Accuracy of CT Scan for Detecting Hollow Viscus Injury in Penetrating Abdominal Trauma.

BACKGROUND: In penetrating abdominal trauma, computed tomography (CT) is routinely performed to evaluate stable patients for selective non-operative management (SNOM). Triple-contrast CT (oral, rectal, and IV) has traditionally been used. However, due to its disadvantages, most trauma centres, including our unit at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), now perform single-contrast intravenous-only CT scans. We performed a retrospective review to determine the accuracy of single-contrast CT scans for detecting hollow viscus injuries (HVI) in penetrating abdominal trauma. METHODS: A retrospective review of all patients who presented to CMJAH with penetrating abdominal injuries was performed between 01 August 2017 and 31 August 2019 and were evaluated for SNOM with CT (IV contrast only). Patient records were reviewed to determine pertinent demographics, mechanism, and site of injury, as well as metabolic parameters. CT findings were compared to findings at laparotomy. RESULTS: A total of 437 patients met the inclusion criteria. The majority were male (92.7%), with a mean age of 31.5 yrs (SD 8.7). Injuries were predominantly due to stab wounds (72,5%, n = 317). CT scan was negative in 342 patients, of which 314 completed SNOM successfully. A total of 93 patients proceeded to laparotomy. CT had a sensitivity of 95.1%, specificity of 44.2%, positive predictive value of 57.4%, and negative predictive value of 92%. CONCLUSION: Single-contrast CT in penetrating abdominal trauma is a valuable investigative tool in identifying patients for SNOM. Features of HVI on single-contrast CT are not very specific and should be interpreted along with other clinical factors including wound trajectory and serial abdominal examinations. Other associated injuries such as diaphragmatic and solid organ injuries should be considered in the final management plan.

Application of Drug Repurposing-Based Precision Medicine Platform for Leukaemia Patient Treatment.

Drug resistance in leukaemia is a major problem that needs to be addressed. Precision medicine provides an avenue to reduce drug resistance through a personalised treatment plan. It has helped to better stratify patients based on their molecular profile and therefore improved the sensitivity of patients to a given therapeutic regimen. However, therapeutic options are still limited for patients who have already been subjected to many lines of chemotherapy. The process of designing and developing new drugs requires significant resources, including money and time. Drug repurposing has been explored as an alternative to identify effective drug(s) that could be used to target leukaemia and lessen the burden of drug resistance. The drug repurposing process usually includes preclinical studies with drug screening and clinical trials before approval. Although most of the repurposed drugs that have been identified are generally safe for leukaemia treatment, they seem not to be good candidates for monotherapy but could have value in combination with other drugs, especially for patients who have exhausted therapeutic options. In this review, we highlight precision medicine in leukaemia and the role of drug repurposing. Specifically, we discuss the several screening methods via chemoinformatic, in vitro, and ex vivo that have facilitated and accelerated the drug repurposing process.

Prospects of Delivering Natural Compounds by Polymer-Drug Conjugates in Cancer Therapeutics.

Synthetic chemotherapeutics have played a crucial role in minimizing mostly palliative symptoms associated with cancer; however, they have also created other problems such as system toxicity due to a lack of specificity. This has led to the development of polymer-drug conjugates amongst other novel drug delivery systems. Most of the formulations designed using delivery systems consist of synthetic drugs and face issues such as drug resistance, which has already rendered drugs such as antibiotics ineffective. This is further exacerbated by toxicity due to the long-term use. Given these problems and the fact that conjugation of synthetic compounds to polymers has been relatively slow with no formulation on the market after a decade of extensive studies, the focus has shifted to using this platform with medicinal plant extracts to improve solubility, specificity and increase drug release of medicinal and herbal bioactives. In recent years, various plant extracts such as flavonoids, tannins and terpenoids have been studied extensively using this approach. The success of formulations developed using novel drug-delivery systems is highly dependent on the tumour microenvironment especially on the enhanced permeability and retention effect. As a result, the compromised lymphatic network and 'leaky' vasculature exhibited by tumour cells act as a guiding principle in the delivery of these formulations. This review focuses on the state of the polymer-drug conjugates and their exploration with natural compounds, the progress and difficulties thus far, and future directions concerning cancer treatment.

Synthesis of fluorescence labelled aptamers for use as low-cost reagents in HIV/AIDS research and diagnostics.

Aptamers are nucleic acids selected by systematic evolution of ligands by exponential enrichment. They have potential as alternatives to antibodies in medical research and diagnostics, with the advantages of being non-immunogenic and relatively inexpensive to produce. In the present study, gp120 aptamers conjugated with fluorescein isothiocyanate (FITC) were generated, which could interact with HIV-1 gp120. A previously isolated gp120 aptamer, CSIR 1.1, was conjugated with FITC by incubation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and imidazole. The conjugation and binding to the glycoprotein were confirmed by flow cytometry. FITC conjugated aptamers showed an increase in fluorescence emission 24-fold higher than baseline, and this difference was statistically significant (P=0.0016). Compared with a commercially available biotinylated anti-gp120 antibody, detected using FITC conjugated streptavidin, the emission of fluorescence obtained from the FITC-conjugated aptamer was 8-fold higher, suggesting a stronger interaction with gp120. In addition, the FITC conjugated aptamer neutralized HIV-1 pseudoviruses with an average IC50 of 21.3 nM, similar to the parent aptamer that had an IC50 of 19.2 nM. However, the difference in inhibition between the two aptamers was not statistically significant (P=0.784). These results indicate that the FITC-conjugated aptamer generated in the present study could potentially be used as a low-cost reagent in HIV/AIDS research and diagnostics.

Chemokine receptor 8 expression may be linked to disease severity and elevated interleukin 6 secretion in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease, which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal. The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely, mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP). Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial. AIM: To identify the role of the chemokine receptor 8 (CCR8), expressed by T-helper type-2 Lymphocytes and peritoneal macrophages, and its possible association to Interleukin (IL)-6 and AP stratification. METHODS: This study was a prospective case-control study. A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital. Bioassays were performed on 29 patients (14 MAP, 11 MSAP, and 4 SAP) and 6 healthy controls as part of a preliminary study. A total of 12 mL of blood samples were collected at Day (D) 1, 3, 5, and 7 post epigastric pain. Using multiplex immunoassay panels, real-time polymerase chain reaction (qRT-PCR) arrays, and multicolour flow cytometry analysis, immune response-related proteins, genes, and cells were profiled respectively. GraphPad Prism™ software and fold change (FC) analysis was used to determine differences between the groups. P<0.05 was considered significant. RESULTS: The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P = 0.001 and P = 0.013 respectively, in a multiplex assay. When a FC of 2 was applied to identify differentially expressed genes using RT2 Profiler, CCR8 was shown to increase steadily with disease severity from MAP (1.33), MSAP (38.28) to SAP (1172.45) median FC. Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log10, compared to healthy control respectively at D3. The findings also showed differing lymphocyte and monocyte cell frequency between the groups. With monocyte population frequency as high as 70% in MSAP at D3. CONCLUSION: The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.

Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman's correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.