Prevalence and Characteristics of HIV-Associated Stroke in a Tertiary Hospital Setting in South Africa.

BACKGROUND AND OBJECTIVES: Antiretroviral treatment (ART) era HIV-associated stroke data from sub-Saharan Africa are limited. We determined the prevalence of HIV in patients presenting with acute symptomatic stroke and compared risk factors, clinical characteristics, and brain imaging with age-matched stroke patients without HIV. METHODS: We conducted a retrospective study of adults presenting with any type of stroke to Tygerberg Hospital in a 12-month period. Patients living with HIV (PLWH) and HIV-uninfected (HIV-) patients were matched based on age group (1:2 ratio). Patients were identified by keyword search, while HIV status was ascertained from laboratory data. Clinical and imaging data were extracted from medical records. RESULTS: Among 884 patients presenting with acute strokes, the minimum prevalence of HIV infection was 9.3% (95% CI: 7.4%-11.2%), with 496 patients (56.1%) with negative HIV status and 306 patients with unknown HIV status (34.6%). The mean age at presentation in PLWH was 46 (±11) years compared with 55 (±14) years in HIV- patients (p < 0.001). Smoking was less prevalent in PLWH with an adjusted relative risk ratio of RR = 0.58 (95% CI: 0.39-0.86). Concurrent infection was more prevalent in PLWH (25.6% vs 4.9%, p ≤ 0.001) with an adjusted relative risk ratio of RR = 2.07 (95% CI: 1.49-2.84), largely in patients with a CD4 count <200 cells/µL. PLWH with higher CD4 counts (≥200 cells/µL, 51.3%) had more traditional risk factors and less concurrent infection. Among PLWH, 68.3% were on ART, and 39.3% of them had been started or restarted on ART within the past 6 months. Basal ganglia infarcts (35.6% vs 18.3%, p = 0.014) and multiple vascular territory involvement (25.4% vs 7.7%, p = 0.002) were more common in PLWH. Clinical presentation, ischemic stroke type, and in-hospital outcomes did not differ between the groups. DISCUSSION: Stroke patients with HIV were younger, had less traditional cardiovascular risk factors, and more concurrent infections than patients without HIV, especially those with a lower CD4 count. Recent ART initiation or reinitiation rates were high. Significant differences in CT brain imaging findings were seen. Understanding the multifactorial mechanisms underlying increased stroke risk, including associated infections and potential ART-associated immune reconstitution, is crucial and needs further study.

After-hour trauma-radiograph interpretation in the emergency centre of a District Hospital.

Introduction: Plain radiographs remain a first-line trauma investigation. Most trauma radiographs worldwide are reported by junior doctors. This study assesses the accuracy of after-hour acute trauma radiograph reporting by emergency centre (EC) doctors in an African district hospital. Methods: An institutional review board approved retrospective descriptive study over two consecutive weekends in February 2020. The radiologist report on the admission radiographs of adult trauma patients was compared with the initial EC interpretation. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for EC interpretation were calculated with 95% confidence intervals (95%CI). The association between reporting accuracy and anatomical region, mechanism of injury, time of investigation, and the number of abnormalities per radiograph was assessed. Results: 140 radiographs were included, of which 49 (35%) were abnormal. EC doctors recorded (95%CI) 77% (69-84%) accuracy, 38% (25-54%) sensitivity, 97% (91-99%) specificity, 86% (65-95%) PPV and 76% (71-80%) NPV. Performance was associated with the anatomical region (p=0.02), mechanism of injury (p=<0.01) time of day (p=0.04) and the number of abnormalities on the film (p=<0.01). The highest sensitivity was achieved in reports of the appendicular skeleton (42%) and in the setting of simple blunt trauma (62%). Overall accuracy was in line with the range (44%-99%) reported in the international literature. Discussion: Accurate reporting of acute trauma radiographs is challenging. Key factors impact performance. Further training of junior doctors in this area of clinical practice is recommended. Future work should focus on assessing the impact of such training on reporting performance.

Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss.

Type I protein arginine methyltransferases (PRMTs) catalyze asymmetric dimethylation of arginines on proteins. Type I PRMTs and their substrates have been implicated in human cancers, suggesting inhibition of type I PRMTs may offer a therapeutic approach for oncology. The current report describes GSK3368715 (EPZ019997), a potent, reversible type I PRMT inhibitor with anti-tumor effects in human cancer models. Inhibition of PRMT5, the predominant type II PRMT, produces synergistic cancer cell growth inhibition when combined with GSK3368715. Interestingly, deletion of the methylthioadenosine phosphorylase gene (MTAP) results in accumulation of the metabolite 2-methylthioadenosine, an endogenous inhibitor of PRMT5, and correlates with sensitivity to GSK3368715 in cell lines. These data provide rationale to explore MTAP status as a biomarker strategy for patient selection.

The Role of the Integrated Digital Radiology System in Assessing the Impact of Patient Load on Emergency Computed Tomography (CT) Efficiency.

Time-critical management is of particular significance in the trauma and emergency setting, where intervals from patient arrival to diagnostic imaging and from imaging to radiology report are key determinants of outcome. This study, based in the Trauma and Emergency Unit of a large, tertiary-level African hospital with a fully digital radiology department, assessed the impact of increased workload on computerised tomography (CT) efficiency. Sequential, customised searches of the institutional radiology information system (RIS) were conducted to define two weekends in 2016 with the lowest and highest emergency CT workloads, respectively. The electronic RIS timestamps defining the intervals between key steps in the CT workflow were extracted and analysed for each weekend. With the exception of radiologist reporting time, workflow steps were significantly prolonged by increased workload. This study highlights the potential role of the integrated digital radiology system in enabling a detailed analysis of imaging workflow, thereby facilitating the identification and appropriate management of bottlenecks.

Poly Ethoxy Ethyl Glycinamide (PEE-G) Dendrimers: Dendrimers Specifically Designed for Pharmaceutical Applications.

Poly ethoxy ethyl glycinamide (PEE-G) dendrimers have been specifically designed and synthesized with the aim of providing a readily available dendrimer scaffold that can be used to make products that can meet the stringent requirements of pharmaceutical applications. The synthesis has been refined to produce dendrimers that are of high HPLC purity. The suitability of PEE-G dendrimers for their designed use has been verified by subsequent measurements to demonstrate that they are of high stability, high aqueous solubility, low cytotoxicity, low immunogenicity and with low in vivo toxicity in an escalating-dose rat study. PEE-G dendrimers therefore provide a useful scaffold for researchers wanting to develop dendrimer-based drug candidates.

Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?

An approach and preliminary results for utilizing legacy MEK inhibitors as templates for a reiterative structural based design and synthesis of novel, type III NCKIs (non-classical kinase inhibitors) is described. Evidence is provided that the MEK-pocket or pockets closely related to it may exist in kinases other than MEK.