Engaging surgeons among clinician-scientists.

Since completion of the Human Genome Project at the turn of the century, there have been significant advances in genomic technologies together with genomics research. At the same time, the gap between biomedical discovery and clinical application has narrowed through translational medicine, so establishing the era of personalised medicine. In bridging these two disciplines, the clinician-scientist has become an integral part of modern practice. Surgeons and surgical diseases have been less represented than physicians and medical conditions among clinician-scientists and research. Here, we explore the possible reasons for this and propose strategies for moving forward. Discovery-driven personalised medicine is both the present and the future of clinical patient care worldwide, and South Africa is uniquely placed to build capacity for biomedical discovery in Africa. Diverse engagement across clinical disciplines, including surgery, is necessary in order to integrate modern medicine into a developing-world contextualised perspective.

A long-term follow-up study of spinal abnormalities and pain in adults with cerebral palsy and spastic diplegia more than 25 years after selective dorsal rhizotomy.

OBJECTIVE: The main purpose of selective dorsal rhizotomy (SDR) is to reduce spasticity in the lower extremities of children diagnosed with cerebral palsy (CP) and spastic diplegia. The potential for developing spinal abnormalities and pain is a concern, especially in the aging CP population. Therefore, the aim of this study was to evaluate spinal abnormalities, level of pain, and disability (due to back or leg pain) in adults with CP, and associations with participant characteristics, more than 25 years after SDR. METHODS: This is a 9-year follow-up study with data collection conducted in 2008 and 2017. Radiographs were assessed for the degree of scoliosis, thoracic kyphosis and lumbar lordosis curvatures, and prevalence of spondylolysis and spondylolisthesis, while level of pain and disability was determined with a self-developed questionnaire and the Oswestry Disability Index (ODI) questionnaire, respectively. RESULTS: Twenty-five participants were included (15 males; median age 35.9 years, IQR 34.3-41.5 years), with a follow-up time after SDR ranging from 25 to 35 years. No clinically relevant changes were found for spinal curvatures, spondylolysis and spondylolisthesis, perceived pain frequency, and ODI scores between 2008 and 2017. While the prevalence of spondylolysis was 44%, spondylolisthesis was found in 20% (of whom 15% were grade I and 5% grade II), lumbar hyperlordosis was found in 32%, thoracic hyperkyphosis in 4%, and scoliosis in 20%. The Cobb angle was < 25°, and no patient required surgery for scoliosis. In addition, the low back was reported as the most common site of pain, with 28% of the adults with CP having daily pain. This resulted in 80% of the cohort indicating none or minimal disability due to pain based on the ODI. The only correlation found was between hyperkyphosis and female gender. CONCLUSIONS: At follow-up more than 25 years after SDR, no progression in spinal abnormalities, level of pain, and disability was found when compared with findings 15 years after SDR. The prevalence of scoliosis, thoracic hyperkyphosis, and lumbar hyperlordosis was within the range reported for adults with CP, while spondylolysis and spondylolisthesis occurred more often than would be expected. It is difficult, however, to establish the role of SDR in this finding, given the limited data on the natural history of CP. Despite the encouraging outcome of this long-term follow-up study after SDR, it is important to continue monitoring adults with CP during the aging process.

Ventriculoperitoneal shunt insertion in human immunodeficiency virus infected adults: a systematic review and meta-analysis.

BACKGROUND: Hydrocephalus is a common, life threatening complication of human immunodeficiency virus (HIV)-related central nervous system opportunistic infection which can be treated by insertion of a ventriculoperitoneal shunt (VPS). In HIV-infected patients there is concern that VPS might be associated with unacceptably high mortality. To identify prognostic indicators, we aimed to compare survival and clinical outcome following VPS placement between all studied causes of hydrocephalus in HIV infected patients. METHODS: The following electronic databases were searched: The Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), EMBASE, CINAHL Plus, LILACS, Research Registry, the metaRegister of Controlled Trials, ClinicalTrials.gov, African Journals Online, and the OpenGrey database. We included observational studies of HIV-infected patients treated with VPS which reported of survival or clinical outcome. Data was extracted using standardised proformas. Risk of bias was assessed using validated domain-based tools. RESULTS: Seven Hunderd twenty-three unique study records were screened. Nine observational studies were included. Three included a total of 75 patients with tuberculous meningitis (TBM) and six included a total of 49 patients with cryptococcal meningitis (CM). All of the CM and two of the TBM studies were of weak quality. One of the TBM studies was of moderate quality. One-month mortality ranged from 62.5-100% for CM and 33.3-61.9% for TBM. These pooled data were of low to very-low quality and was inadequate to support meta-analysis between aetiologies. Pooling of results from two studies with a total of 77 participants indicated that HIV-infected patients with TBM had higher risk of one-month mortality compared with HIV non-infected controls (odds ratio 3.03; 95% confidence-interval 1.13-8.12; p = 0.03). CONCLUSIONS: The evidence base is currently inadequate to inform prognostication in VPS insertion in HIV-infected patients. A population-based prospective cohort study is required to address this, in the first instance.

Transient Incomplete Locked-In Syndrome Secondary to Supratentorial Gunshot Wound.

BACKGROUND: Locked-in syndrome (LIS) is a rare neurologic disorder characterized as quadriplegia with anarthria. The diagnosis of LIS is challenging and requires a high index of suspicion. The syndrome is typically caused by an infratentorial lesion to the ventral pons, regardless of etiology. LIS secondary to supratentorial injury is extremely rare, and to our knowledge, this is the first reported case. CASE DESCRIPTION: We report the case of a 26-year-old woman who sustained a gunshot to the left suboccipital area, with supratentorial extension. A diagnosis of incomplete LIS was made on the day of admission, with eye movement preservation. Imaging studies confirmed bilateral injury of the motor homunculus. The clinical course was that of progressive improvement, aided by intensive care unit (ICU) supportive care and early physiotherapy rehabilitation. Her condition improved, and she was discharged to a rehabilitation facility at the end of week 7 postadmission. CONCLUSIONS: This is a unique case of incomplete LIS after supratentorial injury. Initial ICU care and early rehabilitation likely played a major role in the full recovery of this patient. The influence of etiology and site of injury on outcome prognosis is also suggested. Although severe diffuse brain injury may occur in the face of an unremarkable computed tomography (CT) scan, the emerging role of magnetic resonance imaging in optimally evaluating traumatic brain injury with discordant clinical and CT information is highlighted and is useful in cases of LIS where prognosis prediction is important.

A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure.

Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient's liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions. The methodology has been designed to meet specifications for GMP production, required for manufacture of advanced therapy medicinal products (ATMPs). In a porcine model of severe liver failure, damage was assured in all animals by surgical ischaemia in pigs with human sized livers (1.2-1.6 kg liver weights). The BioArtificial liver (UCLBAL) improved important prognostic clinical liver-related parameters, eg, a significant improvement in coagulation, reduction in vasopressor requirements, improvement in blood pH and in parameters of intracranial pressure (ICP) and oxygenation.

Ventriculoperitoneal shunt insertion for hydrocephalus in human immunodeficiency virus-infected adults: a systematic review and meta-analysis protocol.

BACKGROUND: Hydrocephalus is a recognised complication of human immunodeficiency virus (HIV)-related opportunistic infections. Symptomatic raised cerebrospinal fluid pressure can be treated with ventriculoperitoneal shunt insertion (VPS). In HIV-infected patients however, there is a concern that VPS might be associated with unacceptably high rates of mortality. We aim to systematically review and appraise published literature to determine reported outcomes and identify predictors of outcome following VPS in relevant subgroups of HIV-infected adults. METHODS: The following electronic databases will be searched: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, CINAHL (EBSCOhost), LILACS (BIREME), Research Registry ( www.researchregistry.com ), the metaRegister of Controlled Trials (mRCT) ( www.controlled-trials.com ), ClinicalTrials.gov ( www.clinicaltrials.gov ) and OpenSIGLE database. Any randomised studies, cohort studies, case-control studies, interrupted time series or sequential case series reporting survival following VPS in HIV-infected individuals will be included. If high-quality homogenous studies exist, meta-analysis will be conducted to determine 1-, 6- and 12-month mortality with comparison made between underlying aetiologies of hydrocephalus. DISCUSSION AND CONCLUSION: This study will generate a comprehensive review of VPS in HIV-infected patients for publication. The primary outcome of meta-analysis is 12-month survival. If only low-quality, heterogeneous studies are available, this study will demonstrate this deficiency and will be of value in justifying and aiding the design of future studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016052239.

Targeted treatment in severe traumatic brain injury in the age of precision medicine.

In recent years, much progress has been made in our understanding of traumatic brain injury (TBI). Clinical outcomes have progressively improved, but evidence-based guidelines for how we manage patients remain surprisingly weak. The problem is that the many interventions and strategies that have been investigated in randomized controlled trials have all disappointed. These include many concepts that had become standard care in TBI. And that is just for adult TBI; in children, the situation is even worse. Not only is pediatric care more difficult than adult care because physiological norms change with age, but also there is less evidence for clinical practice. In this article, we discuss the heterogeneity inherent in TBI and why so many clinical trials have failed. We submit that a key goal for the future is to appreciate important clinical differences between patients in their pathophysiology and their responses to treatment. The challenge that faces us is how to rationally apply therapies based on the specific needs of an individual patient. In doing so, we may be able to apply the principles of precision medicine approaches to the patients we treat.

Delayed massive epistaxis from traumatic cavernous carotid false aneurysms: A report of two unusual cases.

Introduction Blunt head trauma can injure the cavernous segment of the internal carotid artery (ICA). This may result in a carotid cavernous fistula (CCF). Rarely, a traumatic aneurysm may bleed medially causing massive epistaxis. Case presentation We present two cases of traumatic intracavernous carotid pseudoaneurysms with delayed massive epistaxis. The patients were managed with endovascular treatment involving coil embolization with parent vessel sparing and detachable balloon occlusion with carotid sacrifice. Early clinical outcome was good in both patients. Wherever possible, the CARE1 guidelines were followed in the reporting. Conclusion These cases illustrate the delayed nature of traumatic aneurysms and the need for a high index of suspicion in the presence of skull base fractures. The use of endovascular detachable balloon occlusion and coil embolization treatment with parent vessel preservation is shown.