Analysis of 5 years of morbidity and mortality conferences in a metropolitan South African trauma service

Background. Since 2008 the Pietermaritzburg Metropolitan Trauma Service (PMTS) has run a structured, self-reporting, metropolitan morbidity and mortality conference (MMC). In 2012 a hybrid electronic medical registry (HEMR) was introduced to capture routine data and to generate reports on morbidity and mortality. This paper reviews our experience in setting up a metropolitan MMC and compares the quality of the reported morbidity data from the pre- and post-HEMR era.Methods. We compared data from the MMC before and after the introduction of the HEMR to audit the impact of these meetings on the reporting and analysis of surgical morbidity and mortality in our service.Results. During the 4-year period from 2008 to 2011, a total of 208 MMCs were held. A total of 10 682 patients were admitted by the PMTS during that period, of whom 87% were males, and the mean age was 26 years. Penetrating trauma accounted for 40.9% (4 344/10 628) of the total workload. A total of 432 (4.1%) morbidities were identified. Of these, 36.6% (158) were related to human error, 32% (138/432) were related to surgical pathologies and the remaining 31.9%  (136/432) were related to systemic diseases. There was an exponential increase in the reporting of morbidity each year. The total in-hospital mortality was 3% (358/10 682). Following the introduction of the HEMR, from 2012 to 2014, 6 217 patients were admitted. A total of 1 314 (21.1%) adverse events and 315 (5.1%) deaths were recorded by the HEMR. The adverse events were divided into 875 ‘pathology-related’ morbidities and 439 ‘error-related’ morbidities.Conclusions. The development of the MMC led to increased reporting of morbidity and mortality. The introduction of the HEMR resulted in a dramatic improvement in the capturing of morbidity and mortality data, suggesting that a paper-based  self-reporting system tends to underestimate morbidity. Over one-third of all  morbidities were related to human error. Common morbidities have been identified

Hanging-related injury in Pietermaritzburg, South Africa

BACKGROUND: Hanging is a common form of self-harm, and emergency care physicians will not infrequently be called upon to manage a survivor.Despite the relative frequency of the injury, there is a paucity of literature on the topic and the spectrum and incidence of associated injuries are poorly described. OBJECTIVES: To review experience with management of victims of hanging at a major trauma centre in South Africa. METHODS: All patients treated by the Pietermaritzburg Metropolitan Trauma Service following a hanging incident between December 2012 and December 2018 were identified from the Hybrid Electronic Medical Registry. Basic demographics were recorded, and the management and outcome of each patient were noted. RESULTS: During the 6-year period under review, a total of 154 patients were seen following a hanging incident. The mean age was 29.4 years. There were 24 females (15.6%) and 130 males (84.4%). The vast majority (n=150; 97.5%) had attempted suicide, and only 4 hangings (2.5%) were accidental. A total of 92 patients (60.9%) had consumed alcohol prior to the incident. There were 23 patients with a Glasgow Coma Score (GCS) 12 (mild TBI). A total of 7 patients (4.5%) required intensive care unit admission, and 25 (16.2%) required intubation. The following extracranial injuries were documented on computed tomography scans: hyoid bone fractures (n=2), cervical spine fracture (n=10), mandible fracture (n=4) and oesophageal injury (n=1). Intracranial pathology was evident on 27.0% of scans, with the most common finding being global cerebral ischaemia. The mortality rate was 2.5% (4/154). CONCLUSIONS: Hanging is a common mechanism of self-harm. It is associated with significant injuries and mortality. The acute management of hanging should focus on airway protection followed by detailed imaging of the head and neck. Further work must attempt to include mortuary data on hanging

Discrepancy in clinical outcomes of patients with gunshot wounds in car hijacking: a South African experience

INTRODUCTION: Discrepancy in outcomes between urban and rural trauma patients is well known. We reviewed our institutional experience with the management of gunshot wounds (GSWs) in the specific setting of car hijacking and focused on clinical outcome between rural and urban patients. METHODS: A retrospective review was conducted at a major trauma centre in South Africa over an 8-year period for all patients who presented with any form of GSWs in car hijacking settings. Specific clinical outcomes were compared between rural and urban patients. RESULTS: A total of 101 patients were included (74% male, mean age 34 years). Fifty-five per cent were injured in rural areas and the remaining 45% (45/101) were in the urban district. Mean time from injury to arrival at our trauma centre was 11 hours for rural and 4 hours for urban patients (p < 0.001). Seventy-six per cent (76/101) sustained GSWs to multiple body regions. Sixty-three of the 101 (62%) patients required one or more operative interventions. In individual logistic regressions adjusted for sex and number of regions injured, rural patients were 9 (95% CI: 1.9-44.4) and 7 (95% CI: 2.124.5) times more likely than urban patients to have morbidities or required admissions to intensive care respectively. The risk of death in rural patients was 36 (95% CI: 4.5-284.6) times higher than that of urban patients. CONCLUSIONS: Patients who sustained GSWs in carjacking incidents that occurred in rural areas are associated with significantly greater morbidity and mortality compared with their urban counterparts. Delay to definitive care is likely to be the significant contributory factor, and improvement in prehospital emergency medical service is likely to be beneficial in improving patient outcome

A review of blunt pelvic injuries at a major trauma centre in South Africa.

BACKGROUND: The collective five-year experience with the acute management of pelvic trauma at a busy South African trauma service is reviewed to compare the usefulness and applicability of current grading systems of pelvic trauma and to review the compliance with current guidelines regarding pelvic binder application during the acute phase of resuscitation. METHODS: A retrospective review was conducted over a 5-year period from December 2012 to December 2017 on all polytrauma patients who presented with a pelvic fracture. Mechanism of injury and presenting physiology and clinical course including pelvic binder application were documented. Pelvic fractures were graded according to the Young- Burgess and Tile systems. RESULTS: There was a cohort of 129 patients for analysis. Eighty-one were male and 48 female with a mean age was 33.6 ± 13.1 years. Motor vehicle-related collisions (MVCs) were the main mechanism of injury (50.33%) and pedestrian vehicle collisions (PVCs) were the second most common (37.98%). The most common associated injuries were abdominal injuries (41%), chest injury (37%), femur fractures (21%), tibia fractures (15%) and humerus fracture (14.7%). Thirty patients in this cohort (23%) underwent a laparotomy. They were mainly in the Tile B (70%) and lateral compression (63%) groups. Nine patients underwent pelvic pre-peritoneal packing. Thirty-five (27%) patients were admitted to ICU. Fifteen (12%) patients died. The Young-Burgess classification had a greater accuracy in predicting death than the Tile classification. Forty per cent of deaths occurred in ICU, 33% died secondary to a traumatic brain injury (TBI). Twenty per cent died in casualty and 6.6% in the operating room from ongoing haemorrhage. A pelvic binder was not applied in 66% of patients. In the 34% of patients who had a pelvic binder applied, it was applied post CT scan in 24.8%, in the pre-hospital setting in 7.2%, and on arrival in 2.4% of patients. In 73% of deaths, a binder was not applied, and of those deaths, 54% showed signs of haemodynamic instability. CONCLUSION: It would appear that our application of pelvic binders in patients with acute pelvic trauma is ad hoc. Appropriate selection of patients, who may benefit from a binder and it's timely application, has the potential to improve outcome in these patients

Charring rate for fire exposed X-Lam

Design of timber structures has been outlined in Eurocode 5. Notional charring rate for softwood and hardwood timber is given. For the performance of X-LAM panels in fire, only little information on charring is available and whether the fire behaviour of X-LAM is similar to homogenous timber panels has not yet been systematically analysed. This paper presents an overview of fire performance of X-LAM and evaluation of its resistance to elevated temperature as an element of structure in comparison to homogeneous timber panels. Numerical study has been carried out based on available experimental results. Charring rates for X-LAM panels obtained from experimental results are compared with those obtained from Eurocode 5 and proposed simplified model

Solution Structures of the Acyl Carrier Protein Domain from the Highly Reducing Type I Iterative Polyketide Synthase CalE8

Biosynthesis of the enediyne natural product calicheamicins γ1I in Micromonospora echinospora ssp. calichensis is initiated by the iterative polyketide synthase (PKS) CalE8. Recent studies showed that CalE8 produces highly conjugated polyenes as potential biosynthetic intermediates and thus belongs to a family of highly-reducing (HR) type I iterative PKSs. We have determined the NMR structure of the ACP domain (meACP) of CalE8, which represents the first structure of a HR type I iterative PKS ACP domain. Featured by a distinct hydrophobic patch and a glutamate-residue rich acidic patch, meACP adopts a twisted three-helix bundle structure rather than the canonical four-helix bundle structure. The so-called ‘recognition helix’ (α2) of meACP is less negatively charged than the typical type II ACPs. Although loop-2 exhibits greater conformational mobility than other regions of the protein with a missing short helix that can be observed in most ACPs, two bulky non-polar residues (Met992, Phe996) from loop-2 packed against the hydrophobic protein core seem to restrict large movement of the loop and impede the opening of the hydrophobic pocket for sequestering the acyl chains. NMR studies of the hydroxybutyryl- and octanoyl-meACP confirm that meACP is unable to sequester the hydrophobic chains in a well-defined central cavity. Instead, meACP seems to interact with the octanoyl tail through a distinct hydrophobic patch without involving large conformational change of loop-2. NMR titration study of the interaction between meACP and the cognate thioesterase partner CalE7 further suggests that their interaction is likely through the binding of CalE7 to the meACP-tethered polyene moiety rather than direct specific protein-protein interaction

1A6/DRIM, a Novel t-UTP, Activates RNA Polymerase I Transcription and Promotes Cell Proliferation

BACKGROUND: Ribosome biogenesis is required for protein synthesis and cell proliferation. Ribosome subunits are assembled in the nucleolus following transcription of a 47S ribosome RNA precursor by RNA polymerase I and rRNA processing to produce mature 18S, 28S and 5.8S rRNAs. The 18S rRNA is incorporated into the ribosomal small subunit, whereas the 28S and 5.8S rRNAs are incorporated into the ribosomal large subunit. Pol I transcription and rRNA processing are coordinated processes and this coordination has been demonstrated to be mediated by a subset of U3 proteins known as t-UTPs. Up to date, five t-UTPs have been identified in humans but the mechanism(s) that function in the t-UTP(s) activation of Pol I remain unknown. In this study we have identified 1A6/DRIM, which was identified as UTP20 in our previous study, as a t-UTP. In the present study, we investigated the function and mechanism of 1A6/DRIM in Pol I transcription. METHODOLOGY/PRINCIPAL FINDINGS: Knockdown of 1A6/DRIM by siRNA resulted in a decreased 47S pre-rRNA level as determined by Northern blotting. Ectopic expression of 1A6/DRIM activated and knockdown of 1A6/DRIM inhibited the human rDNA promoter as evaluated with luciferase reporter. Chromatin immunoprecipitation (ChIP) experiments showed that 1A6/DRIM bound UBF and the rDNA promoter. Re-ChIP assay showed that 1A6/DRIM interacts with UBF at the rDNA promoter. Immunoprecipitation confirmed the interaction between 1A6/DRIM and the nucleolar acetyl-transferase hALP. It is of note that knockdown of 1A6/DRIM dramatically inhibited UBF acetylation. A finding of significance was that 1A6/DRIM depletion, as a kind of nucleolar stress, caused an increase in p53 level and inhibited cell proliferation by arresting cells at G1. CONCLUSIONS: We identify 1A6/DRIM as a novel t-UTP. Our results suggest that 1A6/DRIM activates Pol I transcription most likely by associating with both hALP and UBF and thereby affecting the acetylation of UBF

Brain Derived Neurotrophic Factor (BDNF) Expression Is Regulated by MicroRNAs miR-26a and miR-26b Allele-Specific Binding

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an essential role in neuronal development and plasticity. MicroRNA (miRNAs) are small non-coding RNAs of about 22-nucleotides in length regulating gene expression at post-transcriptional level. In this study we explore the role of miRNAs as post-transcriptional inhibitors of BDNF and the effect of 3′UTR sequence variations on miRNAs binding capacity. Using an in silico approach we identified a group of miRNAs putatively regulating BDNF expression and binding to BDNF 3′UTR polymorphic sequences. Luciferase assays demonstrated that these miRNAs (miR-26a1/2 and miR-26b) downregulates BDNF expression and that the presence of the variant alleles of two single nucleotide polymorphisms (rs11030100 and rs11030099) mapping in BDNF 3′UTR specifically abrogates miRNAs targeting. Furthermore we found a high linkage disequilibrium rate between rs11030100, rs11030099 and the non-synonymous coding variant rs6265 (Val66Met), which modulates BDNF mRNA localization and protein intracellular trafficking. Such observation led to hypothesize that miR-26s mediated regulation could extend to rs6265 leading to an allelic imbalance with potentially functional effects, such as peptide's localization and activity-dependent secretion. Since rs6265 has been previously implicated in various neuropsychiatric disorders, we evaluated the distribution of rs11030100, rs11030099 and rs6265 both in a control and schizophrenic group, but no significant difference in allele frequencies emerged. In conclusion, in the present study we identified two novel miRNAs regulating BDNF expression and the first BDNF 3′UTR functional variants altering miRNAs-BDNF binding

Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance