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Kotze MJ, de Villiers JNP, Bouwens CSH, Warnich L, Zaahl MG, van der Merwe S, Oberkanins C. Molecular diagnosis of hereditary hemochromatosis: application of a newly-developed reverse-hybridization assay in the South African population. A recently developed strip-assay for hemochromatosis provides a rapid method for simultaneous detection of multiple mutations, which among others includes the HFE gene mutations V53M, V59M, H63D, H63H, S65C, Q127H, E168Q, and C282Y, previously detected in the general South African population using gel-based mutation-screening methods. The objective of the study was to determine the frequency of the relatively rare mutations in samples selected for altered iron parameters or a family history of hereditary hemochromatosis (HH) as part of the validation process of the assay for routine diagnostic purposes. The study population consisted of 451 individuals previously screened for mutations C282Y and H63D by restriction enzyme analysis in order to confirm or possibly exclude a diagnosis of HH. These individuals were subjected to mutation screening using the commercially available hemochromatosis strip-assay. Previous positive results for mutations C282Y and H63D in 233 individuals confirmed the accuracy of the reverse-hybridization assay. Mutation S65C was detected in 13 Caucasians, including three compound heterozygotes. These constituted 2% (13/600) of the chromosomes without mutations C282Y or H63D. The African-specific HFE mutation V53M was detected in one out of 11 (9%) African subjects screened. Mutation E168Q was detected in a single Caucasian individual together with mutation H63D. Our data demonstrate the value of the strip-based technology in providing a rapid and reliable comprehensive test for simultaneous analysis of multiple mutations. [ABSTRACT FROM AUTHOR]

Purpose: To assess the outcome of surgically fixated femur shaft and distal femur fractures following low-velocity civilian gunshot injuries over a 4-year period., Methods: A retrospective review was conducted on all patients who sustained femur shaft and distal femur fractures from civilian low-velocity gunshot injuries that required definitive surgical fixation between January 2014 and December 2017. Patient demographics, comorbidities, injury characteristics, duration between injury and surgical fixation and presence of complications were captured., Results: A total of 122 patients (mean age, 29.1 ± 9.5 years) were included. Supracondylar femur fractures (AO 33) accounted for 49% of total injuries, followed by femoral shaft (AO 32) and intra-articular distal femur fractures (AO 33 B & C) with 40% and 11%, respectively. Intramedullary nail fixation was the choice of treatment for femur shaft fractures (49.98%) and supracondylar fractures (63%). Intra-articular injuries were predominantly treated with distal femoral locking plates (85%). Arterial and nerve injuries were the most commonly encountered associated injuries occurring in five patients (4.1%) each. Fracture-related infection was diagnosed in two patients (1.6%). No cases of non-union and compartment syndrome were recorded., Conclusion: Femur shaft and supracondylar fractures fixated with intramedullary nails are associated with low complication rates and perfect union rates. Our study suggests that intra-articular distal femur fractures fixated with locking plates and cannulated screws have a high complication rate and poorer surgical outcomes. Non-union and compartment syndrome are rare complications of gunshot femur fractures fixated with either intramedullary nails or locking plates., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Early identification of patients at high risk of severe disease requiring referral and treatment at a high-care facility is imperative in the management of COVID-19 pneumonia in a limited-resource setting, as transfer of unstable patients can be detrimental., Objectives: To examine the value of the neutrophil-to-lymphocyte ratio (NLR) calculated on admission to a healthcare facility as a predictor of the need for early referral to a high-care facility for further treatment., Methods: We designed a cohort analytical study of 198 patients with COVID-19 pneumonia admitted to the COVID-19 unit at Universitas Academic Hospital in Bloemfontein, South Africa, between 20 May and 30 September 2021., Results: Of the 198 patients enrolled in the study, 134 (67.7%) were admitted to high care and 93 (46.9%) died. The median (interquartile range (IQR)) NLR measured on admission to the hospital was 8.09 (4.90 - 14.86), and the NLR ranged from 0.26 to 136.7. The admission NLR was statistically significantly higher in the high-care group v. the general ward group (p<0.001). After converting the NLR to log scale, to bring it closer to conditional normality, logistic regression analysis identified log NLR (odds ratio (OR) 4.089; 95% confidence interval (CI) 2.464 - 6.787; p<0.001) and age (OR 1.029; 95% CI 1.004 - 1.056; p=0.024) as significant in determining who will require high care. The area under the receiver operating characteristic curve for the combined model of NLR and age was 0.829 (95% CI 0.767 - 0.891). An NLR cut-off value of 7.5 (sensitivity 0.7462, specificity 0.7968) has been calculated as the optimal cut-off value to determine who will need high care. Admission log NLR and age were significant in determining who died (OR 2.067; 95% CI 1.404 - 3.045; p<0.001, and OR 1.043; 95% CI 1.018 - 1.068; p=0.001, respectively)., Conclusion: The NLR measured on admission and age can be used to predict whether a patient with COVID-19 pneumonia will require high care.

Purpose: The aim of this study was to quantify the overall burden of orthopaedic gunshot-related injuries at our institution over a four year period. Secondary aims included identifying complications from gunshot-related injuries and the additional burden it places on healthcare services., Methods: A retrospective review was conducted on all patients with gunshot injuries presenting to our hospital's trauma unit between January 2014 and December 2017. Patient data was recorded, and demographic data, number and type of implants, blood products used, duration of hospital admission, duration of ICU admission, radiological studies performed, and prevalence of complications were analysed., Results: A total of 1449 patients with a mean age of 28.2 ± 9.7 years (range 2.0-71.0) were included in this study. The majority of these gunshot-related orthopaedic injuries were sustained to the lower extremities and were treated non-operatively. The median duration of hospital stay was 7.0 (IQR 4.0-12.0). The most common complications identified were nerve injury (8.3%), vascular injury (6.5%), fracture-related infection (3.2%), non-union (3.1%), and compartment syndrome (1.6%). The total cost of care was ZAR 53,568,537 (USD 4,320,043) with an average cost per patient of ZAR 37,031 (USD 2986)., Conclusion: This study highlighted the burden of gunshot injuries presenting to our hospital and the strain it places on its healthcare resources. The prevalence of complications was comparable to international studies on the subject. With improved understanding of this burden, more healthcare resources can be allocated to this problem and better prevention strategies can be planned.

Tuberculosis and nutrition are intrinsically linked in a complex relationship. Altered metabolism and loss of appetite associated with tuberculosis may result in undernutrition, which in turn may worsen the disease or delay recovery. We highlight an updated Cochrane review assessing the effects of oral nutritional supplements in people with active tuberculosis who are receiving antituberculosis drug therapy. The review authors conducted a comprehensive search (February 2016) for all randomised controlled trials comparing any oral nutritional supplement, given for at least 4 weeks, with no nutritional intervention, placebo or dietary advice only in people receiving antituberculosis treatment. Of the 35 trials (N=8 283 participants) included, seven assessed the provision of free food or high-energy supplements, six assessed multi-micronutrient supplementation, and 21 assessed single- or dual-micronutrient supplementation. There is currently insufficient evidence to indicate whether routinely providing free food or high-energy supplements improves antituberculosis treatment outcomes (i.e. reduced death and increased cure rates at 6 and 12 months), but it probably improves weight gain in some settings. Plasma levels of zinc, vitamin D, vitamin E and selenium probably improve with supplementation, but currently no reliable evidence demonstrates that routine supplementation with multi-, single or dual micronutrients above the recommended daily intake has clinical benefits (i.e. reduced death, increased cure rate at 6 and 12 months, improved nutritional status) in patients receiving antituberculosis treatment. In South Africa, most provinces implement a supplementation protocol based on nutritional assessment and classification of individuals rather than on disease diagnosis or treatment status.

Background & Aims: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the obesity pandemic. We analyzed the transcriptional profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and phenotypes and functional characteristics of adipocyte tissue macrophages (ATMs), in obese patients undergoing bariatric surgery., Methods: We collected anthropometric data; plasma samples; and SAT, VAT, and liver tissues from 113 obese patients undergoing bariatric surgery at academic hospitals in Europe (Antwerp and Leuven) and South Africa. Based on clinical and histologic features, patients were assigned to the following groups: obese, NAFLD, nonalcoholic steatohepatitis (NASH), or NASH with fibrosis. Microarray analyses were performed to identify genes expressed differentially among groups. We measured levels of cytokines and chemokines in plasma samples and levels of RNAs in adipose tissues by quantitative reverse-transcription polymerase chain reaction. ATMs were isolated from patients and 13 lean individuals undergoing cholecystectomy (controls), analyzed by flow cytometry, and cultured; immunophenotypes and levels of cytokines and chemokines in supernatants were determined., Results: We observed increased expression of genes that regulate inflammation in adipose tissues from patients with NAFLD and NASH; expression of these genes increased as disease progressed from NAFLD to NASH. We found 111 genes associated with inflammation that were expressed differentially between VAT and SAT. Serum levels of interleukin 8, chemokine (C-C motif) ligand 3, and tumor necrosis factor-α correlated with liver inflammation and NAFLD activity score. We developed 2 models that could be used to determine patients' liver histology based on gene expression in VAT and SAT. Flow cytometry showed increased proportions of CD11c+CD206+ and CCR2+ macrophages in VAT from patients with NASH, and supernatants of cultured macrophages had increased levels of cytokines and chemokines compared with controls., Conclusions: VAT and SAT from patients with NAFLD and NASH have an increased expression of genes that regulate inflammation, and ATM produce increased levels of inflammatory cytokines, compared with adipose tissues from controls. We identified an expression profile of 5 genes in SAT that accurately predict liver histology in these patients. Transcript profiling: accession numbers: GSE58979 and GSE59045., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Helicobacter pylori infects the stomachs of one in two humans and can cause sequelae that include ulcers and cancer. Here we sequenced the genomes of 97 H. pylori isolates from 52 members of two families living in rural conditions in South Africa. From each of 45 individuals, two H. pylori strains were isolated from the antrum and corpus parts of the stomach, and comparisons of their genomes enabled us to study within-host evolution. In 5 of these 45 hosts, the two genomes were too distantly related to be derived from each other and therefore represented evidence of multiple infections. From the remaining 40 genome pairs, we estimated that the synonymous mutation rate was 1.38 × 10(-5) per site per year, with a low effective population size within host probably reflecting population bottlenecks and immune selection. Some individuals showed very little evidence for recombination, whereas in others, recombination introduced up to 100-times more substitutions than mutation. These differences may reflect unequal opportunities for recombination depending on the presence or absence of multiple infections. Comparing the genomes carried by distinct individuals enabled us to establish probable transmission links. Transmission events were found significantly more frequently between close relatives, and between individuals living in the same house. We found, however, that a majority of individuals (27/52) were not linked by transmission to other individuals. Our results suggest that transmission does not always occur within families, and that coinfection with multiple strains is frequent and evolutionarily important despite a fast turnover of the infecting strains within-host., Competing Interests: The authors declare no conflict of interest.

Hepatitis B remains a significant yet preventable health issue in South Africa. The introduction of the hepatitis B vaccine into the country some 18 years ago has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg positivity remain unacceptably high. Those with chronic hepatitis B virus infection have an elevated risk of developing cirrhosis with end-stage liver disease and a markedly elevated risk of hepatocellular carcinoma, independent of the presence of cirrhosis. The challenge in South Africa remains prevention through the universal vaccination coverage of all children and the identification of those with chronic hepatitis B virus infection. Over the last decade our understanding of hepatitis B and its behaviour and natural history in those with chronic infection has significantly improved. This understanding is key to identifying those who warrant further evaluation and therapy. A number of global societies have updated their guidelines in recent years. This document draws on these guidelines and serves to contextualise, for South Africa, practice guidelines for the management of chronic hepatitis B.

Objectives: To determine the current prevalence of retinopathy of prematurity (ROP) in premature babies treated with non-invasive ventilation at Tygerberg Children's Hospital, Parow, Cape Town, South Africa, and to identify risk factors associated with the development of ROP., Methods: A retrospective medical records review of infants screened for ROP during a 2-year period (January 2009 - December 2010). Infants who did not receive invasive ventilation during the first week of life were included. Twenty-four previously reported risk factors for the development of ROP were identified for use in a multivariate logistic regression (MLR) analysis., Results: A total of 356 patients were included. The overall prevalence of ROP was 21.8% and that of clinically significant ROP (CSROP) 4.4%. The risk factors with a statistically significant association with the development of ROP on MLR analysis were severe apnoea (p=0.0005) and decreasing birth weight (p=0.0382)., Conclusions: There is a low prevalence of ROP in the cohort of preterm infants treated exclusively with non-invasive ventilation in the first week of life. The risk factors of importance in our population were severe apnoea and lower birth weight. Birth weight is a practical and reproducible variable that can be used to aid development of ROP screening criteria.

Setting: Public sector primary care clinics in Free State Province, South Africa., Objectives: To investigate the effects of on-site in-service clinical skills training for nurse practitioners on tuberculosis (TB) treatment outcomes in the same clinics., Design: Analysis of TB programme data from clinics taking part in two consecutive randomised trials of educational outreach aimed at improving respiratory and human immunodeficiency virus/acquired immune-deficiency syndrome care based on the Practical Approach to Lung Health. We compared treatment outcomes between control and intervention clinics among all patients diagnosed with TB during either trial., Results: During the two trials, participating clinics treated 4187 and 2333 TB patients, respectively. Neither intervention was associated with better outcomes overall. However, among retreatment patients, cure or completion rates in intervention clinics were significantly higher during the second trial (OR 1.78, 95%CI 1.13-2.76). Patients in clinics that had received both interventions had higher cure or completion rates (OR 1.99, 95%CI 1.53-2.58) and lower default rates (OR 0.25, 95%CI 0.097-0.63) than patients in clinics that had received neither intervention., Conclusion: Although not primarily focused on TB treatment, the interventions appeared to improve successful treatment completion rates among TB retreatment cases. Integrated care programmes support attainment of important TB programme goals.

Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorly understood. We studied the genetic relationships of H. pylori isolated from 52 individuals of two large families living in a rural community in South Africa and from 43 individuals of 11 families living in urban settings in the United Kingdom, the United States, Korea, and Colombia. A 3,406 bp multilocus sequence haplotype was determined for a total of 142 H. pylori isolates. Isolates were assigned to biogeographic populations, and recent transmission was measured as the occurrence of non-unique isolates, i.e., isolates whose sequences were identical to those of other isolates. Members of urban families were almost always infected with isolates from the biogeographic population that is common in their location. Non-unique isolates were frequent in urban families, consistent with familial transmission between parents and children or between siblings. In contrast, the diversity of H. pylori in the South African families was much more extensive, and four distinct biogeographic populations circulated in this area. Non-unique isolates were less frequent in South African families, and there was no significant correlation between kinship and similarity of H. pylori sequences. However, individuals who lived in the same household did have an increased probability of carrying the same non-unique isolates of H. pylori, independent of kinship. We conclude that patterns of spread of H. pylori under conditions of high prevalence, such as the rural South African families, differ from those in developed countries. Horizontal transmission occurs frequently between persons who do not belong to a core family, blurring the pattern of familial transmission that is typical of developed countries. Predominantly familial transmission in urban societies is likely a result of modern living conditions with good sanitation and where physical contact between persons outside the core family is limited and regulated by societal rules. The patterns observed in rural South African families may be representative of large parts of the developing world.

A recently developed strip-assay for hemochromatosis provides a rapid method for simultaneous detection of multiple mutations, which among others includes the HFE gene mutations V53M, V59M, H63D, H63H, S65C, Q127H, E168Q, and C282Y, previously detected in the general South African population using gel-based mutation-screening methods. The objective of the study was to determine the frequency of the relatively rare mutations in samples selected for altered iron parameters or a family history of hereditary hemochromatosis (HH) as part of the validation process of the assay for routine diagnostic purposes. The study population consisted of 451 individuals previously screened for mutations C282Y and H63D by restriction enzyme analysis in order to confirm or possibly exclude a diagnosis of HH. These individuals were subjected to mutation screening using the commercially available hemochromatosis strip-assay. Previous positive results for mutations C282Y and H63D in 233 individuals confirmed the accuracy of the reverse-hybridization assay. Mutation S65C was detected in 13 Caucasians, including three compound heterozygotes. These constituted 2% (13/600) of the chromosomes without mutations C282Y or H63D. The African-specific HFE mutation V53M was detected in one out of 11 (9%) African subjects screened. Mutation E168Q was detected in a single Caucasian individual together with mutation H63D. Our data demonstrate the value of the strip-based technology in providing a rapid and reliable comprehensive test for simultaneous analysis of multiple mutations.

The traditional Zulu remedy impila (Callilepis laureola) can cause acute fatal hepatocellular necrosis, especially in children. We investigated the mechanism(s) of toxicity using HuH-7 hepatocytes. Impila tubers were extracted with boiling water and the aqueous extract was used at different concentrations to study the effects on the morphology of the cells. Flow cytometry and labelling with fluorescent antibodies to tubulin were also used. At high concentrations, necrosis occurred; however, at lower concentrations, the extracts gave rise to a variety of changes including hypercondensation of chromatin, multinucleate cells, nuclear fragmentation and apoptosis. In addition, we observed destruction of cytoplasmic tubulin. These findings give further insight into the mechanism of toxicity of herbal remedies containing atractyloside.

A number of traditional remedies used in South Africa contain pyrrolizidine alkaloids, some of which are hepatotoxic. We investigated the effect on human HuH-7 cells of Senecio latifolius DC., a plant that is a component of some traditional remedies and which is known to contain toxic pyrrolizidine alkaloids. Cells were also treated with extracts of a standard pyrrolizidine, retrorsine. The changes in the gross morphology of the cells were studied using light microscopy after haematoxylin and eosin staining. The cytoskeleton was investigated using fluorescence-labelled anti-beta-tubulin antibody and the nuclear organisation was studied using fluorescence-labelled antinuclear antibodies. The plant extracts gave rise to dose-dependent gross morphological changes. At high doses, we observed necrosis and at lower doses, destruction of the cytoskeleton, nuclear fragmentation and apoptosis. Doses of less than the equivalent of 330 ng/ml retrorsine led to multinucleated cells with failure in spindle formation and clumping of nuclear chromatin. This latter finding suggests that chronic low-dose treatment with such traditional remedies could give rise to teratogenic and/or carcinogenic effects.

200 dental plaster casts of Western Cape Caucasoid subjects, all of whom were under the age of 21 years, were used in this study. Mesio-distal measurements (MD lengths) were obtained of all the teeth, disregarding the third molars. This data was used to develop regression equations, for maxillary and for mandibular arches, to enable the prediction of the mesio-distal lengths of the canine and two premolars. The study identified the sum of the MD lengths of the permanent lower incisors as the best predictor. It appears that separate predictions for male and female are not warranted. The equations and the predicted values were compared with those of Moyers (1973 and 1988) and some significant differences were found. The Prediction Tables will be useful in analysis of the mixed dentition phase in patients from this population group.

In the year ending 30 June 1989, 26.8% of 5,345 deaths in the Port Elizabeth area were classified as ill-defined. A study was undertaken in an attempt to identify the reasons for the high proportion of such deaths. Copies of all death notifications and death register forms of black people in the area served by the Port Elizabeth City Health Department were collected for a 6-week period. Of the 316 deaths, 154 (48.7%) were certified by medical practitioners at a hospital, 158 (50%) by the police and 4 (1.3%) by private medical practitioners. Of the police-certified deaths 116 (73.4%) were recorded as due to 'natural causes', with the remainder being submitted to autopsy. Of the hospital deaths, 26% were not adequately described in the section for the cause of death on the death certificate. Review of national mortality data for 1985 showed that only 29.9% of ill-defined deaths (in all population groups) were certified by a medical practitioner. The prime source of deaths classified as ill-defined, both in Port Elizabeth and nationally, were those not certified by a medical practitioner. Strategies aimed at minimising the number of deaths certified by the police need to be developed.

Fifty sera collected from 12 different species of free-living game animals in game parks in the Northern Natal were tested against 8 Leptospira interrogans antigens using the microscopic agglutination test (MAT). Six out of 50 animals had titres, all less than 100. Three of these animals had titres to serovar mini, 1 animal to tarrasovi, and 3 animals had multi-serovar reactions, 1 to mini and hardjo, and 1 to tarrasovi, copenhageni and pomona.