allograft integrity in ER can lend itself to medically refractory complications. Prompt recognition and surgical correction of complications can play a crucial role in allograft salvage and patient survival after ER.     

Respiratory syncytial virus infections in pediatric transplant recipients: A Canadian Paediatric Surveillance Program study

The incidence and spectrum of severity of RSV infections in SOT or HSCT recipients is not known. From September 2010 through August 2013, pediatricians were surveyed monthly by the CPSP for SOT or HSCT recipients with RSV infection within two yr post‐transplant. There were 24 completed case report forms that fit the inclusion criteria (10 HSCT and 14 SOT recipients). Six of 24 cases (25%) remained outpatients, and 11 (46%) were managed on an inpatient ward, while seven (29%) required intensive care of which five required mechanical ventilation and two died of RSV infection. Ten of 23 cases (43%) were nosocomial with these data not recorded for one case. Many transplant recipients recover uneventfully from RSV infection in the first two yr post‐transplant. However, severe disease and death also occur. Larger studies are required to establish risk factors for poor outcomes. Prevention of nosocomial RSV should be a priority in transplant recipients.