Paediatric lver transplantation for children treated at public health facilities in South Africa: Time for change

Paediatric liver transplantation (PLT) is the only therapeutic option for many children with end-stage chronic liver disease or irreversible fulminant hepatic failure and is routinely considered as a therapy by paediatric gastroenterologists and surgeons working in developed countries. In South Africa (SA), a PLT programme is available at Red Cross War Memorial Children’s Hospital in Cape Town since November 1991, and another has rapidly developed at the Wits Donald Gordon Medical Centre in Johannesburg over the past decade. However, for most children with progressive chronic liver disease who are reliant on the services provided at public health facilities in SA, PLT is not an option because of a lack of resources in a mismanaged public health system. This article briefly outlines the services offered at Chris Hani Baragwanath Academic Hospital - which is typical of public health facilities in SA - and proposes that resources be allocated to establish an innovative, nationally funded centre that would enable greater numbers of children access to a PLT programme

Combined paediatric liver-kidney transplantation: Analysis of our experience and literature review

Background. Renal insufficiency is increasingly common in end-stage liver disease and allocation of livers to this category of patient has escalated. The frequency of combined liver-kidney transplantation (CLKT) has consequently increased. Indications for CLKT in children differ from those for adults and typically include rare congenital conditions; subsequently limited numbers of this procedure have been performed in paediatric patients worldwide. Scant literature exists on the subject. Methods. Subsequent to institutional approval, a retrospective chart analysis of all paediatric CLKTs performed at the Transplant Unit, Wits Donald Gordon Medical Centre, University of the Witwatersrand, Johannesburg, South Africa between January 2005 and July 2013 was conducted. Results. Defining children as younger than 18 years of age, 43 patients had received a liver transplant since 2005, of whom 8 received a CLKT. Indications included autosomal recessive polycystic kidney disease (n=3), primary hyperoxaluria type 1 (n=4) and heterozygous factor H deficiency with atypical haemolytic uraemic syndrome (n=1). Graft combinations included whole liver and one kidney (n=5), whole liver and two kidneys (n=1) and left lateral liver segment and one kidney (n=2), all from deceased donors. Patient age ranged from 4 to 17 years (median 9) and included 4 females and 4 males. Weight ranged from 13 to 42 kg (median 22.5). We describe one in-hospital mortality. The remaining 7 patients were long-term survivors with a survival range from 6 to 65 months. Conclusions. Although rarely indicated in children, CLKT is an effective treatment option, appropriately utilising a scarce resource and significantly improving quality of life in the recipient.

Favourable outcomes for the first 10 years of kidney and pancreas transplantation at Wits Donald Gordon Medical Centre, Johannesburg, South Africa

Background. It is important for centres participating in transplantation in South Africa (SA) to audit their outcomes. Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, SA, opened a transplant unit in 2004. The first 10 years of kidney and pancreas transplantation were reviewed to determine outcomes in respect of recipient and graft survival.Methods. A retrospective review was conducted of all kidney-alone and simultaneous kidney-pancreas (SKP) transplants performed at WDGMC from 1 January 2004 to 31 December 2013, with follow-up to 31 December 2014 to ensure at least 1 year of survival data. Information was accessed using the transplant registers and clinical records in the transplant clinic at WDGMC. The Kaplan-Meier method was used to estimate 1-, 5- and 10-year recipient and graft survival rates for primary (first graft) kidney-alone and SKP transplants.Results. The overall 10-year recipient and graft survival rates were 80.4% and 66.8%, respectively, for kidney-alone transplantation. In the kidney-alone group, children tended towards better recipient and graft survival compared with adults, but this was not statistically significant. In adults, recipient survival was significantly better for living than deceased donor type. Recipient and graft survival were significantly lower in black Africans than in the white (largest proportion in the sample) reference group. For SKP transplants, the 10-year recipient survival rate was 84.7%, while kidney and pancreas graft survival rates were 73.1% and 43.2%, respectively.Conclusion. Outcomes of the first 10 years of kidney and pancreas transplantation at WDGMC compare favourably with local and international survival data

Humid tropical rain forest has expanded into eucalypt forest and savanna over the last 50 years

Tropical rain forest expansion and savanna woody vegetation thickening appear to be a global trend, but there remains uncertainty about whether there is a common set of global drivers. Using geographic information techniques, we analyzed aerial photography of five areas in the humid tropics of northeastern Queensland, Australia, taken in the 1950s and 2008, to determine if changes in rain forest extent match those reported for the Australian monsoon tropics using similar techniques. Mapping of the 1950s aerial photography showed that of the combined study area (64,430 ha), 63% was classified as eucalypt forests/woodland and 37% as rain forest. Our mapping revealed that although most boundaries remained stable, there was a net increase of 732 ha of the original rain forest area over the study period, and negligible conversion of rain forest to eucalypt forest/woodland. Statistical modeling, controlling for spatial autocorrelation, indicated distance from preexisting rain forest as the strongest determinant of rain forest expansion. Margin extension had a mean rate across the five sites of 0.6 m per decade. Expansion was greater in tall open forest types but also occurred in shorter, more flammable woodland vegetation types. No correlations were detected with other local variables (aspect, elevation, geology, topography, drainage). Using a geographically weighted mean rate of rain forest margin extension across the whole region, we predict that over 25% of tall open forest (a forest type of high conservation significance) would still remain after 2000 years of rain forest expansion. This slow replacement is due to the convoluted nature of the rain forest boundary and the irregular shape of the tall open forest patches. Our analyses point to the increased concentration of atmospheric CO2 as the most likely global driver of indiscriminate rain forest expansion occurring in northeastern Australia, by increasing tree growth and thereby overriding the effects of fire disturbance

Metabolic Trajectories Following Contrasting Prudent and Western Diets from Food Provisions: Identifying Robust Biomarkers of Short-Term Changes in Habitual Diet

A large body of evidence has linked unhealthy eating with an alarming increase in obesity and chronic disease worldwide. However, existing methods of assessing dietary intake rely on food frequency questionnaires or dietary records that are prone to bias and selective reporting. Herein, metabolic phenotyping was performed on 42 healthy participants from the Diet and Gene Intervention (DIGEST) pilot study, a parallel two-arm randomized clinical trial that provided complete diets to all participants. Matching urine and plasma specimens were collected at baseline and following 2 weeks of provision of either a Prudent or Western diet with a weight-maintaining menu plan designed by a dietician. Targeted and nontargeted metabolite profiling was conducted using three complementary analytical platforms, where 80 serum metabolites and 84 creatinine-normalized urinary metabolites were reliably measured (CV 75%) after implementing a rigorous data workflow for metabolite authentication with stringent quality control. We classified a panel of metabolites with distinctive trajectories following 2 weeks of food provisions when using complementary univariate and multivariate statistical models. Unknown metabolites associated with contrasting dietary patterns were identified with high resolution MS/MS and/or co-elution after spiking with authentic standards. Overall, 3-methylhistidine and proline betaine concentrations increased consistently when participants were assigned a Prudent diet (q ± 0.30, p < 0.05) to changes in average intake of specific nutrients from self-reported diet records reflecting good adherence to food provisions. This study revealed robust biomarkers sensitive to short-term changes in habitual diet that can be used to reliably monitor healthy eating patterns for new advances in nutritional epidemiology, as well as the design of evidence-based public health policies for chronic disease prevention

Living donor liver transplant from an HIV-positive mother to her HIV-negative child : opening up new therapeutic options

OBJECTIVE : Transplant a liver from an HIV-positive mother to her HIV-negative child to save the child’s life. DESIGN : A unique case of living donor liver transplantation from an HIV-positive mother to her HIV-negative child in South Africa. Two aspects of this case are ground-breaking. First, it involves living donation by someone who is HIVpositive and second it involves controlled transplant of an organ from an HIV-positive donor into an HIV-negative recipient, with the potential to prevent infection in the recipient. METHODS : Standard surgical procedure for living donor liver transplantation at our centre was followed. HIV-prophylaxis was administered preoperatively. Extensive, ultrasensitive HIV testing, over and above standard diagnostic assays, was undertaken to investigate recipient serostatus and is ongoing. RESULTS : Both mother and child are well, over 1 year posttransplantation. HIV seroconversion in our recipient was detected with serological testing at day 43 posttransplant. However, a decline in HIV antibody titres approaching undetectable levels is now being observed. No plasma, or cell-associated HIV-1 DNA has been detected in the recipient at any time-point since transplant. CONCLUSION : This case potentially opens up a new living liver donor pool which might have clinical relevance in countries where there is a high burden of HIV and a limited number of deceased donor organs or limited access to transplantation. However, our recipient’s HIV status is equivocal at present and additional investigation regarding seroconversion events in this unique profile is ongoing.The South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa.http://journals.lww.com/aidsonlineam2019Medical Virolog

Carpal tunnel syndrome and the "double crush" hypothesis: a review and implications for chiropractic

Upton and McComas claimed that most patients with carpal tunnel syndrome not only have compressive lesions at the wrist, but also show evidence of damage to cervical nerve roots. This "double crush" hypothesis has gained some popularity among chiropractors because it seems to provide a rationale for adjusting the cervical spine in treating carpal tunnel syndrome. Here I examine use of the concept by chiropractors, summarize findings from the literature, and critique several studies aimed at supporting or refuting the hypothesis. Although the hypothesis also has been applied to nerve compressions other than those leading to carpal tunnel syndrome, this discussion mainly examines the original application – "double crush" involving both cervical spinal nerve roots and the carpal tunnel. I consider several categories: experiments to create double crush syndrome in animals, case reports, literature reviews, and alternatives to the original hypothesis. A significant percentage of patients with carpal tunnel syndrome also have neck pain or cervical nerve root compression, but the relationship has not been definitively explained. The original hypothesis remains controversial and is probably not valid, at least for sensory disturbances, in carpal tunnel syndrome. However, even if the original hypothesis is importantly flawed, evaluation of multiple sites still may be valuable. The chiropractic profession should develop theoretical models to relate cervical dysfunction to carpal tunnel syndrome, and might incorporate some alternatives to the original hypothesis. I intend this review as a starting point for practitioners, educators, and students wishing to advance chiropractic concepts in this area

Paediatric liver transplantation in Johannesburg revisited: 59 transplants and challenges met

Background. A paediatric liver transplant programme was started at the Wits Donald Gordon Medical Centre, Johannesburg, South Africa (SA), in November 2005. We reported on the first 29 patients in 2012. Since then we have performed a further 30 transplants in 28 patients, having met the major challenge of donor shortage by introducing a living related donor programme and increasing the use of split liver grafts.Objective. To review the Wits Donald Gordon Medical Centre paediatric liver transplant programme to date. We describe how the programme has evolved and specifically compare the outcomes of the first cohort with the most recent 28 patients.Methods. Case notes of all paediatric liver transplants performed between 14 November 2005 and 30 June 2014 were retrospectively reviewed. Data were analysed for age and weight at transplantation, indication and type of graft. Morbidity and mortality were documented, specifically biliary and vascular complications. Comparison was made between Era 1 (November 2005 - October 2012) and Era 2 (November 2012 - June 2014).Results. A total of 59 transplants were performed in 57 patients. Age at transplantation ranged from 9 months to 213 months (mean 82.39 months) and weight ranged from 5 kg to 62 kg (mean 21 kg). A total of 23 whole livers, 10 reduced-size grafts, 14 split liver grafts and 12 living donor liver transplants (LDLTs) were performed. Eight patients were referred with fulminant hepatic failure (FHF), all in Era 2. Of these, three patients were successfully transplanted. Of the 57 patients, 45 are alive and well with actuarial 1-year patient and graft survival of 85% and 84%  and 5-year patient and graft survival of 78% and 74%, respectively. Sixteen (25.42%) biliary complications occurred in 15 of our 59 transplants. Seven patients developed significant vascular complications. Comparing Era 1 with Era 2, mean age at transplant decreased from 100.86 months to 64.73 months, mean weight from 25.2 kg to 16.9 kg, and type of graft utilised changed with a trend away from the use of whole livers and reduced-sized grafts to split livers and segment 2,3 LDLT grafts.Conclusion. Initially limited by a shortage of donor organs, we aggressively explored optimal utilisation, splitting liver grafts from deceased donors as often as possible and establishing an LDLT programme. This increased access to donor livers allowed us to include patients with FHF and to perform retransplantation in recipients with early graft failure. It remains to offer liver transplantation to the entire paediatric community in SA, in conjunction with the only other established paediatric liver transplant unit, at Red Cross War Memorial Children’s Hospital in Cape Town