Living-Related Versus Deceased Donor Pediatric Liver Transplantation: A Multivariate Analysis of Technical and Immunological Complications in 235 Recipients

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.     

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.     

低龄婴儿双供肾移植给成人22例报道

目的总结单中心低龄婴儿双供肾移植给成人的临床效果。方法回顾性纳入2013年7月至2017年10月华中科技大学同济医学院附属同济医院实施的所有儿童双供肾移植给成人受者共22例临床资料和随访数据。22例供者年龄(2.9±1.7)个月,体重(4.9±1.4)kg,其中15例小于3月龄。受者多为低体重女性成人,体重(46.3±5.6)kg。总结早期移植失败及随访期间移植肾失功或受者死亡原因。根据是否发生单侧移植肾血栓,移植肾功能恢复者又进一步分为双肾存活组和单肾存活组,比较移植肾中-长期功能。结果4例受者在术后早期出现移植失败,包括双肾血栓2例、移植肾破裂切除1例和受者多器官功能衰竭死亡1例。18例受者移植肾功能恢复出院,随访期间因移植肾新生肿瘤切除双肾1例、因复杂全身原因死亡1例、因间质性肺炎死亡1例,余15例受者双肾均存活者10例(中位随访59个月),单肾存活者5例(中位随访48个月)。移植1年时双肾存活组估算肾小球滤过率为(95±27)ml/(min·1.73 m2),显著高于单肾存活组(61±24)ml/(min·1.73 m2)(P<0.05),但3年时分别为(95±21)ml/(min·1.73 m2)和(69±31)ml/(min·1.73 m2),差异缩小,差异无显著统计学意义(P=0.12)。结论低龄婴儿双供肾移植虽然可以扩大供肾来源,但发生早期移植失败和单肾栓塞的风险较高。在单肾存活的情况下,受者仍具有相对满意的中-长期移植效果。     

Hepatitis E antibodies in Egyptian adolescent females: their prevalence and possible relevance

Hepatitis E virus has been implicated as a frequent cause of acute sporadic hepatitis among Egyptian children. Moreover, an extraordinarily high seroprevalence rate was previously reported in a semiurban Nile Delta population. A conspicuous feature of hepatitis E is the high morbidity and mortality it can cause among infected pregnant women. We therefore evaluated the prevalence of HEV antibodies in adolescent females using a solid-phase enzyme linked immunoassay based on two recombinant hepatitis E virus antigens. A high prevalence rate (38.9%) was found in 95 apparently healthy adolescent females. The mean age of the study subjects was 21.81 +/- 2.5 (SD) range 16-25 years. Eighty (84.2%) subjects resided in Alexandria, while 15 (15.8%) came from semiurban villages of Alexandria Governorate. An increased prevalence was noted with age, as anti-HEV antibodies were detected in 32.1% and 41.8% of study participants in the second and third decades of life, respectively. Similarly, those illiterate or having received less than primary education exhibited a higher HEV prevalence than those with higher education (46.3% vs 29.3%). The majority of subjects having serological evidence of HEV infection denied previous history of jaundice which shows that HEV infection was subclinical in those cases. Ten (55.6%) pregnant females participating in the study, as well as 48 (62.3%) non pregnant females lacked serological evidence of HEV infection; i.e., 60.01% (10 + 48 out of 95) of women in the childbearing age may be susceptible to infection. This report suggests that HEV is endemic in Alexandria, Egypt; the epidemiologic risk factors associated with HEV infection need further exploration.     

A prospective randomised comparative study of endoscopic band ligation versus injection sclerotherapy of bleeding internal haemorrhoids in patients with liver cirrhosis

Background and study aimsBleeding internal haemorrhoids are common and used to be treated surgically with too many complications. Endoscopic therapy is trying to take the lead. Sclerotherapy and rubber band ligation are the candidates to replace surgical therapy especially in patients with liver cirrhosis. The aim of this study was to compare endoscopic injection sclerotherapy (EIS) to endoscopic rubber band ligation (EBL) regarding effectiveness and complications in the treatment of bleeding internal haemorrhoids in Egyptian patients with liver cirrhosis.Patients and methodsOne hundred and twenty adult patients with liver cirrhosis and bleeding internal haemorrhoids were randomised into two equal groups; the first treated with EBL using Saeed multiband ligator, and the second with EIS using either ethanolamine oleate 5% or N-butyl cyanoacrylate. All groups were matched as regards age, sex, Child score and pre-procedure Doppler values. Patients were followed up clinically and with abdominal ultrasound/Doppler for 6 months. Endoscopic and endosonography/Doppler was done before and one month after the procedure. Pre and post-procedure data were recorded and analysed.ResultsBoth techniques were highly effective in the control of bleeding from internal haemorrhoids with a low rebleeding [10% in the EBL group and 13.33% in the EIS group] and recurrence [20% in the EBL group 20% in the EIS group] rates. Child score had a positive correlation with rebleeding and recurrence in EIS group only.Pain score and need for analgesia were significantly higher while patient satisfaction was significantly lower in EIS compared to EBL [p < 0.05]. No significant difference between ethanolamine and cyanoacrylate subgroups was found [p > 0.05].ConclusionsBoth EBL and EIS were effective in the treatment of bleeding internal haemorrhoids in patients with liver cirrhosis. EBL had significantly less pain and higher patient satisfaction than EIS. EBL was also safer in patients with advanced cirrhosis.     

Real Time Three‐Dimensional Echocardiography for Quantification of Ventricular Volumes,Mass, and Function in Children with Congenital and Acquired Heart Diseases

Quantitative measurement of left ventricular (LV) volumes, mass, and function is one of the most common and important indications for echocardiography. These measurements are among the most powerful tools for diagnosis and prognosis of congenital and acquired heart diseases and for assessment of medical, percutaneous, and surgical interventions. Awareness is also growing of the importance of right ventricular (RV) volume, mass, and function in many cardiopulmonary diseases. Furthermore, there are challenges and opportunities to measure the volume, mass, and function of complex chambers such as the left atrium, right atrium, and the univentricular heart. As echocardiography continues to be the imaging modality of choice for these measurements, the strengths and limitations of M‐mode, two‐dimensional (2D), and recently three‐dimensional (3D) echocardiographic (3DE) methodologies for accurate and reproducible measurement of these indices have been extensively investigated for congenital and acquired heart diseases. Evidence suggests that 3DE provides improved accuracy and reproducibility over 2D methods for measurement of LV volume and function calculation in adults and in children. Data have accumulated on the utility of 3DE for measuring chamber volumes and function for the RV and for the single ventricle, which may become more widely used in clinical and research arenas in the future. Finally, new advanced modes of analysis such as 3D strain and synchrony analysis by 3DE are promising methodologies that warrant further investigation.     

LC-ESI-MS/MS reveals the formation of reactive intermediates in brigatinib metabolism: elucidation of bioactivation pathways

Brigatinib (BGB) is a newly approved anaplastic lymphoma kinase (ALK) inhibitor. On April 28, 2017, BGB was approved by the U.S. FDA for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. The toxicity profile of BGB includes nausea, fatigue, diarrhea, elevated lipase, dyspnoea, hypertension, hypoxia, pneumonia, elevated amylase, pulmonary embolism, elevated ALT, hyponatraemia and hypophosphatemia. Using LC-MS/MS, we investigated the in vitro phase I metabolism of for BGB in rat liver microsomes (RLMs). In the in vitro metabolism of BGB, iminium reactive intermediates were trapped by potassium cyanide forming a stable complex that can be characterized by LC-MS/MS. Four BGB in vitro phase I metabolites were identified. In vitro phase I metabolic pathways were N-dealkylation, α hydroxylation and α oxidation. Additionally, three iminium reactive metabolites were found and the bioactivation mechanisms were proposed. A piperidine ring was found to be responsible for BGB bioactivation. The presence of these three reactive metabolites may be the main reason for BGB side effects. A literature review showed no previous article reported the in vitro phase I metabolism study of BGB or structural identification of the formed reactive metabolites.

Four phase I BGB metabolites and three cyano adducts for BGB were detected using LC-MS/MS. The piperidine ring was found to be responsible for BGB bioactivation and the bioactivation pathways are proposed.