Management and birth outcomes of pregnant women with Chiari malformations : a 14 years retrospective case series

Objective The management of Chiari malformations in pregnancy is challenging due to the perceived risk of adverse maternal neurological outcomes and raising intracranial pressure during labour. Our aim was to evaluate the management and health outcomes of pregnant women cared for at a regional referral center and highlight elements of best practice. Study Design A retrospective case series of all pregnant women diagnosed with Chiari malformation over fourteen years (January 2004- June 2018) at the Birmingham Women’s Hospital – UK. Results Twenty-one women (23 pregnancies) with Chiari malformation were included, four had syringomyelia (4/21,19%) and six had previously undergone craniovertebral decompression (6/21, 29%). The median age was 34-years (range 20-41), the median gravidity was two (range 1-8), the median parity was one (range 0-6), and the median extent of tonsillar herniation was 11 mm (range 9-18). The majority of women received their preferred mode of delivery (15 normal vaginal deliveries (15/23, 65.2%) and 6 elective Caesarean sections (6/23, 26.1%)) with two pregnancies ending with an emergency caesarean section for obstetric complications (2/23, 8.7%). Five Caesarean section were performed under general anaesthetic, two under spinal (2/23, 8.7%) and one under epidural anaesthesia (1/23, 4.3%) with no neurological sequelae. There were no adverse neurological outcomes at discharge postnatally. Conclusions Offering normal vaginal delivery with effective analgesia, for women with Chiari malformation, appears to be safe. Pregnancy care should be provided by a multi-disciplinary team with experience in managing Chiari malformation

Isolated rectal buttonhole tears in obstetrics: case series and review of the literature.

INTRODUCTION AND HYPOTHESIS: The management of isolated rectal buttonhole tears is not standardised and can be challenging in an acute obstetric setting. Our aim was to review the published literature and describe management and repair techniques in a case series. METHODS: A literature search was carried out. All results were screened and reviewed. Rectal buttonhole tears following vaginal delivery between April 2012 and January 2020 in our institution were identified. Repair technique and post-operative management were recorded. RESULTS: There were nine published case reports (four instrumental deliveries, two vaginal breech and three normal vaginal deliveries). Four case reports described a two-layer closure and five described a three-layer closure. Two cases were repaired in collaboration with colorectal surgeons. All nine cases made an uneventful recovery. We identified three patients with buttonhole tears all of whom had instrumental deliveries. A colorectal surgeon repaired the tear in two layers in one case, and an obstetrician performed the repair in the other two cases, one in three layers and the other in two layers. One patient had a de-functioning stoma at a later date due to a second breakdown of the recto-vaginal fistula repair. CONCLUSION: Buttonhole tears are rare but techniques of repair vary. Most cases reviewed had an uneventful recovery after repair. We provide standardised steps for repair and management of isolated rectal buttonhole tears along with a video demonstrating the repair technique in an animal tissue (pig) model

Review of available national guidelines for obstetric anal sphincter injury.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injuries (OASIs) are the most severe form of perineal trauma with potentially devastating effects on a mother's quality of life. There are various national guidelines available for their management. The aim of this study was to review and compare recommendations from published national guidelines regarding management and prevention of OASI. METHODS: We searched the PUBMED, EMBASE, MEDLINE, CINAHL and COCHRANE databases from January 2008 till October 2019 using relevant Medical Subject Headings (MeSH), including all subheadings. The guideline characteristics were mapped and methodological quality assessed with the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool by three independent reviewers. To compare the methodological quality of the guidelines, the interpretation of the six domain scores were taken into consideration. By consensus of the authors, a score of 70% was taken as a cut-off, and scores above this were considered 'high quality'. RESULTS: Thirteen national guidelines on perineal trauma were included and analysed. Nine of these were specific to OASI. There is wide variation in methodological quality and evidence used for recommendations. AGREE scores for overall guideline assessment were > 70% in eight of the guidelines, with Australia-Queensland, Canada, the UK and USA scoring highest. CONCLUSIONS: The wide variation in methodological quality and evidence used for recommendations suggests that there is a need for an agreed international guideline. This will enable healthcare practitioners to follow the same recommendations, with the most recent evidence, and provide evidence-based care to all women globally

Ocean Acidification at High Latitudes: Potential Effects on Functioning of the Antarctic Bivalve Laternula elliptica

Ocean acidification is a well recognised threat to marine ecosystems. High latitude regions are predicted to be particularly affected due to cold waters and naturally low carbonate saturation levels. This is of concern for organisms utilising calcium carbonate (CaCO3) to generate shells or skeletons. Studies of potential effects of future levels of pCO2 on high latitude calcifiers are at present limited, and there is little understanding of their potential to acclimate to these changes. We describe a laboratory experiment to compare physiological and metabolic responses of a key benthic bivalve, Laternula elliptica, at pCO2 levels of their natural environment (430 µatm, pH 7.99; based on field measurements) with those predicted for 2100 (735 µatm, pH 7.78) and glacial levels (187 µatm, pH 8.32). Adult L. elliptica basal metabolism (oxygen consumption rates) and heat shock protein HSP70 gene expression levels increased in response both to lowering and elevation of pH. Expression of chitin synthase (CHS), a key enzyme involved in synthesis of bivalve shells, was significantly up-regulated in individuals at pH 7.78, indicating L. elliptica were working harder to calcify in seawater undersaturated in aragonite (ΩAr = 0.71), the CaCO3 polymorph of which their shells are comprised. The different response variables were influenced by pH in differing ways, highlighting the importance of assessing a variety of factors to determine the likely impact of pH change. In combination, the results indicate a negative effect of ocean acidification on whole-organism functioning of L. elliptica over relatively short terms (weeks-months) that may be energetically difficult to maintain over longer time periods. Importantly, however, the observed changes in L. elliptica CHS gene expression provides evidence for biological control over the shell formation process, which may enable some degree of adaptation or acclimation to future ocean acidification scenarios

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

Clinical practice variation and need for pediatric-specific treatment guidelines among rheumatologists caring for children with ANCA-associated vasculitis: an international clinician survey

Background: Because pediatric antineutrophil cytoplasmic antibody-associated vasculitis is rare, management generally relies on adult data. We assessed treatment practices, uptake of existing clinical assessment tools, and interest in pediatric treatment protocols among rheumatologists caring for children with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Methods: A needs-assessment survey developed by an international working group of pediatric rheumatologists and two nephrologists was circulated internationally. Data were summarized with descriptive statistics. Pearson’s chi-square tests were used in inferential univariate analyses. Results: The 209 respondents from 36 countries had collectively seen ~1600 children with GPA/MPA; 144 had seen more than two in the preceding 5 years. Standardized and validated clinical assessment tools to score disease severity, activity, and damage were used by 59, 63, and 36%, respectively; barriers to use included lack of knowledge and limited perceived utility. Therapy varied significantly: use of rituximab rather than cyclophosphamide was more common among respondents from the USA (OR = 2.7 [1.3-5.5], p = 0.0190, n = 139), those with >5 years of independent practice experience (OR = 3.8 [1.3-12.5], p = 0.0279, n = 137), and those who had seen >10 children with GPA/MPA in their careers (OR = 4.39 [2.1-9.1], p = 0.0011, n = 133). Respondents who had treated >10 patients were also more likely to continue maintenance therapy for at least 24 months (OR = 3.0 [1.4-6.4], p = 0.0161, n = 127). Ninety six percent of respondents believed in a need for pediatric-specific treatment guidelines; 46% supported adaptation of adult guidelines while 69% favoured guidelines providing a limited range of treatment options to allow comparison of effectiveness through a registry. Conclusions: These data provide a rationale for developing pediatric-specific consensus treatment guidelines for GPA/MPA. While pediatric rheumatologist uptake of existing clinical tools has been limited, guideline uptake may be enhanced if outcomes of consensus-derived treatment options are evaluated within the framework of an international registry.Medicine, Faculty ofNon UBCMedicine, Department ofPediatrics, Department ofRheumatology, Division ofReviewedFacult