Outcomes of penetrating carotid artery injuries: A South African multicentre study.

BACKGROUND: This multicenter study examines the contemporary management of penetrating carotid artery injury (PCAI) to identify trends in management, outcomes, and to determine prognostic factors for stroke and death. METHODS: Data from three large urban trauma centers in South Africa were retrospectively reviewed for patients who presented with PCAI from 2012 to 2020. RESULTS: Of 149 identified patients, 137 actively managed patients were included. Twenty-four patients (17.9%) presented in coma and 12 (9.0%) with localizing signs (LS). CT angiography was performed on admission for 120 (87.6%) patients. Thirty patients (21.9%) underwent nonoperative management, 87 (63.5%) open surgery, and 20 (14.6%) endovascular stenting. Eighteen patients (13.1%) died, and 15 (12.6%) surviving patients had strokes. Ligation was significantly related to death and reperfusion to survival. A mechanism of gunshot wound, occlusive injuries, a threatened airway, a systolic blood pressure <90 mmHg, hard signs of vascular injury, a low GCS, coma, a CT brain demonstrating infarct, a high injury severity score and shock index, a low pH or HCO3, and an elevated lactate were significant independent prognostic factors for death. Ligation was unsurvivable in all patients with severe neurological deficits, whereas reperfusion procedures resulted in survival in 63% (12/19) patients with coma and 78% (7/9) with LS although with high stroke rates (coma: 25.0%, LS: 85.7%). CONCLUSIONS: Outcomes in PCAI, including patients with severe neurological deficit and stroke, are better when reperfused. Reperfusion holds the best promise of survival and ligation should be reserved for technically inaccessible bleeding injuries.

Validation of VIBe bleeding scale amongst hepatopancreatobiliary surgeons: results from an IHPBA survey.

BACKGROUND: The Validated Intraoperative Bleeding (VIBe) Scale could be used to aid assessment of intraoperative bleeding and guide the use of hemostatic products. The aim of this survey was to determine if the VIBe scale would serve as a generalizable and relevant tool for hepatopancreatobiliary(HPB) surgeons and trainees. METHODS: A standardized online VIBe training module was conducted on 67 respondents from 25 countries, after which they used the VIBe scale to score videos depicting different severities of intraoperative bleeding. Interobserver agreement was assessed using Kendall's coefficient of concordance. RESULTS: Interobserver agreement was excellent amongst all respondents with a Kendall's W of 0.923. Sub-analyses showed a difference based on seniority and level of experience: Attendings/Consultants(0.947) vs Fellows/Residents(0.879); Increasing years of practice >10(0.952) vs <10 years practice(0.890). There was excellent concordance regardless of surgical volume, percentage of procedures performed minimally invasively, area of sub-specialty, and previous involvement with VIBe surveys. CONCLUSION: This international survey in the field of HPB surgery across surgeons of various levels of experience showed that the VIBe scale could serve as an excellent tool to assess the severity of bleeding. This scale would also be useful in guiding the use and choice of hemostatic adjuncts to achieve hemostasis.

Posttraumatic Natural Killer Cell Decrease is Associated with Septic Complications.

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.

Compromised Gut Associated Lymphoid Tissue is a Risk Factor for Postoperative Septic Complications in HIV-Seropositive Trauma Patients.

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.

Procalcitonin and Bacterial Sepsis in Burn Patients in South Africa.

BACKGROUND: Burn patients are at high risk of infection, and as sepsis contributes significantly to morbidity and mortality, early diagnosis is essential. Procalcitonin (PCT) is a biomarker released in response to inflammation and specifically bacterial infection. This study aimed to determine the value of PCT as a diagnostic biomarker of sepsis in burns patients in Johannesburg, South Africa. MATERIALS AND METHODS: All adult patients admitted to two burns intensive care units in Johannesburg over a 3-year study period were included in a retrospective data review. Records of 178 patients were accessible and reviewed. RESULTS: The most significant risk factor for sepsis was percentage total body surface area burned (P = 0.012). A rise in PCT was a significant biomarker for bacterial infection in the early phase after a burn (P = 0.03) but not after day eight. PCT correlated with C-reactive protein as a biomarker for sepsis (P < 0.001), but not with other biomarkers. The mean PCT in patients who died was significantly higher on every study day until death compared with those who remained alive (P < 0.02, consistently). Patients on inotropes also had a significantly increased PCT level (P = 0.0001), as did those who were not discharged from intensive care unit by day 14. CONCLUSIONS: PCT may be useful as an adjunct biomarker of infection in burn patients and has potential as a predictive biomarker of early discharge.

Unraveling the South African Breast Cancer Story: The Relationship of Patients, Delay to Diagnosis, and Tumor Biology With Stage at Presentation in an Urban Setting.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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) aged <45 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). CONCLUSIONS: 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.

South African General Surgeon Preparedness for Humanitarian Disasters.

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% competency 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.

The Effect of Access to Information on Beliefs Surrounding Breast Cancer in South Africa.

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.

Inflammatory cytokines and angiogenic factors as potential biomarkers in South African pancreatic ductal adenocarcinoma patients: A preliminary report.

BACKGROUND/OBJECTIVES: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Indicators of breast cancer in patients undergoing microdochectomy for a pathological nipple discharge in a middle-income country.

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.

Laparoscopic versus open surgery for complicated appendicitis: a randomized controlled trial to prove safety.

BACKGROUND: To date, no randomized control trial has been performed comparing open appendectomy (OA) to laparoscopic appendectomy (LA) in complicated appendicitis. A systematic review and meta-analysis in 2010 concluded LA is advantageous to OA with less surgical site sepsis in complicated appendicitis; however, the level of evidence is weak (level 3a). The aim of the study was to determine whether LA is safe in the treatment of complicated appendicitis. Primary outcome included all-cause mortality and procedure-related mortality; secondary outcomes included intra-operative duration, rates of wound sepsis and re-intervention, length of hospital stay and re-admission rates. METHODS: One hundred and fourteen patients were randomized prospectively to either OA or LA using a computer-generated blind method. Patients who were either less than 12 years of age, had previous abdominal surgery or were pregnant were excluded. A team of senior surgeons capable of doing both OA and LA performed all procedures. RESULTS: The intra-operative duration, the rate of wound sepsis, the number of re-operations, the length of hospital stay and the rate of re-admissions between the OA and LA groups did not differ statistically. CONCLUSION: Laparoscopic appendectomy is safe in complicated appendicitis. Current Control Trials (ISRCTN92257749).

Comparison between preoperative biopsy and post-excision histology results in sarcoma: experience at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.

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.

Patterns and Outcomes in Pediatric Abdominal Tuberculosis: A Single Centre Cohort Study.

INTRODUCTION: Abdominal tuberculosis presents in a variety of ways. Different testing modalities must be applied in addition to having a high clinical suspicion to diagnose and initiate therapy. Medications have a good response; however, morbidity has been seen following surgical management of complicated presentations like intestinal obstruction and perforation. There is a paucity of studies in the pediatric age group which evaluate response to the different treatment regimen and identify factors associated with poorer outcomes in children with abdominal tuberculosis. METHODS: Patient records of 75 children with abdominal tuberculosis at a single center were evaluated using a questionnaire, covering a 14-year period from 2007 to 2021. Demographic features, presenting signs and symptoms, investigations and treatment details were studied. In- person or telephonic follow-up was conducted to identify treatment outcomes. RESULTS: Incidence of abdominal TB was 7%, of all TB children with a mean age of 10.1 years. Mesenteric lymph nodes were involved in 67% and small intestine in 33% cases. Surgery was required in 22 children. 85% children completed treatment. Small intestine involvement had higher probability of undergoing surgery. Of the 70 children with complete follow up, 64 were well and 6 children succumbed to the disease. Older age, small intestine involvement and surgery were independently associated with higher mortality. CONCLUSION: Intestinal involvement is associated with greater need for surgical intervention and greater mortality. Adolescents have poorer outcomes. Further studies are required focusing on these individual subgroups to understand the patterns of presentation, causes for mortality and prevention. LEVEL OF EVIDENCE: Level 5.

A comparative study of outcomes of burns across multiple levels of care.

BACKGROUND: Burn injuries are a significant contributor to the burden of diseases. The management of burns at specialised burn centres has been shown to improve survival. However, in low- and middle-income countries (LMICs) major burns are managed at non-specialised burn centres due to resource constraints. There is insufficient data on survival from treatment at non-specialised burn centres in LMICs. This study aimed to compare the outcomes of burns treatment between a specialised burn centre and five non-specialised centres. METHODS: A prospective cohort study was conducted on patients aged 18 years or above from January 1, 2021 to September 30, 2021. Participants were selected from the admission register at the emergency department. All burns irrespective of the mechanism of injury or %TBSA were included. Data were entered into REDCap. Statistical analysis of outcomes such as positive blood culture, length of hospital stay (LOHS) and 90-day mortality between specialised burn versus non-specialised centres was performed. Furthermore, an analysis of risk factors for mortality was performed and survival data computed. RESULTS: Of the 488 study participants, 36% were admitted to a specialised burn centre compared to 64% admitted to non-specialised centres. The demographic characteristics were similar between centres. Patients at the specialised burn centre compared to non-specialised centres had a significantly higher inhalation injury of 30.9% vs 7.7% (p < 0.001), > 10%TBSA at 83.4% vs 45.7% (p < 0.001), > 20%TBSA at 46.9% vs 16.6% (p < 0.001), and a median (IQR) ABSI score of 6 (5-7) vs 5 (4-6) (p < 0.0001). Furthermore, patients from specialised burn vs non-specialised centres had a longer median (IQR) time from injury to first burn excision at 7 (4-11) vs 5 (2-10) days, higher rate of burn sepsis 69% vs 35%, increased LOHS 17 (11-27) vs 12 (6-22) days, and 90-day mortality rates at 19.4% vs 6.4%. After adjusting for cofounding variables, survival data showed no difference between specialised burn and non-specialised centres (HR 1.8 95% CI 1.0-3.2, p = 0.05). CONCLUSION: Although it appears that the survival of burn patients managed at non-specialised centres in a middle-income country is comparable to those managed at specialised burn centres, there is uncounted bias in our survival data. Hence, a change in practice is not advocated. However, due to resource constraint specialised burn centres in addition to managing major burns should provide training and support to the non-specialised centres.

Enuresis in South African children: prevalence, associated factors and parental perception of treatment.

UNLABELLED: Study Type--Symptom Prevalence (prospective cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Nocturnal enuresis is a common childhood problem. Although its prevalence is known in many countries, no data are available from South Africa and it is difficult to extrapolate data from developed countries to a population with such diverse conditions and resource-poor settings. This study is the first to report on the 16% prevalence rate and the low level of parental knowledge of enuresis in South African children aged between 5 and 10 years. OBJECTIVES: • To establish the prevalence of NE in 5-10 year old South African children in a cross-sectional study using a parent-completed questionnaire. • To establish the parental perception and associated factors of mono-symptomatic nocturnal enuresis (MNE) treatment and treatment success rates in 5-10 year old children from South Africa. PATIENTS AND METHODS: • A total of 4700 questionnaires were distributed to children at 37 selected schools willing to participate from South Africa. Parents anonymously filled out the questionnaire. • Data were reported as frequencies and percentages of NE in tables according to different gender and age groups. • The Chi-square test compared proportions between groups and Fisher's Exact test corrected for small numbers of observations (n ≤ 5). Age differences were determined using Student's t-test. A P-value ≤ 0.5 was considered to be statistically significant. RESULTS: • The questionnaire's response rate was 72.1%, with 3389 children included in the study. • The overall prevalence of NE was 16.0%-14.4% of children suffered from mono-symptomatic NE (MNE). The prevalence of NE in boys was double that in that in girls. • Only 28.3% had received some form of treatment, whereas 13.5% had been medically treated by a doctor. Parents' awareness of treatment modalities available is outdated and most of the management of MNE was done by parents themselves, albeit with low success rates. • A positive family history was found in 50.5% of children suffering from MNE. • Constipation was a problem in 15.8% of children with enuresis. CONCLUSIONS: • This is the first study to estimate the prevalence of NE and report on the parental perception and possible associated factors of enuresis in children from South Africa. The study showed that South African children have a similar prevalence rate of NE (16%) when compared with other countries. • The possible associated factors with MNE in South Africa include constipation and a family history of enuresis. • Finally, there are low levels of parental knowledge of treatment modalities of MNE, leaving many children untreated.

Pancreatic ductal adenocarcinoma: Prognostic indicators of advanced disease.

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with high metastatic risk. Prognosis remains poor even after resection. Previously our group identified biomarkers that improved diagnostic accuracy in PDAC beyond the established diagnostic tumour marker, CA19-9. Risk factors, symptoms and circulating biomarkers associated with a PDAC diagnosis may differ from those that alter disease progression and metastasis. This study aimed at assessing the risk factors, presenting symptoms and potential prognostic biomarkers in PDAC and determine their relationship with PDAC stage and/or metastatic status. METHODS: Seventy-two PDAC patients with imaging available for TNM staging at presentation were enrolled following informed consent. Demographic and clinical data were captured. Blood was collected and 38 cytokines/angiogenic factors measured. Nonparametric association tests, univariate and multivariate logistic regression were performed using STATA version 14.2. A p-value≤0.05 was considered significant and odds ratios reported for effect size. RESULTS: Most risk factors and symptoms did not differ across the stages of cancer. Although male gender and smoking are risk factors for PDAC, the majority of study patients with metastatic PDAC were non-smoking females. In addition to CA19-9, the platelet count (p<0.01), IL-15 (p = 0.02) and GM-CSF (p<0.01) were significant, independent negative predictors of metastatic PDAC. Moreover, using specific cut-off values in a combined panel, the odds in a patient with all three biomarker levels below the cut-offs is 21 times more likely to have metastatic PDAC (p<0.0001). CONCLUSIONS: Platelet count, IL-15 and GM-CSF are potential prognostic indicators of metastatic disease in PDAC patients from our local South African population.

Shock index as a prognosticator for emergent surgical intervention and mortality in trauma patients in Johannesburg: A retrospective cohort study.

INTRODUCTION: Trauma is the leading cause of morbidity and mortality worldwide with exsanguination being the primary preventable cause through early surgical intervention. We assessed two popular trauma scoring systems, injury severity scores (ISS) and shock index (SI) to determine the optimal cut off values that may predict the need for emergent surgical intervention (ESI) and in-hospital mortality. METHODS: A retrospective analysis of patient records from a tertiary hospital's trauma unit for the year 2019 was done. Descriptive statistics, univariate and multivariate logistic regression analyses were performed. Receiver operator characteristic (ROC) curve analysis was conducted and area under the curve (AUC) reported for predicting the need for ESI in all study participants, as well as in patients with penetrating injuries alone, based on continuous variables of ISS, SI or a combination of ISS and SI. The Youdin Index was applied to determine the optimal ISS and SI cut off values. RESULTS: A total of 1964 patients' records were included, 89.0% were male and the median age (IQR) was 30 (26-37) years. Penetrating injuries accounted for 65.9% of all injuries. ISS and SI were higher in the ESI group with median (IQR) 11 (10-17) and 0.74 (0.60-0.95), respectively. The overall mortality rate was 4.5%. The optimal cut-off values for ESI and mortality by ISS (AUC) were 9 (0.74) and 12 (0.86) (p = 0.0001), with optimal values for SI (AUC) being 0.72 (0.60), and 0.91 (0.68) (p = 0.0001), respectively. CONCLUSION: ISS and SI are significant, independent prognosticators for the need of ESI and in-hospital mortality.

Trauma results in immune cell-induced intestinal epithelial damage with subsequently increased sepsis rate.

BACKGROUND: The detrimental effect of trauma on the immune system has been a subject of interest for decades. The gut-associated lymphoid tissue (GALT) of the bowel that encompasses different lymphocyte subpopulations may be an important pillar of human immunity in the context of trauma. Neither the short-term histological trauma-induced changes in the GALT nor its impact on the outcome after trauma surgery has been investigated. METHODS: This prospective, longitudinal proof-of-concept study included patients who required damage-control surgery after abdominal gunshot wounds with small bowel involvement. Bowel specimens were obtained during the index and relook operations, and the T-lymphocytic quantity therein was analyzed via immunohistochemistry. We scrutinized how the lymphocyte structure and numbers of the GALT altered, and whether the extent and nature of these changes had an impact on the postoperative outcome with regard to septic and surgical complications. RESULTS: A total of 31 damage-control patients were recruited for the study. The main histological changes between the index and relook specimen was a shift of CD8+ T cells from the lamina propria (LP) into the epithelium and a decrease of T lymphocytes in the LP. The significant increase of the intraepithelial CD8+ T cells was associated with a more extensive enterocyte apoptosis, and correlated significantly, positively with the number of postoperative septic complications. CONCLUSION: Our data support that trauma induces an immune cell-driven impairment of the intestinal epithelium, as well as an increased apoptosis of lymphocytes in the LP, which is associated with a worse clinical outcome. The underlying mechanism suggests that a therapeutic approach to minimize apoptosis in the intestine may impact the outcome of severely injured trauma patients. LEVEL OF EVIDENCE: Therapeutic/care/management, level lV.

Inflammatory cytokines and combined biomarker panels in pancreatic ductal adenocarcinoma: Enhancing diagnostic accuracy.

BACKGROUND: Early 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. METHODS: Plasma 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. RESULTS: Classification 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. CONCLUSIONS: Combined 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.

Genetic factors contributing to hypertension in African-based populations: A systematic review and meta-analysis.

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.