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Background The gut associated lymphoid tissue (GALT) is an important part of the immune system and compromised in HIV treatment-naïve as well as in HIV-seropositive patients on antiretroviral treatment (ART) due to HIV-induced changes. The influence of the impaired GALT on the postoperative complication rate after surgery for penetrating abdominal trauma has not been investigated and the hypothesis that the HIV-induced changes of the GALT contribute to septic complications postoperatively was tested. Material and methods This prospective study included patients who required a small bowel resection due to abdominal gunshot wounds. A bowel specimen was obtained in the index operation, and the T-lymphocytic quantity in the specimen was analyzed via immunohistochemistry to scrutinize whether these lymphocyte numbers had an impact on the postoperative outcome. Septic and postoperative complications were documented during the in-hospital course and the first month after discharge. Results In total, 62 patients were included in the study of which 38 patients were HIV-seronegative and 24 were HIV-seropositive. HIV-seropositive patients had a significantly lower quantity of CD4 + T cells in the GALT compared to the HIV-seronegative patients (p = 0.0001), which was also associated with a significantly higher rate of septic complications in the postoperative course. In the HIV-seropositive group, no significant differences were detected for T-lymphocytic quantity in the GALT between the HIV-treatment naïve and antiretroviral treatment groups. Conclusion The compromised GALT in HIV-seropositive patients may predispose these patients to postoperative septic complications. Antiretroviral therapy does not result in an adequate immune reconstitution in this tissue.

Background There has been paucity in prospective studies investigating trauma-induced changes in the cellular immunity of HIV-seropositive patients and their impact on the clinical outcome after trauma surgery. The role of natural killer (NK) cells especially has not yet been fully elucidated, and the function of this lymphocyte subtype in the immune defense after trauma is still under debate. Methods This prospective study included patients requiring surgery for abdominal gunshot wounds. A blood specimen was obtained on admission, 48 hours after the index operation and, in case of damage control surgery, 48 hours after the first planned second look operation. The quantity and changes of T-, B- and NK cells were analyzed via flow cytometry to investigate whether these numbers had an impact on the postoperative outcome. Results A total of 62 patients were recruited in the analysis of which 38 were HIV-negative and 24 HIV-seropositive. After surgery, HIV-negative patients had a more severe decrease of their CD4+ T cells compared to the HIV-seropositive patients. Trauma resulted in a severe decrease of NK cells irrespective of the HIV-serostatus. Patients with more extensive NK cell drop had a significantly higher postoperative complication rate. Conclusions Our data support the association of trauma-induced NK cell decrease with a subsequent significantly higher rate of septic and surgical complications and suggest that these immune cells might play an important role in antibacterial immunity. Strengthening the NK cell function or limiting their decrease in the postoperative course might be of therapeutic value in severely injured trauma patients.

Background. Breast cancer is the most common cancer in women in many low- and middle-income countries, and often presents at an advanced stage that affects prognosis irrespective of the care available. Although patient-related delay is commonly cited, the reasons for delay and the relationship of delay to stage are still poorly documented, especially in Africa.Objectives. To identify where patient-related socioeconomic delays occur and how these relate to stage at presentation.Methods. Consecutive women with a new breast cancer diagnosis were prospectively invited to complete a questionnaire on their socioeconomic characteristics and ability to access care. Clinical stage at presentation was documented.Results. Over 14 months, 252 women completed the questionnaire (response rate 71.6%). Their median age was 55 years (interquartile range 44 - 65), with 26.5% aged

Background Humanitarian medical organizations provide surgical care for a broad range of conditions including general surgical (GS), obstetric and gynecologic (OBGYN), orthopedic (ORTHO), and urologic (URO) conditions in unstable contexts. The most common humanitarian operation is cesarean section. The objective of this study was to identify the proportion of South African general surgeons who had operative experience and current competency in GS, OBGYN, ORTHO, and URO humanitarian operations in order to evaluate their potential for working in humanitarian disasters. Methods This was a cross-sectional online survey of South African general surgeons administered from November 2017–July 2018. Rotations in OBGYN, ORTHO, and URO were quantified. Experience and competency in eighteen humanitarian operations were queried. Results There were 154 SA general surgeon participants. Prior to starting general surgery (GS) residency, 129 (83%) had OBGYN, 125 (81%) ORTHO, and 84 (54%) URO experience. Experience and competency in humanitarian procedures by specialty included: 96% experience and 95% competency for GS, 71% experience and 51% com- petency for OBGYN, 77% experience and 66% competency for ORTHO, and 86% experience and 81% competency for URO. 82% reported training, and 51% competency in cesarean section. Conclusions SA general surgeons are potentially well suited for humanitarian surgery. This study has shown that most SA general surgeons received training in OBGYN, ORTHO, and URO prior to residency and many maintain competence in the corresponding humanitarian operations. Other low- to middle-income countries may also have broad-based surgery training, and the potential for their surgeons to offer humanitarian assistance should be further investigated.

Several studies have investigated the association of differentially expressed cytokines with pancreatic ductal adenocarcinoma (PDAC), but none in African countries. This study aimed at investigating T-helper (Th) cell and angiogenic markers as diagnostic or prognostic biomarkers for PDAC in Black South Africans.We conducted a prospective, case-control study comprising of 34 PDAC patients and 27 control participants with either critical limb ischemia, abdominal aortic aneurysm or other abdominal pathology from causes other than pancreatic disease. Plasma levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, IL-17A, VEGF, sVEGF-R1, FGF, PIGF, PDGF and P-selectin were measured using commercially available cytometric bead array, ELISA and multi-analyte Luminex kits.Significantly higher levels of IFN-γ (p 0.001), TNF (p 0.001), IL-2 (p = 0.001), IL-4 (p 0.01), IL-10 (p 0.01), IL-17A (p 0.01), PlGF (p 0.0001) and basic FGF (p 0.0001) were found in cases compared to control participants. PDAC patients with irresectable tumours had higher levels of VEGF (p = 0.02) and IL-6 (p = 0.01). A univariate analysis showed significant associations between IFN-γ, TNF, IL-10, -4, -2, basic FGF, PlGF and PDAC. In a multivariate logistic regression model, basic FGF (p = 0.002) and PlGF (p = 0.007) were independent risk factors for PDAC with a combined sensitivity of 71% and specificity of 100%.Our preliminary data suggests a potential role for basic FGF and PlGF as diagnostic, and VEGF and IL-6 as prognostic biomarkers of PDAC in Black South African patients.

BackgroundEarly diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenged by the absence of accurate early diagnostic and prognostic biomarkers. CA19-9 is the established, diagnostic tumour marker in PDAC, despite its limitations. Effective primary screening using circulating biomarker panels have only been considered in a handful of studies and we investigated whether combinations of inflammatory cytokines and angiogenic factors in multivariate logistic models could facilitate earlier diagnosis in our South African setting.MethodsPlasma levels of 38 cytokines and angiogenic factors were measured in 131 Black South African patients, 85 with PDAC, 25 with benign biliary pathology (BBP) and 21 benign non-HPB controls (BC), by use of human magnetic multiplex screening assays. Multivariate biomarker panels were developed by identifying the top performing biomolecules from univariate logistic regression. Receiver-operator characteristic (ROC) curves and area under the ROC curve (AUC) are reported.ResultsClassification modelling to distinguish PDAC patients from BC showed that a panel of CA19-9 and CXCL10 (IP-10) demonstrated improved diagnostic power over CA19-9 alone (AUC = 0.977 vs. AUC = 0.807, p-value = 0.001). A combined panel including age, BMI and IL-15 showed significant diagnostic power in discriminating PDAC from BBP (AUC = 0.952, p < 0.0001). Finally, a combined panel of IL-8, IL-15 and gender demonstrated diagnostic accuracy (AUC = 0.830, p < 0.0001) in distinguishing PDAC in the presence of jaundice from benign controls with either jaundice, choledocholithiasis or common bile duct injury.ConclusionsCombined biomarker panels improve diagnostic accuracy in PDAC. In addition to CA19-9, cytokines CXCL10, IL-8 and IL-15 are strong additions to diagnostic biomarker panels in PDAC in Black South Africans.

Introduction: Surgical systems are integral to successful, safe and cost effective clinical practice and must balance surgical demands on consumable items and their costs. Suture material is a key consumable resource, and was evaluated in an audit of consumable use and cost as well as the procurement systems within the South African Gauteng public health care sector.Aims: To determine suture use and cost in the four commonest general surgical procedures – abdominal wall closure, mastectomy, appendicectomy and inguinal hernia repair – in three academic Gauteng hospitals. Performance and availability were evaluated as a secondary aim in suture material use. Methods: A prospective observational study. Suture use was documented by the surgeon at the time of the procedure and qualitative investigation at relevant hospital departments determined suture material procurement and expenditure.Results: The surgeons in three facilities documented consistent material type and average number of units used; however, in some cases there was a lack of availability of appropriate material and breakage of generic material intraoperatively. There is no consistent and consolidated electronic record-keeping of suture stock and cost in all three hospitals, therefore cost of suture material used was not obtainable.Conclusion: Clinical deficiencies in availability and quality of material may have adverse implications for patient health, healthcare costs and budgets through procedure-related complications and should be investigated. There is a lack of communication between the financial management, procurement officers, hospital and theatre stores and theatre staff. It is suggested that clinical protocols and system-based strategies be put in place to manage surgical consumables.

Adverse outcomes from breast cancer disproportionately affect women in sub-Saharan Africa, with delay the most studied contribution to advanced stage at presentation. However, tumor molecular biology and its contribution to advanced stage are yet to be explored.Patients newly diagnosed with breast cancer in a South African tertiary breast center completed a questionnaire and file review concerning socioeconomics, delay to care, stage at presentation, and molecular characteristics. Logistic regression was done to determine the relative risk of advanced stage presentation.Advanced stage was present in 70.1% (n = 162) of the 231 participants, with 55.8% stage III (n = 129) and 32% (n = 72) having a T4 tumor. The median age was 56 y with 21.6% (n = 47) aged45 y. Most common subtype was luminal B (57.7%, n = 128) followed by luminal A (21.6%, n = 48), triple negative (13.9%, n = 31), and HER2 positive (6.7%, n = 15). Lobular cancer (incidence risk ratio [IRR], 1.29; 95% confidence interval [CI], 1.03-1.62), high grade and intermediate grade tumors (IRR, 1.90; 95% CI, 1.15-3.13 and IRR, 1.95; 95% CI, 1.18-3.22, respectively), high Ki67 proliferation index (IRR, 1.30; 95% CI, 1.02-1.66), and HER2 overexpression (IRR, 1.32; 95% CI, 1.12-1.55) were more likely to present with advanced disease, as were luminal B (HER2+) cancers (adjusted IRR [aIRR], 1.46; 95% CI, 1.10-1.95). Although on univariate analysis Black and young participants were both more likely to have advanced stage (IRR, 1.23; 95% CI, 1.01-1.49 and IRR, 1.25; 95% CI, 1.04-1.51, respectively), in multivariate analysis controlling for tumor biology and delay, these were no longer significant (aIRR, 1.12; 95% CI, 0.91-1.37 and aIRR, 1.17; 95% CI, 0.94-1.48, respectively).Tumor biology has a compelling role in the etiology of advanced-stage disease irrespective of socioeconomic factors. Accurate pathologic assessment is important in planning breast cancer care in Africa.

In a systematic review, the authors explored genetic association studies of essential hypertension in African populations. Studies reporting on the association of polymorphism(s) with hypertension in African populations were included. Appropriate studies were pooled using random effects model meta-analysis, under six potential inheritance models. In all, 46 polymorphisms in 33 genes were investigated for their association with hypertension or blood pressure levels. Meta-analysis was possible for three single nucleotide polymorphisms: rs4340, rs699, and rs5186. An association was found between rs5186, rs699, and hypertension under allele contrast and homozygous codominant models (odds ratio, 1.63 [95% confidence interval, 1.04–2.54] and 4.01 [95% confidence interval, 1.17–13.80] for rs5186, respectively; and 1.80 [95% confidence interval, 1.13–2.87] for rs699). Findings were mostly robust in sensitivity analyses. According to the systematic review, there is currently insufficient evidence on the specific polymorphisms that pose the risk of hypertension in African populations. Large-scale genetic studies are warranted to better understand susceptibility polymorphisms that may be specific to African populations.

Breast cancer is the most common cancer affecting women in South Africa. There is little knowledge of beliefs to help identify key areas to improve support and education in this demographically and culturally diverse population. Women with a variety of demographic and socioeconomic characteristics accessing care for breast cancer were asked their agreement to statements of knowledge and beliefs about breast cancer. Of the 259 participants, positive statements of medical cure (87.9%) and family support (90.5%) were most commonly believed. Beliefs in faith-based cure and alternative treatments were also present (79.5 and 24.9%, respectively). Negative beliefs were initially more likely in black patients (RR: 11.57, 95%CI: 1.37-97.69) as was belief of cancer as a punishment (RR: 6.85, 95%CI: 1.41-33.21). However, in multivariate analysis adjusting for age, education and access to information (by newspaper, Internet and confidence in reading and writing), there was no difference between racial groups or hospital attended. Reading a newspaper or accessing the Internet was the most protective against belief that cancer was a punishment or curse (Internet use: aRR: 0.12, 95%CI: 0.02-0.99), belief in alternative methods of cure (newspaper use: aRR: 0.51, 95%CI: 0.27-0.96) and the negative beliefs of death and disfigurement (Internet use: aRR: 0.00, 95%CI: 0.00-0.00). Positive expressions of cure and beating cancer were found equally in all women. Attitudes and beliefs about cancer showed little independent demographic or socioeconomic variance. Negative beliefs were mitigated by access to information and confidence in literacy.

Background The management of a pathological nipple discharge often involves surgery for the exclusion of a malignant etiology. This study aimed to determine the prevalence of cancer in patients who had microdochectomy for pathological nipple discharge in a population in South Africa and to evaluate patients' demographics and clinical characteristics as indicators of underlying cancer and make recommendations for their management in resource-limited settings. Materials and methods Clinical, radiological, and histological data from 153 patients who underwent a microdochectomy for a pathological nipple discharge at two South African breast clinics was collected. Results Invasive or in situ cancer was found in 12 patients (7.84%), and in all patients, cancer was associated with a bloody nipple discharge. Bloody discharge had a sensitivity of 100% in indicating cancer, specificity of 55.32%, positive predictive value of 16%, and negative predictive value of 100%. Patients with breast cancer were also more likely to be aged 55 y or older ( P = 0.04). Preoperative mammogram and ultrasound were poor in detecting cancer (0/12). Conclusions In our population, a bloody discharge in women aged 55 years or older should mandate a microdochectomy, with selective surgery for younger women and those with nonbloody discharges. Thorough clinical examination to determine the true color and nature of the discharge is vital in the initial assessment of these patients. Preoperative radiology is not helpful in determining the presence of cancer (in an isolated pathological nipple discharge), and microdochectomy still remains the gold standard in diagnosing cancer in these patients.

Objectives A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. Materials and Methods A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Results Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19–9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Conclusion Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals.

Central aortic blood pressure (BP; BPc) predicts outcomes beyond brachial BP. In this regard, the application of a generalized transfer function (GTF) to radial pulse waves for the derivation of BPc is an easy and reproducible measurement technique. However, the use of the GTF may not be appropriate in all circumstances. Although the peak of the second shoulder of the radial waveform (P2) is closely associated with BPc, and, hence, BPc may be assessed without the need for a GTF, whether P2-derived BPc is associated with adverse cardiovascular changes independent of brachial BP is uncertain. Thus, P2- and GTF-derived aortic BPs were assessed using applanation tonometry and SphygmoCor software. Left ventricular mass was indexed for height 1.7 (n=678) and carotid intima-media thickness (IMT; n=462) was determined using echocardiography and vascular ultrasound. With adjustments for nurse-derived brachial pulse pressure (PP), P2-derived central PP was independently associated with left ventricular mass indexed for height 1.7 (partial r =0.18; P r =0.40; P 1.7 : partial r =0.17, P r =0.37, P r =−0.21 to 0.05). Twenty-four–hour, day, and night PP-target organ relations did not survive adjustments for nurse-derived brachial BP. In conclusion, central PP derived from P2, which does not require a GTF, is associated with cardiovascular target organ changes independent of brachial BP. Thus, when assessing adverse cardiovascular effects of aortic BP independent of brachial BP, P2-derived measures may complement GTF-derived measures of aortic BP.

Diabetes is a significant major risk factor for peripheral arterial disease (PAD) and critical limb ischaemia (CLI), the latter which is also the most common cause of amputation in these patients. Revascularisation of the lower extremities of such patients is imperative for limb salvage and has become first-line therapy. However, the incidence of restenosis following endovascular stenting is very high and is largely due to neo-intimal hyperplasia (NIH), the regulation of which is for the greater part not understood. This article therefore reviews our understanding on the regulation of NIH following stent-induced vascular injury, and highlights the importance of future studies to investigate whether the profile of vascular progenitor cell differentiation, neo-intimal growth factors and lumen diameters predict the severity of post-stent NIH in the peripheral arteries. Results from future studies will (1) better our understanding of the regulation of NIH in general, (2) determine whether combinations of any of the vascular factors discussed are predictive of the extent of NIH postoperatively, and (3) potentially facilitate future therapeutic targets and/or change preventive strategies.

Background. Tumour size, grade and subtype are the main prognostic factors in adult patients presenting with soft-tissue sarcoma. Planning for appropriate management, including the need for additional staging investigations and neoadjuvant therapy, is dependent on reliable preoperative histopathological results. Objectives. To determine whether there is agreement between preoperative and post-excision histological findings in patients presenting with soft-tissue sarcoma, and whether the agreement is influenced by the subtypes of sarcomas. Patients and methods. Records of adult patients who had soft-tissue sarcomas excised were reviewed. Kaposi’s sarcoma and gastrointestinal stromal tumours were excluded. Data were retrieved from the Department of Anatomical Pathology of the National Health Laboratory Service and theatre records at Chris Hani Baragwanath Academic Hospital, and included patient demography, tumour sites and size, HIV status, biopsy types and post-excision histological findings. Results. Records of 153 patients were found (median age 44 years). The majority of the sarcomas were >5 cm in diameter, deep seated and localised in extremities. The commonest subtype, irrespective of HIV status, was dermatofibrosarcoma protuberans. Fine-needle aspiration biopsy (FNAB) results were inaccurate in determining the malignant nature, grade and subtype of sarcoma. Rates of accurate tumour subtype classification following core needle and incision biopsies when compared with post-excision histological findings were 73.1% and 78.3%, respectively. Conclusion. FNAB should not be used in the primary evaluation of soft-tissue tumours. A report of spindle cells on the FNAB smear should be followed by core needle or incision biopsy. Incision biopsy is superior to core needle biopsy in the classification of sarcomas by subtype.