Severe head injuries in children

The aim of this dissertation is to review the current literature on severe head injuries in children, with particular respect to epidemiology, clinical features and investigation, pathophysiology, management and outcome. In addition a retrospective study was carried out on severe head injuries at Red Cross War Memorial Children's Hospital. Finally, the findings of this study are discussed in the light of the experience of other neurosurgical and trauma centres. In this way similarities as well as features peculiar to our setting can be identified with the aim of improving the understanding and management of severe head injuries in children in the Western Cape

Pituitary apoplexy : can histopathology, radiological imaging and predisposing factors be used in predicting outcome?

Includes abstract.Includes bibliographical references (leaves 98-112).Pituitary apoplexy is an uncommon, yet potentially fatal illness, usually the result of infarction, hemorrhage or a combination of both in a pituitary tumor. The management of pituitary apoplexy consists of replacement therapy and in the majority of patients, surgical decompression, although some cases may be treated conservatively. Up to now no study has attempted to separate the two histopathological types of pituitary apoplexy or to analyze their clinical and radiological significance on presentation and outcome

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Pituitary Metastases. Metastases de la Glande Pituitaire (English )

Introduction Metastatic disease of the pituitary is an uncommon clinical problem, although autopsy findings on patients who die of disseminated carcinoma suggest that it occurs more frequently than is clinically evident. Pituitary metastases are often difficult to distinguish from pituitary adenomas both clinically and radiologically. Materials and Methods: Between 1967 and 2001 six patients with histologically proven pituitary metastases were treated surgically by the Division of Neurosurgery at Groote Schuur Hospital. Results The mean age of patients was 55.5 years. Four patients had carcinoma of the lung, 1 of the breast and 1 ‘epithelial\'. Clinical presentation included headaches (3 patients), visual deficits (4 patients) and ophthalmoplegia (3 patients). No endocrine dysfunction was found. Radiological investigation was non-specific. The patients all had palliative improvement following surgery but the prognosis was poor with an average survival of 7 months. Conclusion Pituitary metastasis is an uncommon diagnosis, the most common primary cancers being breast and lung. The clinical and radiological diagnosis is usually non-specific although diabetes insipidus in a patient with a known malignancy may raise the suspicion. The treatment whether surgical or radiotherapy offers good palliation of symptoms, but the outcome is determined by the metastatic disease and is poor. Résumé Introduction Les métastases de la glande pituitaire sont peu fréquents, même si les résultats d\'autopsies pratiquées sur des patients décédés des suites de carcinomes généralisés suggèrent qu\'elles sont moins rares que leur expression clinique ne l\'indique. Les métastases pituitaires sont souvent difficiles à distinguer des adénomes hypophysaires, tant du point de vue clinique que radiologique. Matériel et méthodes De 1967 à 2001, six patients atteints de métastases pituitaires, confirmées par des examens histologiques, ont bénéficié d\'un traitement chirurgical dans le service de neurochirurgie de l\'hôpital de Groote Schuur, Le Cap. Résultats La moyenne d\'âge des patients était de 55.5 ans. Quatre d\'entre eux présentaient des carcinomes du poumon, un du sein et un « épithélial ». Les symptômes cliniques étaient les suivants : céphalées (3 patients), déficits visuels (4 patients) et ophtalmoplégie (3 patients). Aucun trouble endocrinien n\'avait été constaté. Les examens radiologiques avaient été non spécifiques. Dans tous les cas, les procédures chirurgicales ont entraîné des améliorations palliatives, mais le pronostic vital était toujours médiocre puisque le décès est survenu en moyenne 7 mois plus tard. Conclusion Les métastases pituitaires constituent un diagnostic rare. Les cancers du poumon et du sein étant les origines primitives les plus fréquents. Habituellement, le diagnostic clinique et radiologique est non spécifique, bien qu\'un diabète insipide chez un patient souffrant d\'une maladie maligne puisse éveiller les soupçons. Les deux formes de traitement (chirurgie ou radiothérapie) représentent de bons moyens palliatifs au niveau des symptômes . Toutefois, l\'issue, fonction du degré métastatique, est généralement fatale. (Af. J. of Neurological Sciences: 2003 22(1)

Cerebellar Haemangioblastoma in Pregnancy: A Report of 2 Cases Suggesting Accelerated Growth Les Hemangioblastomes Cerebelleux : a Propos de 2 Cas Suggerant Une Acceleration de Leur Developpement Durant la Grossesse (English)

Haemangioblastoma is a relatively uncommon vascular tumour, usually occurring in the cerebellum. Twenty-eight cases of cerebellar haemangioblastoma in pregnancy have previously been described in the literature. It has been suggested that the hormonal and vascular changes of pregnancy have been associated with accelerated growth and symptomatology. We present two patients with haemangioblastoma, whose growth and vascularity during pregnancy support this view. Résumé Les hémangioblastomes sont des tumeurs relativement peu fréquentes, intéressant le cervelet. La littérature fait état de vingt-huit cas d\'hémangioblastomes apparus durant la grossesse. Il a été suggéré que l\'accélération de leur développement et de la symptomatologie étaient liées aux changements hormonaux et vasculaires associés à la grossesse. Nous rapportons deux cas de patientes atteintes d\'hémangioblastome dont le développement et la vascularisation durant la grossesse corroborent ce point de vue. (Af. J. Neurological Sciences: 2003 22(2)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease