Highly integrated workflows for exploring cardiovascular conditions: Exemplars of precision medicine in Alzheimer's disease and aortic dissection.

For precision medicine to be implemented through the lens of in silico technology, it is imperative that biophysical research workflows offer insight into treatments that are specific to a particular illness and to a particular subject. The boundaries of precision medicine can be extended using multiscale, biophysics-centred workflows that consider the fundamental underpinnings of the constituents of cells and tissues and their dynamic environments. Utilising numerical techniques that can capture the broad spectrum of biological flows within complex, deformable and permeable organs and tissues is of paramount importance when considering the core prerequisites of any state-of-the-art precision medicine pipeline. In this work, a succinct breakdown of two precision medicine pipelines developed within two Virtual Physiological Human (VPH) projects are given. The first workflow is targeted on the trajectory of Alzheimer's Disease, and caters for novel hypothesis testing through a multicompartmental poroelastic model which is integrated with a high throughput imaging workflow and subject-specific blood flow variability model. The second workflow gives rise to the patient specific exploration of Aortic Dissections via a multi-scale and compliant model, harnessing imaging, computational fluid-dynamics (CFD) and dynamic boundary conditions. Results relating to the first workflow include some core outputs of the multiporoelastic modelling framework, and the representation of peri-arterial swelling and peri-venous drainage solution fields. The latter solution fields were statistically analysed for a cohort of thirty-five subjects (stratified with respect to disease status, gender and activity level). The second workflow allowed for a better understanding of complex aortic dissection cases utilising both a rigid-wall model informed by minimal and clinically common datasets as well as a moving-wall model informed by rich datasets.

'What gets measured gets managed': revisiting the indicators for maternal and newborn health programmes.

BACKGROUND: The health of women and children are critical for global development. The Sustainable Development Goals (SDG) agenda and the Global Strategy for Women's, Children's, and Adolescent's Health 2016-2030 aim to reduce maternal and newborn deaths, disability, and enhancement of well-being. However, information and data on measuring countries' progress are limited given the variety of methodological challenges of measuring care around the time of birth, when most maternal and neonatal deaths and morbidities occur. MAIN BODY: In 2015, the World Health Organization launched Mother and Newborn Information for Tracking Outcomes and Results (MoNITOR), a technical advisory group to WHO. MoNITOR comprises 14 independent global experts from a variety of disciplines selected in a competitive process for their technical expertise and regional representation. MoNITOR will provide technical guidance to WHO to ensure harmonized guidance, messages, and tools so that countries can collect useful data to track progress toward achieving the Sustainable Development Goals. SHORT CONCLUSION: Ultimately, MoNITOR will provide technical guidance to WHO to ensure harmonized guidance, messages, and tools so that countries can collect useful data to track progress toward achieving the Sustainable Development Goals.

Sonographic evaluation of immobility of normal and endometriotic ovary in detection of deep endometriosis.

OBJECTIVES: To examine the association between ovarian immobility and presence of endometriomas and assess the diagnostic accuracy of transvaginal sonographic (TVS) ovarian immobility in the detection of deep infiltrating endometriosis (DIE). METHODS: This was a multicenter prospective observational study of women presenting with chronic pelvic pain from January 2009 to March 2015. Women with or without history of endometriosis who were scheduled to undergo laparoscopic surgery for endometriosis gave a detailed history and underwent specialized TVS in a tertiary referral unit prior to laparoscopy. During TVS, ovarian mobility and the presence of endometriomas were assessed. The relationship between TVS ovarian mobility, with or without endometriomas, and DIE was correlated with the gold standard, diagnosis of endometriosis at laparoscopy. RESULTS: Included in the analysis were 265 women with preoperative TVS and laparoscopic outcomes. Ovarian immobility on TVS was significantly associated with presence of endometriomas at surgery, with a prevalence of 12.2%, 10.8% and 52.7% for fixation of the left ovary only, the right ovary only and bilateral ovaries, respectively, compared with 4.2%, 3.7% and 7.3% for normal ovaries. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and positive and negative likelihood ratios of TVS ovarian immobility for diagnosis at surgery of immobility of ovaries with endometriomas in the left ovary only were 44.4%, 92.3%, 44.4%, 92.3%, 5.8, 0.6, in the right ovary only were 50.0%, 98.5%, 80.0%, 94.2%, 33.0, 0.5 and bilaterally were 74.4%, 68.6%, 72.5%, 70.6%, 2.4, 0.4, while those for diagnosis of immobility of normal ovaries were 25.0%, 87.9%, 8.3%, 96.4%, 2.1, 0.9 for left ovary only, 14.3%, 92.9%, 7.1%, 96.6%, 2.0, 0.9 for right ovary only and 35.7%, 97.2%, 50.0%, 95.0%, 12.6, 0.7 bilaterally, respectively (P < 0.05 except for normal left and right ovaries with P = 0.2 and 0.4, respectively). The sensitivity, specificity, PPV and NPV for performance of ovarian immobility in the prediction of DIE for all women were 58.3%, 74.1%, 60.6%, 72.2% and in the prediction of need for bowel surgery were 78.2%, 71.1%, 41.3%, 92.6%, respectively. CONCLUSIONS: There is a significant association between ovarian immobility and the presence of endometriomas. Ovarian immobility as a sonographic 'soft marker' of DIE performs better in the presence of endometriomas compared with in normal ovaries. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Laparoscopic sacrocolpopexy: how low does the mesh go?

OBJECTIVE: Laparoscopic sacrocolpopexy is becoming an increasingly popular surgical approach for repair of apical vaginal prolapse. The aim of this study was to document the postoperative anterior mesh position after laparoscopic sacrocolpopexy and to investigate the relationship between mesh location and anterior compartment support. METHODS: This was an external audit of patients who underwent laparoscopic sacrocolpopexy for apical prolapse ≥ Stage 2 or advanced prolapse ≥ Stage 3, between January 2005 and June 2012. All patients were assessed with a standardized interview, clinical assessment using the International Continence Society Pelvic Organ Prolapse quantification and four-dimensional transperineal ultrasound to evaluate pelvic organ support and mesh location. Mesh position was assessed with respect to the symphysis pubis whilst distal mesh mobility was assessed using the formula √[(XValsalva - Xrest )2 + (YValsalva - Yrest )2 ], where X is the horizontal distance and Y is the vertical distance between the mesh and the inferior symphyseal margin, measured at rest and on Valsalva. RESULTS: Ninety-seven women were assessed at a mean follow-up of 3.01 (range, 0.13-6.87) years after laparoscopic sacrocolpopexy, 88% (85/97) of whom considered themselves to be cured or improved, and none had required reoperation. On clinical examination, prolapse recurrence in the apical compartment was not diagnosed in any patient; however, 60 (62%) had recurrence in the anterior compartment and 43 (44%) in the posterior compartment. On ultrasound examination, mesh was visualized in the anterior compartment in 60 patients. Both mesh position and mobility on Valsalva were significantly associated with recurrent cystocele on clinical and on ultrasound assessment (all P < 0.01). For every mm that the mesh was located further from the bladder neck on Valsalva, the likelihood of cystocele recurrence increased by 6-7%. CONCLUSION: At an average follow-up of 3 years, laparoscopic sacrocolpopexy was highly effective for apical support; however, cystocele recurrence was common despite an emphasis on anterior mesh extension. Prolapse recurrence seemed to be related to mesh position and mobility, suggesting that the lower the mesh is from the bladder neck, the lower the likelihood of anterior compartment prolapse recurrence. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Application of ICD-PM to preterm-related neonatal deaths in South Africa and United Kingdom.

OBJECTIVE: We explore preterm-related neonatal deaths using the WHO application of the International Classification of Disease (ICD-10) to deaths during the perinatal period: ICD-PM as an informative case study, where ICD-PM can improve data use to guide clinical practice and programmatic decision-making. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa, and the UK. POPULATION: Perinatal death databases. METHODS: Descriptive analysis of neonatal deaths and maternal conditions present. MAIN OUTCOME MEASURES: Causes of preterm neonatal mortality and associated maternal conditions. RESULTS: We included 98 term and 173 preterm early neonatal deaths from South Africa, and 956 term and 3248 preterm neonatal deaths from the UK. In the South African data set, the main causes of death were respiratory/cardiovascular disorders (34.7%), low birthweight/prematurity (29.2%), and disorders of cerebral status (25.5%). Amongst preterm deaths, low birthweight/prematurity (43.9%) and respiratory/cardiovascular disorders (32.4%) were the leading causes. In the data set from the UK, the leading causes of death were low birthweight/prematurity (31.6%), congenital abnormalities (27.4%), and deaths of unspecified cause (26.1%). In the preterm deaths, the leading causes were low birthweight/prematurity (40.9%) and deaths of unspecified cause (29.6%). In South Africa, 61% of preterm deaths resulted from the maternal condition of preterm spontaneous labour. Among the preterm deaths in the data set from the UK, no maternal condition was present in 36%, followed by complications of placenta, cord, and membranes (23%), and other complications of labour and delivery (22%). CONCLUSIONS: ICD-PM can be used to appraise the maternal and newborn conditions contributing to preterm deaths, and can inform practice. TWEETABLE ABSTRACT: ICD-PM can be used to appraise maternal and newborn contributors to preterm deaths to improve quality of care.

Optimising the International Classification of Diseases to identify the maternal condition in the case of perinatal death.

OBJECTIVE: The WHO application of the tenth edition of the International Classification of Diseases (ICD-10) to deaths during the perinatal period (ICD Perinatal Mortality, ICD-PM) captures the essential characteristics of the mother-baby dyad that contribute to perinatal deaths. We compare the capture of maternal conditions in the existing ICD-PM with the maternal codes from the WHO application of ICD-10 to deaths during pregnancy, childbirth, and the puerperium (ICD Maternal Mortality, ICD-MM) to explore potential benefits in the quality of data received. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa and the UK. POPULATION: Perinatal death databases. METHODS: The maternal conditions were classified using the ICD-PM groupings for maternal condition in perinatal death, and then mapped to the ICD-MM groupings of maternal conditions. MAIN OUTCOME MEASURES: Main maternal conditions in perinatal deaths. RESULTS: We reviewed 9661 perinatal deaths. The largest group (4766 cases, 49.3%) in both classifications captures deaths where there was no contributing maternal condition. Each of the other ICD-PM groups map to between three and six ICD-MM groups. If the cases in each ICD-PM group are re-coded using ICD-MM, each group becomes multiple, more specific groups. For example, the 712 cases in group M4 in ICD-PM become 14 different and more specific main disease categories when the ICD-MM is applied instead. CONCLUSIONS: As we move towards ICD-11, the use of the more specific, applicable, and relevant codes outlined in ICD-MM for both maternal deaths and the maternal condition at the time of a perinatal death would be preferable, and would provide important additional information about perinatal deaths. TWEETABLE ABSTRACT: Improving the capture of maternal conditions in perinatal deaths provides important actionable information.

The WHO application of ICD-10 to deaths during the perinatal period (ICD-PM): results from pilot database testing in South Africa and United Kingdom.

OBJECTIVE: To apply the World Health Organization (WHO) Application of the International Classification of Diseases, tenth revision (ICD-10) to deaths during the perinatal period: ICD-Perinatal Mortality (ICD-PM) to existing perinatal death databases. DESIGN: Retrospective application of ICD-PM. SETTING: South Africa, UK. POPULATION: Perinatal death databases. METHODS: Deaths were grouped according to timing of death and then by the ICD-PM cause of death. The main maternal condition at the time of perinatal death was assigned to each case. MAIN OUTCOME MEASURES: Causes of perinatal mortality, associated maternal conditions. RESULTS: In South Africa 344/689 (50%) deaths occurred antepartum, 11% (n = 74) intrapartum and 39% (n = 271) in the early neonatal period. In the UK 4377/9067 (48.3%) deaths occurred antepartum, with 457 (5%) intrapartum and 4233 (46.7%) in the neonatal period. Antepartum deaths were due to unspecified causes (59%), chromosomal abnormalities (21%) or problems related to fetal growth (14%). Intrapartum deaths followed acute intrapartum events (69%); neonatal deaths followed consequences of low birthweight/ prematurity (31%), chromosomal abnormalities (26%), or unspecified causes in healthy mothers (25%). Mothers were often healthy; 53%, 38% and 45% in the antepartum, intrapartum and neonatal death groups, respectively. Where there was a maternal condition, it was most often maternal medical conditions, and complications of placenta, cord and membranes. CONCLUSIONS: The ICD-PM can be a globally applicable perinatal death classification system that emphasises the need for a focus on the mother-baby dyad as we move beyond 2015. TWEETABLE ABSTRACT: ICD-PM is a global system that classifies perinatal deaths and links them to maternal conditions.

Office gel sonovaginography for the prediction of posterior deep infiltrating endometriosis: a multicenter prospective observational study.

OBJECTIVE: To use office gel sonovaginography (SVG) to predict posterior deep infiltrating endometriosis (DIE) in women undergoing laparoscopy. METHODS: This was a multicenter prospective observational study carried out between January 2009 and February 2013. All women were of reproductive age, had a history of chronic pelvic pain and underwent office gel SVG assessment for the prediction of posterior compartment DIE prior to laparoscopic endometriosis surgery. Gel SVG findings were compared with laparoscopic findings to determine the diagnostic accuracy of office gel SVG for the prediction of posterior compartment DIE. RESULTS: In total, 189 women underwent preoperative gel SVG and laparoscopy for endometriosis. At laparoscopy, 57 (30%) women had posterior DIE and 43 (23%) had rectosigmoid/anterior rectal DIE. For the prediction of rectosigmoid/anterior rectal (i.e. bowel) DIE, gel SVG had an accuracy of 92%, sensitivity of 88%, specificity of 93%, positive predictive value (PPV) of 79%, negative predictive value (NPV) of 97%, positive likelihood ratio (LR+) of 12.9 and negative likelihood ratio (LR-) of 0.12 (P = 3.98E-25); for posterior vaginal wall and rectovaginal septum (RVS) DIE, respectively, the accuracy was 95% and 95%, sensitivity was 18% and 18%, specificity was 99% and 100%, PPV was 67% and 100%, NPV was 95% and 95%, LR+ was 32.4 and infinity and LR- was 0.82 and 0.82 (P = 0.009 and P = 0.003). CONCLUSIONS: Office gel SVG appears to be an effective outpatient imaging technique for the prediction of bowel DIE, with a higher accuracy for the prediction of rectosigmoid compared with anterior rectal DIE. Although the sensitivity for vaginal and RVS DIE was limited, gel SVG had a high specificity and NPV for all forms of posterior DIE, indicating that a negative gel SVG examination is highly suggestive of the absence of DIE at laparoscopy.

Prediction of pouch of Douglas obliteration in women with suspected endometriosis using a new real-time dynamic transvaginal ultrasound technique: the sliding sign.

OBJECTIVE: To evaluate preoperative real-time dynamic transvaginal sonography (TVS) in the prediction of pouch of Douglas (POD) obliteration in women undergoing laparoscopy for suspected endometriosis. METHODS: This was a multicenter prospective observational study undertaken from January 2009 to November 2011. All women with symptoms suggestive of endometriosis who were scheduled for laparoscopy underwent detailed preoperative TVS, in particular to ascertain whether the POD was obliterated. POD obliteration was assessed using a real-time TVS technique called the 'sliding sign'. Preoperative TVS sliding sign findings were then compared to gold standard laparoscopic POD findings. RESULTS: One hundred consecutive women with preoperative TVS and laparoscopic outcomes were included in the final analysis. Mean age was 32.8 years and mean age at diagnosis of endometriosis was 27.4 years. At laparoscopy, 84/100 (84%) were found to have some form of endometriosis (73% peritoneal endometriosis, 35% ovarian endometrioma(s), 33% deep infiltrating endometriosis). At laparoscopy, 30/100 (30%) had an obliterated POD and 19/30 (63.3%) of these women also had evidence of bowel endometriosis. The sonographic sliding sign technique had an accuracy of 93.0%, sensitivity of 83.3%, specificity of 97.1%, positive predictive value of 92.6%, negative predictive value of 93.2%, positive likelihood ratio of 29.2 and negative likelihood ratio of 0.17 in the prediction of POD obliteration (P = 1.8E-16). CONCLUSIONS: Preoperative real-time dynamic TVS evaluation using the sliding sign seems to establish with a high degree of certainty whether the POD is obliterated. Given the increased risk of deep infiltrating endometriosis in women with POD obliteration, the TVS sliding sign technique may also be useful in the identification of women who may be at a higher risk for bowel endometriosis.

The prevalence of maternal near miss: a systematic review.

BACKGROUND: Severe maternal morbidity or 'near miss' is a promising indicator to improve quality of obstetric care. OBJECTIVES: To systematically review all available studies on 'near miss'. SEARCH STRATEGY: Following a pre-defined protocol, our review covered articles between January 2004 and December 2010. We used a combination of the following terms: near miss morbidity, severe maternal morbidity, severe acute maternal morbidity, obstetric near-miss, maternal near miss, obstetric near miss, emergency hysterectomy, emergency obstetric hysterectomy, maternal complications, pregnancy complications, intensive care unit. SELECTION CRITERIA: Nearly 4000 articles were screened by title and abstract, and 153 articles were retrieved for full text evaluation. There were no language restrictions. DATA COLLECTION AND ANALYSIS: Data extraction was performed using an instrument that included sections on study characteristics, quality of reporting, prevalence/incidence and the definition and identification criteria. Univariate analysis and meta-analysis for sub-groups were performed. MAIN RESULTS: A total of 82 studies from 46 countries were included. Criteria for identification of cases varied widely. Prevalence rates varied between 0.6 and 14.98% for disease-specific criteria, between 0.04 and 4.54% for management-based criteria and between 0.14 and 0.92% for organ-based dysfunction based on Mantel criteria. The rates are higher in low-income and middle-income countries of Asia and Africa. Based on meta-analysis, the estimate of near miss was 0.42% (95% CI 0.40-0.44%) for the Mantel (organ dysfunction) criteria and 0.039% (95% CI 0.037-0.042%) for emergency hysterectomy. Our meta-regression results indicate that emergency hysterectomy rates have been increasing by about 8% per year. AUTHORS' CONCLUSIONS: There is growing interest in the application of the maternal near-miss concept as an adjunct to maternal mortality. However, in the literature published before 2011 there was still important variation in the criteria used to identify maternal near-miss cases. The World Health Organization recently published criteria based on markers of management and of clinical and organ dysfunction which would enable systematic data collection on near miss and development of summary estimates. Comparing the rates over time and across regions, it is clear that different approaches are needed to lower the rates of near miss and that interventions must be developed with the local context in mind.

Major trauma care at a regional trauma centre during the COVID-19 lockdown in England.

INTRODUCTION: The COVID-19 pandemic has changed the presentation of many medical and surgical conditions, including major trauma. We aimed to assess how lockdown changed the presentation, severity and management of major trauma patients at our level 1 trauma centre in England. METHODS: Data were collected retrospectively from the Trauma Audit and Research Network's database between 23 March and 28 April 2020 and compared with the same period in 2019. Collected data included patient demographics, and the mechanism, severity and management of injuries. RESULTS: We experienced a 56.4% reduction in major trauma admissions during the lockdown period when compared with 2019. In 2020, more patients arrived in haemodynamic shock (25.3% vs 12.2%, p=0.02); however, Glasgow Coma Scale and Injury Severity Score were unchanged. A higher proportion of incidents occurred at home (37.2% vs 53.5%, p=0.018), with no difference in trauma secondary to substance abuse or assault. During lockdown, patients had a significantly shorter hospital (17 vs 10 days, p=0.029) and critical care stay (2 vs 1 day, p=0.033). A higher proportion of major trauma patients were assessed by specialty trainees in the emergency department in 2020 (12.8% vs 53.1%, p=0.0001) with a lower proportion assessed by a consultant (69.8% vs 46.7%, p=0.001). CONCLUSIONS: The COVID-19 pandemic and lockdown drastically changed human behaviour, as reflected in the change in presentation of major trauma. Changes in the management of these patients reflect adaptive measures to manage the pressures generated by the worldwide pandemic.

Evaluation of 2 Novel Ratio-Based Metrics for Lumbar Spinal Stenosis.

BACKGROUND AND PURPOSE: Quantitative metrics of the dural sac such as the cross-sectional area are commonly used to evaluate central canal stenosis. The aim of this study was to analyze 2 new metrics to measure spinal stenosis on the basis of the ratio between the dural sac and disc cross-sectional areas (DDRCA) and the dural sac and disc anterior-posterior diameters (DDRDIA) and compare them with established quantitative metrics of the dural sac. MATERIALS AND METHODS: T2-weighted axial MR images (n = 260 patients) were retrospectively evaluated, graded for central canal stenosis as normal (no stenosis), mild, moderate, or severe from L1/L2 through L5/S1 with 1 grade per spinal level and annotated to measure the DDRCA and DDRDIA. Thresholds were obtained using a decision tree classifier on a subset of patients (n = 130) and evaluated on the remaining patients (n = 130) for accuracy and consistency across demographics, anatomic variation, and clinical outcomes. RESULTS: DDRCA and DDRDIA had areas under the receiver operating characteristic curve of 98.6 (97.4-99.3) and 98.0 (96.7-98.9) compared with dural sac cross-sectional area at 96.5 (95.0-97.7) for binary classification. DDRDIA and DDRCA had κ scores of 0.75 (0.71-0.79) and 0.80 (0.75-0.83) compared with dural sac cross-sectional area at 0.62 (0.57-0.66) for multigrade classification. No significant differences (P > .1) in the area under the receiver operating characteristic curve were observed for the DDRDIA across variations in the body mass index. The DDRDIA also had the highest area under the receiver operating characteristic curve among symptomatic patients (visual analog scale ≥ 7) or patients who underwent surgery. CONCLUSIONS: Ratio-based metrics (DDRDIA and DDRCA) are accurate and robust to anatomic and demographic variability compared with quantitative metrics of the dural sac and better correlated with symptomatology and surgical outcomes.

Low body mass index is associated with increased mortality in patients with pelvic and acetabular fractures.

AIMS: Fractures of the pelvis and acetabulum are often the consequence of high energy trauma in young individuals or fragility fractures in osteoporotic bone. They can be life-threatening or life changing injuries. No published data exists comparing body mass index (BMI) and mortality for this patient group. The aim of this study was to identify if low BMI (<18.5) was a predictor of morbidity and mortality for patients with these injuries. PATIENTS AND METHODS: Of the 1033 patients with pelvic or acetabular fractures referred to a single level 1 major trauma centre (MTC) over a 4.5-year period (August 2015 - January 2020); we retrospectively analysed data for all admitted patients. Data was collected on demographics, injury pattern, operative intervention and complications. Comparison was made between patients that were underweight (BMI<18.5) and patients that were not. Both in-hospital and post discharge complications were recorded including pulmonary embolus (PE), deep venous thrombosis (DVT), ileus, infection, loss of reduction and mortality at 6 months. RESULTS: 569 patients admitted to the MTC with a pelvic or acetabular fracture were included in our analysis. Underweight patients had a statistically significant increase in mortality both in-hospital (p = 0.019) and at 6 months post injury (p = 0.039) when compared to other BMI groups. No statistical significance was found between these BMI groups comparing morbidity: DVT (p = 0.712), PE (p = 0.736) nor ileus (p = 0.149). Covariate analysis showed that a low BMI was associated with triple the in-hospital mortality after correction for age and energy of injury (adjusted OR 3.028, 95% CI 1.059-8.659). CONCLUSION: This is the first published study that demonstrates a statistically significant increase in mortality in patients with pelvic or acetabular fractures who are underweight. Surgeons should carefully consider appropriate peri-operative optimisation for these patients. Further investigation into the effects of low BMI and response to trauma is required.

The global burden of trauma during the COVID-19 pandemic: A scoping review.

Purpose; The COVID-19 pandemic has necessitated profound adaptations in the delivery of healthcare to manage a rise in critically unwell patients. In an attempt to slow the spread of the virus nationwide lockdown restrictions were introduced. This review aims to scope the literature on the impact of the pandemic and subsequent lockdown on the presentation and management of trauma globally. Methods; A scoping review was conducted in accordance with PRISMA-ScR guidelines. A systematic search was carried out on the Medline, EMBASE and Cochrane databases to identify papers investigating presentation and management of trauma during the COVID-19 pandemic. All studies based on patients admitted with orthopaedic trauma during the COVID-19 pandemic were included. Exclusion criteria were opinion-based reports, reviews, studies that did not provide quantitative data and papers not in English. Results; 665 studies were screened, with 57 meeting the eligibility criteria. Studies reported on the footfall of trauma in the UK, Europe, Asia, USA, Australia and New Zealand. A total of 29,591 patients during the pandemic were considered. Mean age was 43.7 years (range <1-103); 54.8% were male. Reported reductions in trauma footfall ranged from 20.3% to 84.6%, with a higher proportion of trauma occurring secondary to interpersonal violence, deliberate self-harm and falls from a height. A decrease was seen in road traffic collisions, sports injuries and trauma occurring outdoors. There was no significant change in the proportion of patients managed operatively, and the number of trauma patients reported to be COVID-19 positive was low. Conclusion; Whilst the worldwide COVID-19 pandemic has caused a reduction in the number of trauma patients; the services managing trauma have continued to function despite infrastructural, personnel and pathway changes in health systems. The substantial effect of the COVID-19 pandemic on elective orthopaedics is well described, however the contents of this review evidence minimal change in the delivery of effective trauma care despite resource constraints during this global COVID-19 pandemic.

The L2/HNK-1 carbohydrate of neural cell adhesion molecules is involved in cell interactions.

We investigated whether the L2/HNK-1 carbohydrate epitope, expressed by two unusual glycolipids and several neural adhesion molecules, including L1, neural cell adhesion molecule, J1, and the myelin-associated glycoprotein, is involved in adhesion. Monoclonal L2 antibodies, the L2/HNK-1-reactive, sulfate-3-glucuronyl residue carrying glycolipids (L2 glycolipid) and a tetrasaccharide derived from the L2 glycolipid (L2 tetrasaccharide) were added to microexplant cultures of early postnatal mouse cerebellum, and cell migration and process extension were monitored. On the substrate poly-D-lysine, Fab fragments of L2 antibodies, L2 glycolipid, and L2 tetrasaccharide inhibited outgrowth of astrocytic processes and migration of cell bodies, but only L2 glycolipid and L2 tetrasaccharide reduced neurite outgrowth. On laminin, L2 antibodies, L2 glycolipid, and L2 tetrasaccharide inhibited outgrowth of astrocytic processes. Additionally, L2 glycolipid and L2 tetrasaccharide inhibited cell migration and neurite outgrowth. Several negatively charged glycolipids, lipids, and saccharides were tested for control and found to have no effect on outgrowth patterns, except for sulfatide and heparin, which modified outgrowth patterns in a similar fashion as L2 glycolipid and L2 tetrasaccharide. On astrocytes none of the tested compounds interfered with explant outgrowth. In short-term adhesion assays L2 glycolipid, sulfatide, and heparin inhibited adhesion of neural cells to laminin. L2 glycolipid and sulfatide interfered with neuron to astrocyte and astrocyte to astrocyte adhesion, but not with neuron-neuron adhesion. The most straightforward interpretation of these observations is that the L2/HNK-1 carbohydrate and the sulfated carbohydrates, sulfatide and heparin, act as ligands in cell adhesion.