Renal transplant recipient and deceased-donor risk profiles at Wits Donald Gordon Medical Centre, Johannesburg, South Africa: A 9-year review.

BACKGROUND: Renal transplantation is the gold-standard therapy for end-stage renal disease. Decision-making around the acceptance of deceased-donor organs is complex and time sensitive. Risk scoring systems for both donors and recipients attempt to simplify the allocation of renal grafts to the most appropriate recipient. OBJECTIVES: To investigate the role of these transplant risk scores in the South African (SA) setting. METHODS: A total of 188 adult deceased-donor organ referrals over the 9-year period 1 January 2013 - 31 December 2021 were included. The Kidney Donor Risk Index (KDRI) and the UK KDRI were calculated for each donor. Recipients who were allocated these grafts were characterised, and the Hennepin Transplant Risk Score and the Kidney Transplant Morbidity Index (KTMI) were calculated. RESULTS: The median (interquartile range) KDRI was 1.2 (0.9 - 1.6), confirming that low- to average-risk donors were being utilised. Similarly, the median UK KDRI was 0.9 (0.8 - 1.2). Both these scores performed poorly in predicting graft and patient survival, with a C-statistic of 0.5. Renal recipient risk scores also demonstrated low- to average-risk patients being transplanted, with a median Hennepin score of 2 - 4 points and a KTMI of 2 points. These recipient scores predict increased recipient mortality at high scores, albeit with low sensitivity, and were not significantly associated with graft survival. CONCLUSION: Deceased-donor and renal recipient risk scores commonly used internationally performed poorly in predicting graft survival in our cohort, and should be used with caution in the SA setting. A conservative approach to organ donor referral and utilisation as well as renal transplant recipient listing was noted.

A retrospective analysis of outcomes and complications of living- and deceased-donor split-liver transplantation in Johannesburg, South Africa.

BACKGROUND: South African transplant centres are faced with significant challenges in meeting the need for liver transplantation, owing to the low and ever-decreasing number of deceased-donor organs. To increase organ utility, deceased-donor split-liver transplant (DDSLT) and living-donor liver transplant (LDLT) programmes were initiated in the Wits Transplant Unit. OBJECTIVE: To evaluate outcomes of the LDLT and DDSLT programmes. METHODS: A retrospective analysis of de-identified recipient and donor variables from all adult and paediatric DDSLTs and LDLTs conducted between 2013 and 2021 was performed. Comparison of categorical study variables between graft types was done with the χ2 test. Continuous variables were compared by means of the independent samples t-test. Cox proportional hazards regression was performed to examine the effect of graft type on recipient and graft survival. All comparisons were made unadjusted, and adjusted for recipient age, recipient ethnicity, donor sex, and graft-weight-to-recipient-weight ratio (GWRWR) (for the paediatric cohort); and for donor age and GWRWR (for the adult cohort). RESULTS: A total of 181 paediatric and 48 adult liver transplants have been performed since the inception of the two programmes. Chronic liver failure, specifically intra- and extrahepatic cholestatic disease, was our main indication for liver transplantation in both cohorts. There were no significant differences between the DDSLTs and LDLTs in respect of pre- or post-discharge intervention, in-hospital mortality, length of stay, and recipient or graft survival within both the paediatric and adult groups. Our overall 1- and 3-year survival estimates (95% confidence intervals) were 77% (70% - 83%) and 71% (64% - 78%) for the paediatric cohort, and 77% (62% - 87%) and 66% (50% - 78%) for the adult cohort, respectively. CONCLUSION: The results of this study demonstrate comparable outcomes between DDSLT and LDLT, indicating that both methods are effective approaches to optimise organ utilisation for liver transplantation within our setting.

ABO-incompatible liver transplantation - exploring utilitarian solutions to restricted access and organ shortages: A single-centre experience from Johannesburg, South Africa.

BACKGROUND: Liver transplantation is the definitive management for severe acute liver failure refractory to supportive management, and end- stage chronic liver failure. Owing to a shortage of deceased liver donors, South Africa requires innovative techniques to broaden the donor pool. OBJECTIVES: This study evaluated the outcomes of the Wits Transplant Unit ABO-incompatible liver transplant (ABOi-LT) programme. METHODS: This retrospective record review compared all adult and paediatric patients receiving ABO-compatible (ABOc) and ABO-incompatible (ABOi) liver transplants from January 2014 to December 2021 with a minimum one-year follow-up. Primary outcomes were recipient and graft survival and secondary outcomes included vascular, enteric and biliary complications, relook surgery, acute cellular rejection (ACR) and lenghth of hospital stay. Cox proportional hazards regression was performed to examine the effect of ABO-compatibility group on recipient and graft survival. The relationship between the ABO-compatibility group and categorical outcomes was assessed by binomial regression. RESULTS: During the study period, 532 liver transplants were performed; 44/532 (8%) were ABOi of which 14/44 (32%) were paediatric and 30/44 (68%) adult recipients. Within the pediatric group, the proportion of transplants performed for acute liver failure was significantly higher in the ABOi group (7/14; 50%) compared with the ABOc group (33/207; 16%) (p=0.005). Comparable recipient and graft survival estimates were noted: one-, three- and five-year recipient survival in the ABOi group was 77% (95% confidence interval (CI) 44 - 92), 58% (95% CI 17 - 84) and 58% (95% CI 17 - 84) respectively. There were significantly increased relative risks of relook surgery for the ABOi group compared with the ABOc group, both overall (relative risk (RR) 1.74; 95% CI 1.10 - 2.75) and at 90 days (RR 2.28; 95% CI 1.27 - 4.11); and also, for pre-discharge bloodstream infection (BSI), (RR 1.84; 95% CI 1.11 - 3.06). In adults, there were significantly more acute indications for liver transplantation in the ABOi (10/30; 33%) compared with the ABOc group (26/281; 9%) (p=0.0007) with the most common cause being drug or toxin ingestion (16/36; 44%). For the ABOi group, recipient survival estimates (95% CI) at 1, 3 and 5 years were 71% (50 - 84), 63% (41 - 78) and 58% (37 - 75) which, as noted with complication rates, were similar between ABO groups. CONCLUSION: This study confirms ABOi-LT as a feasible option to increase the liver donor pool in this organ-depleted setting as recipient survival and complication rates were similar between ABO-compatibility groups.

Wits Transplant Unit Annual Report 2022: Adult and paediatric liver transplantation.

In 2022, the Wits Transplant Unit performed 57 liver transplants: 33/57 adult (58%) and 24/57 paediatric (42%) recipients. At the beginning of 2022, 28 candidates were on the adult waitlist. Forty-six candidates were added to the waitlist during the year. Sixty-five percent of waitlisted candidate were transplanted. Adult candidates remained on the waitlist for longer than previous years, with 52% of them waitlisted for less than one year before undergoing liver transplantation. There was a decrease in adult pretransplant mortality to 9% in 2021 from 25% in 2020. The most common aetiology in waitlist candidates was alcoholic steatohepatitis (ASH)/non-alcoholic steatohepatitis (NASH) (36%) and in recipients cholestatic (primary sclerosing cholangitis (PSC) and primary biliary sclerosis (PBC)) (40%). Most adult recipients received a deceased donor graft (79%). Unadjusted recipient one- and three-year survivals were 75% (95% confidence interval (CI) 65 - 83) and 74% (95% CI 65 - 81), respectively. In the paediatric population, the most common aetiologies for both pretransplant candidates and transplant recipients remained cholestatic disease and acute liver failure. There was a decrease in paediatric pretransplant mortality from 27% in 2017 to 6% in 2021. Unlike the adult cohort, most paediatric recipients received a living donor graft (79%). Unadjusted one-year and three-year survival rates were 85% (95% CI 75 - 92) and 68% (95% CI 56 - 77), respectively.

The paediatric liver transplant experience in Johannesburg, South Africa: A broad overview and update.

BACKGROUND: The Wits Transplant Unit performed its first paediatric liver transplant in 2005. Initial experiences from the unit were published in 2012 and 2014. Since then, significant progress has been made in capacity-building the unit, improving outcomes and enhancing service delivery. This paper presents a broad overview and update of the unit's 17-year experience.   Methods: We conducted a retrospective review of all paediatric liver transplants performed in Johannesburg from 1 January 2005 to 31 December 2021 with a minimum one-year follow-up. Data were accessed from the Wits Donald Gordon Medical Centre Paediatric Liver Transplant Research Database (University of the Witwatersrand Human Research Ethics approval: M190749). The following data were collected: donor and recipient sociodemographic and clinical characteristics, details of transplant procedures, donor grafts and recipient outcomes (post-operative complications, graft and recipient survival).   Results: A total of 270 transplants were performed during the review period. Two thirds of recipients (n=180, 67%) were younger than 5 years at time of transplant and half (n=135, 50%) received a living donor graft. The most common indication for liver transplant was biliary atresia, followed by acute liver failure. Unadjusted recipient survival was 80% (95% CI: 75-85%) at one year, and 68% (95% CI: 59-75%) at five years. Waiting list mortality decreased from 27.3% in 2017 to 5.9% in 2021. One hundred and fifty-four (57.0%) recipients experienced at least one type of intervention requiring surgical complication - the most common being biliary in nature (n = 91; 33.7%).   Conclusion: Over last seventeen years, a sustainable paediatric liver transplantation service has been established in Johannesburg. Living donor, split and ABO incompatible liver transplants have been incorporated in response to the severe organ shortage in South Africa. However, our outcomes can be improved. Additionally, a national transplant initiative to coordinate timeous referrals and expand access to liver transplantation for children with severe acute and chronic liver failure is advised.

The novel application and effect of an ultraviolet light decontamination strategy on the healthcare acquisition of carbapenem-resistant Enterobacterales in a hospital setting.

BACKGROUND: The role of the hospital environment as contributory to healthcare acquisition of multidrug-resistant organisms (MDROs) is increasingly recognized. Ultraviolet light decontamination can minimize the environmental bioburden, thereby potentially reducing healthcare acquisition. This effect has been demonstrated for typical environmental MDROs, e.g. meticillin-resistant Staphylococcus aureus, vancomycin-resistant entero-cocci, and Clostridioides difficile; however, its role in reducing carbapenem-resistant Enterobacterales (CRE) incidence rates is unclear. AIM: To evaluate the impact of continuous ultraviolet light (C-UV) on healthcare acquisition rates of CRE. METHODS: A 26-month pragmatic, prospective interventional study with addition of C-UV decontamination to standard cleaning was conducted in units at high risk for CRE acquisition. Introduction of C-UV followed a 12 month baseline period, with a two-month wash-in period. Implementation included terminal decontamination at discharge and a novel in-use protocol, whereby rooms occupied for ≥48 h were decontaminated during the course of the patients' in-hospital stay. Incidence density rates of CRE during the intervention period were compared to the baseline period using interrupted time series regression. Rates were adjusted for ward/admission prevalence and analysed according to C-UV protocol. FINDINGS: The in-use C-UV protocol demonstrated a significant negative association with the incidence density rate of CRE when adjusting for CRE admission rate (P = 0.0069). CRE incidence density rates decreased significantly during the intervention period (P = 0.042). Non-intervention units demonstrated no change in incidence density rates when adjusting for ward and/or admission prevalence. CONCLUSION: C-UV decontamination can potentially reduce healthcare acquisition of CRE when implemented with an in-use protocol.

Burn-injured patients - the preferably unheard.

BACKGROUND: Data on colorectal cancer (CRC) diagnosis to treatment interval (DTI), an index of quality assurance in high-income countries (HICs) is lacking in South Africa. This study aimed to determine DTIs and their impact on CRC survival in a South African cohort. METHODS: Participants (n = 289) from the Colorectal Cancer in South Africa (CRCSA) cohort were identified for inclusion. The DTI was defined as the duration between the diagnosis and initial definitive treatment and categorised into approximate quartiles (Q1-4). The DTI quartiles were 0-14 days, 15-28 days, 29-70 days, and ≥ 71 days. Overall survival (OS) was illustrated using the Kaplan-Meier method and compared between DTI groups using Cox proportional hazards (PH) regression. RESULTS: There was no significant impact of the DTI (as quartiles) on overall CRC survival. The median length of time between DTI in this cohort was 29 days. Significant associations were identified between the DTI and self-reported ethnicity (p-value = 0.025), the site of the malignancy (colon vs rectum) (p-value < 0.0001), multidisciplinary team (MDT) review (p-value = 0.015) and the initial treatment modality (p-value < 0.0001). CONCLUSION: Prolonged DTIs did not significantly impact survival for those with CRC in the CRCSA cohort. Symptom to diagnosis time should be investigated as a determinant of survival.

Laboratory parameters associated with prolonged hospital length of stay in COVID-19 patients in Johannesburg, South Africa.

BACKGROUND: Coronavirus disease (COVID-19) has imposed unprecedented stressors on South Africa (SA)'s healthcare system. Superimposed on the country's quadruple burden of disease, pandemic-related care further exposes existing inequities. Some of these inequities are specific to hospital-based inpatient services, such as the geographical maldistribution of hospital beds, lack of oxygen supplies and assisted ventilation, and scarcity of trained healthcare workers. Certain high-risk groups, such as individuals with cardiometabolic comorbidity, are likely to develop severe COVID-19 disease requiring hospitalisation with potential for a prolonged length of stay (LoS). It may be helpful for health authorities to identify those at risk for prolonged LoS to facilitate appropriate health systems planning. OBJECTIVES: To identify hospital admission laboratory parameters associated with a hospital stay >14 days in patients with COVID-19 pneumonia. METHODS: A retrospective observational study design was used. Laboratory data were obtained from an SA private laboratory for 642 inpatients with suspected or confirmed COVID-19 pneumonia, comprising 7 months of admission laboratory data from six private hospitals in Johannesburg, Gauteng Province. RESULTS: Of 642 hospital admissions for pneumonia, 497 were confirmed to have COVID-19 infection (reverse transcription-polymerase chain reaction test positive). In the COVID-19-positive group, hospital LoS was prolonged in 35.4% of admissions. Univariate analysis demonstrated an association with the following risk factors for prolonged LoS: older age; male sex; high serum creatinine, sodium (Na), chloride, potassium and urea levels and low estimated glomerular filtration rate; raised white blood cell count, lymphopenia, neutrophilia and an elevated neutrophil-to-lymphocyte ratio (NLR); and elevated levels of D-dimers, interleukin-6 (IL-6), and procalcitonin (PCT). The strongest univariate associations (relative risk (RR) ≥2.0) with a hospital stay >14 days were high Na levels, NRL >18, high PCT levels and IL-6 >40 pg/mL. On multivariable analysis, the following factors remained significantly associated with prolonged LoS: older age (RR 1.015 per year of age; 95% confidence interval (CI) 1.005 - 1.024); hypernatraemia (RR 1.80; 95% CI 1.25 - 2.60); hyperkalaemia (RR 1.61; 95% CI 1.18 - 2.20); and neutrophilia (RR 1.47; 95% CI 1.15 - 1.88). CONCLUSIONS: COVID-19 pandemic preparedness requires hospital-based inpatient care to be prioritised in resource-limited settings, and availability of beds and prompt admissions are essential to ensure good clinical outcomes. In this study of COVID-19 patients admitted with pneumonia, multivariable analysis showed older age, hypernatraemia, hyperkalaemia and neutrophilia to be associated with LoS >14 days. This may assist with healthcare systems planning.

Colorectal cancer liver metastases: management and five-year survival in a South African patient cohort.

BACKGROUND: Approximately 25% of patients with colorectal cancer (CRC) will be diagnosed with CRC liver metastases (CRCLM) during the course of their disease. No data regarding CRCLM presentation, management and survival outcomes has been published from either the private or public health care sectors in South Africa. This study aimed to address this deficit, reporting on a private sector cohort. METHODS: A retrospective review of a private health care funder's database from 1 January 2008 to 31 December 2015 was performed. ICD-10 diagnosis codes were used to identify CRC and CRCLM. Procedure codes assigned to hospital admissions were used to identify the type of surgical treatment. Chemotherapy was identified by the WHO Anatomical Therapeutic Chemical classification system of medicines. Treatment patterns were assessed and five-year overall survival (OS) was calculated. Survival was estimated using the Kaplan-Meier method, and Cox proportional-hazards regression was used for between group survival comparisons. RESULTS: Six hundred and one (601) of 3 412 patients presenting with CRC (17.6%) were diagnosed with CRCLM at presentation or during the follow-up period. Sixty patients with CRCLM (10.0%) underwent resection of the primary CRC and liver resection for metastases, 281 (46.8%) underwent CRC resection only, 180 (30%) received chemotherapy only, and 47 (7.8%) received no treatment. Five-year OS for these groups were 57.3%, 15.6%, 9.8% and 0% respectively. CONCLUSION: Five-year OS of the various CRCLM treatment pathways in a South African private sector population compares to results published in international series. However, a smaller proportion of patients with CRCLM underwent liver resection, compared to international studies.

Lymphopenia and IgG2 subclass deficiency in patients with severe COVID-19 pneumonia.

BACKGROUND: COVID-19 caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) manifests with a range of disease severities. A small proportion of COVID-19 patients are severely ill; however, a significant proportion of these patients are critically ill, and require admission and mechanical ventilation, which is associated with a high mortality. OBJECTIVE: To identify factors that may predispose patients with COVID-19 to severe disease that requires mechanical ventilation (MV). METHODS: We performed a retrospective audit of patients admitted with COVID-19 pneumonia to the intensive care unit (ICU) and medical wards to evaluate the potential associations between comorbid conditions, lymphopenia and IgG subclass deficiency with a need for MV. RESULTS: A total of 51 patients were included in the study. Almost half of the patients (47%; n=24) were documented to have IgG2 deficiency, 43% (n=22) had lymphopenia and 37% (n=19) had combined lymphopenia and IgG2 subclass deficiency. Of the 24 patients who required MV, 75% had IgG2 subclass deficiency, 73% had lymphopenia and 50% had both. The relative risk for requiring MV was 2.64, 3.38 and 2.81 for lymphopenia, IgG2 subclass deficiency and both, respectively. CONCLUSION: These findings suggest that lymphopenia, low IgG2 concentrations or the combination of both may be used to identify patients with severe COVID-19 that are at increased risk for MV. This may facilitate earlier identification of patients at high risk, who may benefit from more intensive therapy.

Vitamin D levels in patients admitted to the intensive care unit and the association with organ dysfunction and glutamine levels.

BACKGROUND: Vitamin D deficiency is common in intensive care unit (ICU) patients (50 - 82%) and is associated with multi-organ dysfunction. Vitamin D deficiency alters pathways of glutamine metabolism in critical illness, but the impact of vitamin D status on glutamine levels is poorly characterised. OBJECTIVES: To assess the prevalence of vitamin D deficiency and its association with organ dysfunction and glutamine levels in a South African (SA) ICU. METHODS: Records of 103 adult patients admitted to the Wits Donald Gordon Medical Centre ICU, Johannesburg, SA were retrospectively reviewed. 25-hydroxyvitamin D (25(OH)D) and glutamine levels were measured on admission. The association between admission vitamin D levels and glutamine levels, illness severity scores, organ support and outcomes was examined. RESULTS: On ICU admission, 66% (68/103) of patients were vitamin D deficient (<20 ng/mL) (95% confidence interval (CI) 56 - 75). Vitamin D deficiency was significantly associated with mechanical ventilation (40% v. 14%) (p=0.013) and a higher median sequential organ failure assessment (SOFA) score on admission (6 (interquartile range (IQR) 3 - 8) v. 4 (IQR 2 - 6)) (p=0.047) and on day 7 (5 (IQR 2 - 10) v. 2 (IQR 1 - 4)) (p=0.017). Median admission serum glutamine levels were 481 µmol/L, with 38% deficient (<420 µmol/L) (95% CI 28 - 48). Vitamin D deficiency status on admission was not significantly associated with median admission glutamine levels (p=0.66). CONCLUSIONS: Vitamin D deficiency is common in ICU patients in SA. Deficient patients were more severely ill and required more respiratory support. No significant relationship between deficiency and median glutamine levels was noted.

It's contrary - comorbidity does not affect survival of South Africans with colorectal cancer: An analysis from the Colorectal Cancer in South Africa cohort.

BACKGROUND: The Colorectal Cancer South Africa (CRCSA) study is an observational cohort of patients with colorectal cancer (CRC) in Johannesburg, South Africa (SA). We found that the mean age at the time of CRC diagnosis was 56.6 years, consistent with studies from SA and sub-Saharan Africa. In high-income settings, comorbidity adversely affects CRC survival, and patients are substantially older at the time of CRC diagnosis. Given the younger age at CRC diagnosis in the CRCSA cohort, we hypothesised that comorbidity may be less prevalent and have little impact on CRC survival. OBJECTIVES: To determine the prevalence of comorbidity and whether comorbidity adversely affects overall survival (OS) of CRC patients. METHODS: Patients enrolled in the CRCSA study between January 2016 and July 2018 were included. The cohort comprised a convenience sample of adults with histologically confirmed CRC, treated at the University of the Witwatersrand Academic Teaching Hospital Complex. Demographic, clinical and histological variables were collected at baseline and participants were followed up for OS. The Charlson comorbidity index (CCI) scoring system was used to classify participants as 'no comorbidity' (CCI score 0) and '1 or more comorbidities' (CCI score ≥1). A descriptive analysis of the cohort was undertaken, while survival across comorbidity groups was compared by the Kaplan-Meier method and Cox proportional hazards (PH) regression models. Multivariable Cox PH regression was performed to examine the effect of comorbidity on survival (unadjusted) and then adjusted for variables. RESULTS: There were 424 participants, and the mean (standard deviation) age was 56.6 (14.1) years (range 18 - 91). Only 19.1% of participants had ≥1 comorbidities, of which diabetes mellitus was most frequent (12.3%), followed by chronic obstructive pulmonary disease (4.7%) and cardiovascular disease (3.1%). There was no significant difference in unadjusted and adjusted risk of death for the group with ≥1 comorbidities compared with those with no comorbidity. However, an incidental finding showed a significantly increased risk of death for those receiving potentially curative treatment later than 40 days after CRC diagnosis. CONCLUSIONS: In the CRCSA cohort from Johannesburg, comorbidity is uncommon, with no significant adverse effect on OS. If potentially curative treatment is initiated within 40 days of CRC diagnosis, OS could be improved. To fully understand the epidemiology of CRC in SA, population-based registries are essential, and future research should aim to identify health system failures that lead to delays in intervention beyond 40 days in patients with CRC.

The 'ins and outs' of colonoscopy at Wits Donald Gordon Medical Centre, South Africa: A practice audit of the outpatient endoscopy unit.

BACKGROUND: In South Africa, there are no national guidelines for the conduct or quality assessment of colonoscopy, the gold standard for investigation and diagnosis of bowel pathology. OBJECTIVES: To describe the clinical profile of patients and evaluate the practice of colonoscopy using procedural quality indicators at the Wits Donald Gordon Medical Centre (WDGMC) outpatient endoscopy unit (OEU). METHODS: We conducted a prospective, clinical practice audit of colonoscopies performed on adults (≥18 years of age). A total of 1 643 patients were included in the study and variables that were collected enabled the assessment of adequacy of bowel preparation, length of withdrawal time and calculation of caecal intubation rate (CIR), polyp detection rate (PDR) and adenoma detection rate (ADR). We stratified PDR and ADR by sex, age, population group, withdrawal time and bowel preparation. CIR, PDR and ADR estimates were compared between patient groups by the χ2 test; Fisher's exact test was used for 2 × 2 tables. A p-value <0.05 was used. Benchmark recommendations by the American Society for Gastrointestinal Endoscopy (ASGE)/American College of Gastroenterology (ACG) Task Force on Colorectal Cancer (CRC) were used in this audit to assess individual endoscopist performance and that of the endoscopy unit as a whole. RESULTS: The mean age of patients was 55.7 (standard deviation (SD) 14.4; range 18 - 91) years, ~60% were female, and the majority (75.5%) were white. Of the outpatients, 77.6% had adequate bowel preparation (ASGE/ACG benchmark ≥85%). The CIR was 97.0% overall, and screening colonoscopy was 96.3% (ASGE/ACG benchmark ≥90% overall and ≥95% for screening colonoscopies). The median withdrawal time for negative-result screening colonoscopies was 5.7 minutes (interquartile range (IQR) 4.2 - 9.3; range 1.1 - 20.6) (ASGE/ACG benchmark ≥ 6minutes), and PDR and ADR were 27.6% and 15.6%, respectively (ASGE/ACG benchmark ADR ≥25%). We demonstrated a 23.7% increase in PDR and 14.1% increase in ADR between scopes that had mean withdrawal times of ≥6 minutes and <6 minutes, respectively. Although the number of black Africans in the study was relatively small, our results showed that they have similar ADRs and PDRs to the white population group, contradicting popular belief. CONCLUSIONS: The WDGMC OEU performed reasonably well against the international guidelines, despite some inadequacy in bowel preparation and lower than recommended median withdrawal times on negative-result colonoscopy. Annual auditing of clinical practice and availability of these data in the public domain will become standard of care, making this audit a baseline for longitudinal observation, assessing the impact of interventions, and contributing to the development of local guidelines.

Adult liver transplant for hepatocellular carcinoma at Wits Donald Gordon Medical Centre in Johannesburg, South Africa.

BACKGROUND: For those with unresectable hepatocellular carcinoma, liver transplantation is considered the treatment of choice. Since 2006, the transplant programme at Wits Donald Gordon Medical Centre (WDGMC) has offered liver transplantation for selected patients with hepatocellular carcinoma. While the number of patients transplanted was small, we are unaware of any published data from Southern Africa describing outcomes in this group of liver transplant recipients. The aim of this study was to describe our experience as a case series. METHODS: The records of all patients with HCC who underwent deceased donor liver transplantation between April 2006 and March 2018 were reviewed retrospectively. Data were extracted from transplant clinic patient files, histopathology and pathology laboratory reports and an existing database of all liver transplant recipients at WDGMC. Patient survival was calculated from the time of transplant and survival estimates were determined by the Kaplan-Meier method. RESULTS: Thirty-one liver transplants were reviewed. The most common causes of underlying liver disease were infectious, mostly hepatitis B virus, and diseases of lifestyle including alcoholic/non-alcoholic steatohepatitis. Median age at transplant, 57 years (IQR 44-65 years), was younger than observed internationally, but consistent with reports from Africa. Male recipients predominated, in keeping with published trends. Overall, outcomes were worse than expected but for recipients who were within the University of California at San Francisco (UCSF) criteria for transplantation; survival was comparable to previously published data. CONCLUSION: Despite limitations, this is the first documented series of patients undergoing liver transplantation for HCC in South Africa and demonstrates that good results can be achieved in appropriately selected patients.

Colorectal cancer in South Africa: An assessment of disease presentation, treatment pathways and 5-year survival.

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in South Africa (SA), and the sixth most lethal. Approximately 25% of patients will have synchronous metastatic disease at the time of their primary CRC diagnosis. Although chemotherapy is used in most stages of the disease, surgical resection of the primary tumour and metastases remains the most successful treatment modality to achieve cure or prolong survival. To date, no data on CRC presentation and management have been published in SA. OBJECTIVES: To determine CRC presentation, general management patterns and overall survival in the SA private healthcare sector. METHODS: A retrospective review of a private healthcare funder's database from 1 January 2008 to 31 December 2015. International Statistical Classification of Diseases and Related Health Problems (10th revision) (ICD-10) diagnosis codes were used to identify colorectal cancer and liver and/or pulmonary metastatic disease. Procedure codes assigned to hospital admissions were used to identify type of surgical treatment. Chemotherapy was identified by the World Health Organization Anatomical Therapeutic Chemical Classification System of medicines. Treatment patterns were determined and 5-year survival rates for these were calculated. Survival was estimated using the Kaplan-Meier method, and Cox proportional hazards regression was used for between-group comparisons of survival. Data analysis was carried out using SAS version 9.4 for Windows. RESULTS: A total of 3 412 patients were included in the study, 2 267 with CRC only and 1 145 with liver (LM) or pulmonary metastases (PM). The mean age was 64.1 years (range 21 - 97), and 54.6% were male; these did not differ statistically between the study groups. Twenty percent of patients with LM or PM underwent surgical resection of their metastases. Five-year survival rates following surgical resection of all disease for CRC only, CRCLM, CRCPM and CRCLMPM were 71.7%, 57.3%, 31.5% and 26.0%, respectively. CONCLUSIONS: SA CRC patients treated in the private healthcare sector have similar disease presentation to that in published international series, with similar outcomes following various treatment pathways; however, it seems that fewer resections of metastases are undertaken compared with international trends.

The 'ins and outs' of faecal microbiota transplant for recurrent Clostridium difficile diarrhoea at Wits Donald Gordon Medical Centre, Johannesburg, South Africa.

BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening condition that is becoming increasingly common. A persistent burden of this infectious illness has been demonstrated over the past 4 years at Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, South Africa, through implementation of active surveillance of hospital-acquired infections as part of the infection prevention and control programme. Oral treatment with metronidazole or vancomycin is recommended, but there is a major problem with symptomatic recurrence after treatment. Replacement of normal flora by the administration of donor stool through colonoscopy or nasogastric/duodenal routes is becoming increasingly popular. OBJECTIVES: To identify risk factors for the development of CDAD in patients referred for faecal microbiota transplant (FMT) and evaluate the safety of administration of donor stool as an outpatient procedure, including via the nasogastric route. METHODS: A retrospective record review of patients with recurrent CDAD referred for FMT at WDGMC between 1 January 2012 and 31 December 2016 was conducted. RESULTS: Twenty-seven patients were identified, all of whom fulfilled the criteria for recurrent CDAD. One-third were aged >65 years, and the majority were female. The most common risk factors were prior exposure to antibiotics or proton-pump inhibitors and underlying inflammatory bowel disease. Three procedures were carried out as inpatients and 24 in the outpatient gastroenterology unit. At 4-week follow-up, all patients reported clinical resolution of their diarrhoea after a single treatment and there were no recurrences. The FMT procedure was associated with no morbidity (with particular reference to the risk of aspiration when administered via the nasogastric route) or mortality. CONCLUSIONS: This case series confirms that FMT is a safe and effective therapy for recurrent CDAD. In most cases it can be administered via the nasogastric route in the outpatient department. We propose that the recently published South African Gastroenterology Society guidelines be reviewed with regard to recommendations for the route of administration of FMT and hospital admission. Meticulous prescription practice by clinicians practising in hospitals and outpatient settings, with particular attention to antimicrobials and chronic medication, is urgently required to prevent this debilitating and potentially life-threatening condition.

Adult liver transplantation in Johannesburg, South Africa (2004 - 2016): Balancing good outcomes, constrained resources and limited donors.

BACKGROUND: Liver transplantation is the standard of care for the treatment of liver failure worldwide, yet millions of people living in sub-Saharan Africa remain without access to these services. South Africa (SA) has two liver transplant centres, one in Cape Town and the other in Johannesburg, where Wits Donald Gordon Medical Centre (WDGMC) started an adult liver transplant programme in 2004. OBJECTIVES:  To describe the outcomes of the adult liver transplant programme at WDGMC. METHODS:  This was a retrospective review of all adult orthotopic liver transplants performed at WDGMC from 16 August 2004 to 30 June 2016 with a minimum follow-up of 6 months. The primary outcome was recipient and graft survival and the effect of covariates on survival. Kaplan-Meier survival analysis included all adults who underwent their first transplant for end-stage liver disease (ESLD) (N=275). Proportional hazards regression analysis using hazard ratios (HRs) was conducted to determine which covariates were associated with a significantly increased risk of mortality. RESULTS:  A total of 297 deceased-donor liver transplants were performed during the study period; 19/297 (6.4%) were for acute liver failure (ALF) and the remainder were for ESLD. The median age of recipients was 51 years (interquartile range 41 - 59), and two-thirds were male. The most common cause of ESLD was primary sclerosing cholangitis. The median follow-up was 3.2 years, and recipient survival was characterised in the following intervals: 90 days = 87.6% (95% confidence interval (CI) 83.1 - 91.0), 1 year = 81.7% (95% CI 76.6 - 85.8), and 5 years = 71.0% (95% CI 64.5 - 76.5). Allograft survival was similar: 90 days = 85.8% (95% CI 81.1 - 89.4), 1 year = 81.0% (95% CI 75.8 - 85.2), and 5 years = 69.1% (95% CI 62.6 - 74.7). The most significant covariates that impacted on mortality were postoperative biliary leaks (HR 2.0 (95% CI 1.05 - 3.80)), recipient age >60 years at time of transplant (HR 2.06 (95% CI 1.06 - 3.99)), theatre time >8  hours (HR 3.13 (95% CI 1.79 - 5.48)), and hepatic artery thrombosis (HR 5.58 (95% CI 3.09 - 10.08)). The most common infectious cause of death was invasive fungal infection. CONCLUSIONS:  This study demonstrates that outcomes of the adult orthotopic liver transplant programme at WDGMC are comparable with international transplant centres. Management of biliary complications, early hepatic artery thrombosis and post-transplant infections needs to be improved. Access to liver transplantation services is still extremely limited, but can be improved by addressing the national shortage of deceased donors and establishing a national regulatory body for solid-organ transplantation in SA.