Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

BACKGROUND: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. METHOD: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. CONCLUSION: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Factors influencing in-hospital mortality for salvage percutaneous transjugular intrahepatic portosystemic shunting in cirrhotic patients with recalcitrant variceal bleeding after failed endoscopic intervention.

BACKGROUND: Endoscopic therapy is the first-line treatment of choice for control of acute variceal bleeding (AVB). In high-risk patients with persistent AVB despite pharmacological treatment and endoscopic intervention, percutaneous transjugular intrahepatic portosystemic shunting (TIPS) provides a minimally invasive salvage method to reduce portal pressure and control bleeding. OBJECTIVES: To evaluate factors influencing in-hospital mortality after salvage TIPS (sTIPS) in patients with exsanguinating variceal bleeding despite medical treatment and endoscopic intervention. METHODS: Clinical and laboratory data were analysed in all patients treated with sTIPS following failed endoscopic therapy for AVB between August 1991 and November 2020. Factors associated with and predictors of death were determined using bivariate analysis and univariate logistic regression analysis. RESULTS: Thirty-four patients (29 men, 5 women), mean age 52 years (range 31 - 80), received sTIPS for uncontrolled (n=11) or refractory (n=23) AVB. The causes of portal hypertension were alcohol-related (n=24) and non-alcohol-related cirrhosis. Salvage TIPS controlled bleeding in 32 patients, with recurrence in 1. Ten patients died in hospital (mean 4.8 days, range 1 - 10) of liver failure (n=4), multiorgan failure (n=3), alcoholic cardiomyopathy (n=2) and uncontrolled gastric variceal bleeding (n=1). On bivariate analysis, factors associated with death were Child-Pugh (C-P) score ≥10 (p=0.006), sodium Model for End-stage Liver Disease (MELD-Na) score ≥22 (p<0.001), ≥8 units of blood transfused (p<0.001), Sengstaken-Blakemore balloon tube placement (p<0.001), endotracheal intubation (p<0.001), inotropic support (p<0.001) and endoscopically uncontrolled bleeding (p<0.001). Univariate logistic regression analysis showed that the most significant predictors of mortality were inotrope dependency (odds ratio (OR) 134; p<0.001), endotracheal intubation (OR 99; p<0.001), endoscopically uncontrolled bleeding (OR 28; p=0.001), grade 3 ascites (OR 20.9; p=0.012) and C-P grade C (OR 8.8; p=0.011). CONCLUSION: Salvage TIPS controlled variceal bleeding in 94% of patients after failed endoscopic therapy with 29% in-hospital mortality. The most significant predictors of mortality were C-P grade C, grade 3 ascites, inotrope requirement, endotracheal intubation and endoscopically uncontrolled bleeding.

A natural history of efavirenz drug-induced liver injury.

BACKGROUND: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, has been a component of first-line antiretroviral therapy (ART) in the South African HIV/AIDS programme since 2004. It is extensively used in ART programmes in other low- and middle-income countries. The natural history of the previously recognised EFV drug-induced liver injury (DILI) is not known. OBJECTIVES: To define and establish a causality assessment for EFV DILI and document its natural history by detailing a patient cohort. All relevant features characterising the patterns of clinical and histological injury, the duration of clinical and biochemical recovery and the associated mortality rate were documented. Factors associated with specific histological patterns of liver injury were analysed. METHODS: Patients were prospectively included after meeting causality and inclusion criteria for EFV DILI. Clinical, demographic and liver histological features (where possible) were documented from the time of presentation and throughout follow-up. Prednisone at 0.25 - 0.5 mg/kg was initiated at the discretion of the treating hepatologist. RESULTS: Fifty patients were prospectively included in the analysis. The median age was 34 (interquartile range (IQR) 29 - 39) years, males being older than females (p=0.014). Most (92%) were female, and 86% were of black African ethnicity. The median duration of ART at presentation was 6 months, with half of the women having initiated ART during pregnancy, at a median gestation of 24 (IQR 11 - 36) weeks. The median CD4 nadir at ART treatment initiation was 517 cells/µL, with no significant difference in CD4 nadir between those who were pregnant and those who were not (p=0.6). The median RUCAM (Roussel Uclaf Causality Assessment Method) score was 7, and among the 75% of patients who had liver biopsies, three histological patterns were identified: submassive necrosis (60%), nonspecific hepatitis (35%), and mixed cholestatic hepatitis (5%). On multivariate analysis, predictors for the development of submassive necrosis included younger age (<30 years; p=0.045), ART initiation in pregnancy (p=0.02), and a baseline CD4 count >350 cells/µL (p=0.018). For the nonspecific hepatitis group, pregnancy was also an associated factor (p=0.04). The mortality rate was 14%, with a median time from admission to death of 15 days. The median (IQR) time to initial hospital discharge was a lengthy 33 (24 - 52) days. Biochemical recovery was prolonged, necessitating a follow-up period of more than a year at an outpatient specialist clinic, with 86% of patients initiating a protease inhibitor-based ART regimen successfully. CONCLUSIONS: EFV DILI is a severe drug complication of ART with appreciable mortality and significant inpatient morbidity, requiring prolonged hospitalisation and follow-up.

Epidemiology of inflammatory bowel disease in sub-Saharan Africa: A review of the current status.

While inflammatory bowel disease (IBD) has been well characterised in the West and other parts of the world, there are little data from sub-Saharan Africa (SSA). To throw light on the current status of IBD in SSA, we performed a systematic review of the literature, extracting relevant publications. We found only 210 documented IBD cases in SSA (excluding South Africa (SA)), which were reported in 34 publications until August 2019. The majority were cases of ulcerative colitis. Only three reports, all from SA, attempted to determine IBD incidence rates. The rest were mostly case reports or small case series; the largest from Nigeria comprised 32 patients. The paucity of documented cases possibly reflects under-diagnosis and under-reporting. Major deficiencies in diagnostic and clinical capacity were noted, which need to be addressed going forward.

Prevalence and characteristics of incidental colorectal polyps in patients undergoing colonoscopy at a South African tertiary institution.

BACKGROUND: There is a lack of data on the frequency and pattern of colorectal adenomas in sub-Saharan Africa to guide diagnostic and preventive strategies for colorectal cancer (CRC) in the region. OBJECTIVES: To describe polyp characteristics and adenoma frequency in patients at average risk of CRC, who are undergoing colonoscopy for bowel symptoms at a tertiary hospital in South Africa (SA). METHODS: Colonoscopy records from the prospective endoscopy database at Groote Schuur Hospital, Cape Town, SA, from August 2014 to February 2017, were retrieved. The presence of polyps, and their morphology, size, site and number in relation to ethnicity, symptoms and colonoscopy quality indicators were analysed. The histological type and grade were obtained from laboratory records and analysed. The primary endpoint was the adenoma detection rate (ADR). Age, gender, ethnicity, symptoms, bowel preparation and caecal intubation rates were also compared between patients with adenomas and those without. RESULTS: Of 1 334 colonoscopies, 342 were performed in patients at increased risk of premalignant lesions; these were excluded from the analysis. Polyps were identified in 172 of the remaining 992 patients (17.3%), whose self-declared ethnicity was mixed race (76%), white (12%), black African (11%) or Asian (1%). The quality of bowel preparation and caecal intubation rate were similar between patients with polyps and those without. Patients with polyps were older than those without polyps (mean age 61.5 (standard deviation 12.9) v. 56.3 (17.4) years; p<0.002). On histological examination of these polyps, 119 were adenomas, 26 were hyperplastic and 27 were normal. The majority of the adenomas were tubular (80%), and there were only 6% with high-grade dysplasia. Half (51%) of the adenomas were in the proximal colon, and the overall ADR was 12%. The ADR (prevalence) was highest in white and Asian South Africans (18% each), followed by that in persons of mixed race (13%), but much lower in black Africans (5%). CONCLUSIONS: This study provides a benchmark ADR for our catchment population and potentially across Africa. There is evidence of a continuing differential colorectal neoplasia risk according to ethnicity, with fewer adenomas being detected in black South Africans.

Training South African clinician-scientists: Lessons from the University of Cape Town's intercalated programme.

In 2011, the Faculty of Health Sciences at the University of Cape Town, South Africa (SA), established the Clinician-Scientist Training Programme (UCTCSTP), consisting of intercalated BMedSci Hons/MB ChB and integrated MB ChB/MSc/PhD tracks. We report and reflect on the programme's performance and challenges. The UCTCSTP has so far enrolled 71 students: 51 have received BMedSci Hons degrees and 4 have received Master's degrees, while there are 14 BMedSci Hons, 4 MSc and 4 PhD candidates. Graduates have produced significant research outputs, and many remain actively engaged in research. The UCTCSTP has been successful in encouraging a cohort of future clinician-scientists, but should aim to broaden and improve its appeal to address the need to transform and grow the SA clinical academic workforce. As graduates progress with their postgraduate clinical training, they require institutional support and guidance, which may necessitate policy reform.

The consequences of major visceral vascular injuries on outcome in patients with pancreatic injuries: a case-matched analysis.

BACKGROUND: Major pancreatic injuries are complex to treat, especially when combined with vascular and other critical organ injuries. This case-matched analysis assessed the influence of associated visceral vascular injuries on outcome in pancreatic injuries. METHOD: A registered prospective database of 461 consecutive patients with pancreatic injuries was used to identify 68 patients with a Pancreatic Injury combined with a major visceral Vascular Injury (PIVI group) and were matched one-to-one by an independent blinded reviewer using a validated individual matching method to 68 similar Pancreatic Injury patients without a vascular injury (PI group). The two groups were compared using univariate and multivariate logistic regression analysis and outcome including complication rates, length of hospital stay and 90-day mortality rate was measured. RESULTS: The two groups were well matched according to surgical intervention. Mortality in the PIVI group was 41% (n = 28) compared to 13% (n = 9) in the PI alone group (p = 0.000, OR 4.5, CI 1.00-10.5). On univariate analysis the PIVI group was significantly more likely to (i) be shocked on admission, (ii) have a RTS < 7.8, (iii) require damage control laparotomy, (iv) require a blood transfusion, both in frequency and volume, (v) develop a major postoperative complication and (vi) die. On multivariate analysis, the need for damage control laparotomy was a significant variable (p = 0.015, OR 7.95, CI 1.50-42.0) for mortality. Mortality of AAST grade 1 and 2 pancreatic injuries combined with a vascular injury was 18.5% (5/27) compared to an increased mortality of 56.1% (23/41) of AAST grade 3, 4 and 5 pancreatic injuries with vascular injuries (p = 0.0026). CONCLUSION: This study confirms that pancreatic injuries associated with major visceral vascular injuries have a significantly higher complication and mortality rate than pancreatic injuries without vascular injuries and that the addition of a vascular injury with an increasing AAST grade of pancreatic injury exponentially compounds the mortality rate.

Molecular and cellular oncogenic mechanisms in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), as the fifth most diagnosed cancer in the world and the third leading cause of death, is a global health concern. Research stimulated by the dismal prognosis of HCC has led to significant advances in the understanding of its aetio-pathogenesis. Dysregulation of genetic, epigenetic and signalling pathways as well as tumour immunological escape mechanisms are implicated in the development of HCC. This review summarises the current knowledge of these mechanisms and argues that it is only through further understanding of their role in hepatocarcinogenesis, that new effective therapies can be developed.

Management of pancreatic injuries during damage control surgery: an observational outcomes analysis of 79 patients treated at an academic Level 1 trauma centre.

BACKGROUND: This study evaluated factors influencing mortality in a large cohort of patients who sustained pancreatic injuries and underwent DCS. METHODS: A prospective database of consecutive patients with pancreatic injuries treated at a Level 1 academic trauma centre was reviewed to identify those who underwent DCS between 1995 and 2014. RESULTS: Seventy-nine (71 men, median age: 26 years, range 16-73 years, gunshot wounds = 62, blunt = 14, stab = 3) patients with pancreatic injuries (35 proximal, 44 distal) had DCS. Fifty-nine (74.7 %) patients had AAST grade 3, 4 or 5 pancreatic injuries. The 79 patients had a total of 327 associated injuries (mean: 3 per patient, range 0-6) and underwent a total of 187 (range 1-7) operations. Vascular injuries (60/327, 18.3 %) occurred in 41 patients. Twenty-seven (34.2 %) patients died without having a second operation. The remaining 52 patients had two or more laparotomies (range 2-7). Overall 28 (35 %) patients underwent a pancreatic resection either during DCS (n = 18) or subsequently as a secondary procedure (n = 10) including a Whipple (n = 6) when stable. Overall 43 (54.4 %) patients died. Mortality was related to associated vascular injuries overall (p < 0.01), major visceral venous injuries (p < 0.01) and combined vascular and total number of associated organs injured (p < 0.04). CONCLUSIONS: Despite the magnitude of their combined injuries and the degree of physiological insult, DCS salvaged 45 % of critically injured patients who later underwent definitive pancreatic surgery. Mortality correlated with associated vascular injuries overall, major visceral venous injuries and the combination of vascular plus the total number of associated organs injured.

Prognostic factors, morbidity and mortality in pancreatic trauma: a critical appraisal of 432 consecutive patients treated at a Level 1 Trauma Centre.

BACKGROUND: This large retrospective observational cohort study evaluated prognostic factors, 30-day morbidity and mortality and complications related to the pancreas in patients who had sustained pancreatic injuries. METHODS: The records of 432 consecutive patients treated for pancreatic injuries at an urban Level 1 Trauma Centre in Cape Town between January 1982 and December 2012 were reviewed. Primary endpoints were postoperative morbidity and death. Bivariate and multivariate logistic regression analyses were used to assess significant predictors of morbidity and mortality. RESULTS: Overall mortality in 432 patients [394 men, median age 26, median RTS 7.8] was 15.7% and morbidity 66%. Bivariate logistic regression analysis showed that nine factors, age, RTS, presence of shock, need for a transfusion, volume of blood transfused, damage control surgery, AAST grade of pancreatic injury, an associated vascular injury and a repeat laparotomy were significant predictors of morbidity. In the final multivariate logistic regression analysis model however only two variables, AAST grade of pancreatic injury and a repeat laparotomy were significant predictors of morbidity. When factors associated with mortality were considered, logistic regression analysis found that 11 variables, age, RTS, the presence of shock, patients who required a major blood transfusion, the median number of units transfused, the need for a damage control laparotomy, AAST grade 3, 4, 5 pancreatic injuries, associated vascular injuries, the number of associated injuries, postoperative complications and days in ICU were significant. However in the final stepwise multivariate logistic regression analysis model only five variables, age, shock, median number of units transfused and the presence of associated complications were significant factors associated with mortality. CONCLUSIONS: Morbidity was 64% and AAST grade of pancreatic injury and a repeat laparotomy were significant predictors of morbidity. Overall mortality was 15.7%. Most deaths were due to associated injuries and were unrelated to the pancreatic injury. Five variables, age, shock, median number of units transfused and the presence of associated complications were significant factors associated with mortality. These data indicate that the magnitude of blood loss and haemorrhagic shock are primary determinants for survival and that urgent reversal of shock and control of bleeding are essential to reduce mortality in this cohort of patients.

Changing Trends and the Impact of Alcohol on the HIV/AIDS Epidemic in South Africa: Review

The association between increased HIV infection and alcohol use has been extensively studied and is established. South Africa is among one of the sub-Saharan African countries with the highest prevalence and number of people living with HIV/AIDS in the world. Although recent evidence suggests that the epidemic has stabilised; infection rates remain unacceptably high. Alcohol use is on the increase; particularly in the groups most susceptible to HIV infection; namely women and young adults; and informs poor choices with respect to safer sexual practices. This paper reviews the association between alcohol and HIV. More specifically; however; it aims to explore the potential socio-politico-biological and cultural explanations as to the factors that intersect to drive these two epidemic diseases: alcoholism and HIV/AIDS in South Africa. Understanding some of the underlying factors will provide a framework to implement public health measures to curb HIV