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Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study.
The imaging and subsequent accurate diagnosis of paediatric brain tumours presents a radiological challenge, with magnetic resonance imaging playing a key role in providing tumour specific imaging information. Diffusion weighted and perfusion imaging are commonly used to aid the non-invasive diagnosis of children's brain tumours, but are usually evaluated by expert qualitative review. Quantitative studies are mainly single centre and single modality. The aim of this work was to combine multi-centre diffusion and perfusion imaging, with machine learning, to develop machine learning based classifiers to discriminate between three common paediatric tumour types. The results show that diffusion and perfusion weighted imaging of both the tumour and whole brain provide significant features which differ between tumour types, and that combining these features gives the optimal machine learning classifier with >80% predictive precision. This work represents a step forward to aid in the non-invasive diagnosis of paediatric brain tumours, using advanced clinical imaging
Emerging therapeutic targets for NASH: key innovations at the preclinical level.
: nonalcoholic steatohepatitis (NASH) is a globally emerging health problem, mainly caused by increasing trends in the prevalence of obesity and metabolic syndrome. Patients with NASH are mainly affected by cardiovascular risk and extrahepatic cancer, but a significant proportion of patients will develop advanced liver disease, eventually resulting in liver failure or hepatocellular carcinoma. Recent research has yielded a better understanding of the underlying mechanisms and potential targetability for drug development.: This review focuses on the role of fructose metabolism, lipogenesis (DNL), endoplasmic reticulum (ER) stress, NLRP3 inflammasome, bone morphogenetic protein (BMP) signaling and platelets in the pathophysiology of NASH. We discuss the suitability of these substrates for targeting liver disease as well as cardiovascular health in patients with NASH. A non-systematic literature search was performed on PubMed and ClinicalTrials.gov.: Targeting fructose metabolism, DNL, ER stress, NLRP3 inflammasome, BMP signaling and platelets are promising therapeutic strategies, warranting further preclinical and clinical investigation. The discussed approaches might not only benefit liver-related outcomes but improve cardiovascular disease as well. Amidst the euphoria of advances in drug development for NASH, parallel endeavors need to address the underlying causes of obesity and metabolic syndrome to prevent NASH
Prognosis review and time-to-event data meta-analysis of endovascular aneurysm repair outside versus within instructions for use of aortic endograft devices.
BACKGROUND
Our objective was to investigate whether patients undergoing standard endovascular aneurysm repair (EVAR) outside the instructions for use (IFU) have worse outcomes than patients treated within IFU.
METHODS
We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic bibliographic sources were searched up to January 2019 using a combination of controlled vocabulary (thesaurus) and free-text terms to identify studies comparing outcomes of EVAR in patients treated outside versus within IFU. Pooled estimates of dichotomous outcomes were calculated using odds ratio (OR) or risk difference (RD) and 95% confidence interval (CI). We conducted a time-to-event data meta-analysis using the inverse-variance method and reported the results as summary hazard ratio (HR) and associated 95% CI. Random-effects methods of meta-analysis were applied. We formed meta-regression models to explore heterogeneity as a result of changes in practice over time.
RESULTS
We identified 17 observational cohort studies published between 2011 and 2017, reporting a total of 4498 patients. The pooled prevalence of EVAR performed outside the IFU was 40% (95% CI, 33-48). Nonadherence to IFU was not associated with increased risk of perioperative mortality (RD, 0.01; 95% CI, -0.00 to 0.01; P = .23), aneurysm rupture (HR, 1.34; 95% CI, 0.30-5.93; P = .70), aneurysm-related mortality (HR, 0.88; 95% CI, 0.20-3.84; P = .86), technical failure (RD, 0.01; 95% CI, -0.03 to 0.05; P = .56), requirement for adjunctive procedures (OR, 1.48; 95% CI, 0.81-2.71; P = .20), type I endoleak (HR, 2.28; 95% CI, 0.58-8.91; P = .24), aneurysm sac expansion (HR, 0.86; 95% CI, 0.55-1.33; P = .49), or aneurysm-related reintervention (HR, 1.04; 95% CI, 0.81-1.34; P = .74). The overall mortality was significantly higher in patients treated outside the IFU (HR, 1.20; 95% CI, 1.02-1.42; P = .03). Meta-regression showed that the prevalence of EVAR performed outside the IFU has increased over time (P = .019).
CONCLUSIONS
Standard EVAR outside the IFU was not found to have worse aneurysm-related outcomes than treatment within the IFU. Standard EVAR outside the IFU could be considered in selected patients who are deemed high risk for complex open or endovascular surgery
Adult Presentation of X-Linked Retinoschisis: Patient and Physician Perspectives.
This commentary article is co-authored by an adult patient with X-linked retinoschisis and two ophthalmologists affiliated with the University Hospitals Birmingham NHS Foundation Trust. It describes the patient's experiences of sight loss and the diagnosis and management of X-linked retinoschisis. The treating ophthalmologists then draw upon these experiences and discuss the disease and associated sight loss in a wider context
Mapping the Steroid Response to Major Trauma From Injury to Recovery: A Prospective Cohort Study.
CONTEXT
Survival rates after severe injury are improving, but complication rates and outcomes are variable.
OBJECTIVE
This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery.
DESIGN
We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15).
MAIN OUTCOME MEASURES
We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models.
FINDINGS
We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis.
CONCLUSION
The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation
Case of small bowel perforation secondary to nivolumab and ipilimumab related tumour regression.
A 56-year-old man undergoing immunotherapy treatment for metastatic melanoma presented with sudden onset testicular pain radiating into his abdomen. On examination, the abdomen was generally tender with associated guarding. Imaging revealed a perforation of the small bowel at the site of a metastatic lesion. Histology revealed that this process was non-inflammatory in nature. A diagnosis of small bowel perforation secondary to immunotherapy driven rapid tumour regression was made. The patient was treated with a small bowel resection plus anastomosis and made a full recovery. This case highlights the rare potential side effect of immunotherapy in causing non-inflammatory bowel perforations secondary to rapid tumour regression
Deployed ophthalmic workload in support of US and NATO operations in Afghanistan.
PURPOSE
The extent and types of ophthalmic disease and non-battle injury (DNBI) seen by expeditionary ophthalmologists at deployed military medical treatment facilities have not previously been reported. We aim to characterise the extent and type of ophthalmic pathology including DNBI at a US military medical treatment facility in Afghanistan.
METHODS
We conducted a retrospective non-interventional cohort study of all patients seen by ophthalmologists at Craig Joint Theater Hospital at Bagram Airfield (BAF), Afghanistan, between 1 October 2018 and 31 August 2019.
RESULTS
There were 281 patients seen in 540 separate encounters, of which 146 patients seen were active duty military stationed at BAF with DNBI, of a population at risk of 6000 personnel. Diagnoses managed included open and closed globe injury, bacterial and herpetic keratitis and retinal detachment, with the most common being dry eye, corneal abrasion/foreign body, blepharitis, chalazion and uveitis. Thirteen patients (5%) required aeromedical evacuation out of theatre and 39 patients were aeromedically transferred within theatre for assessment. Expert consensus estimated that 89 patients (36%) would be likely to require aeromedical evacuation out of theatre without ophthalmic input.
CONCLUSIONS
The rate of ophthalmic DNBI among deployed US, UK and coalition forces at BAF was 2.65% per year, of whom 97% were returned to duty (95% of all patients). We estimate that evacuation and loss to unit would increase from 5% to 36% without an ophthalmologist present. The low number of within-theatre aeromedical transfers suggests that the local presence of an ophthalmologist at a patient's deployed medical treatment facility affects access to deployed ophthalmic care
Rhabdomyolysis: a case-based critical reflection on its causes and diagnosis.
Rhabdomyolysis is a rare and complex condition that involves injury of the skeletal muscle fibres, resulting in the release of substances such as creatine kinase and myoglobin. It is associated with acute kidney injury and mortality. This article describes the case of a 40-year-old man who presented to the emergency department after an overdose of tramadol hydrochloride. It uses critical reflection to explore traumatic and non-traumatic causes of rhabdomyolysis and reviews the literature relating to the diagnosis of rhabdomyolysis through laboratory and point-of-care testing. To ensure the timely identification of patients at risk of deterioration, emergency nurses need to be aware of the potential causes and the clinical signs and symptoms of rhabdomyolysis
The Outcomes of Emergency Admissions With Ulcerative Colitis Between 2007 and 2017 in England.
BACKGROUND AND AIMS
Patients with ulcerative colitis [UC] may present as emergencies and require rapid escalation of therapy. This study aimed to assess the mortality, colectomy, and readmission risks, during and following a first emergency admission with UC.
METHODS
Using Hospital Episode Statistics, subjects aged between 18 and 60 years, coded with a first emergency admission with UC, were identified between 2007 and 2017. Influences of demographic factors, comorbidity, anti-tumour necrosis factor [TNF] therapy, and provider UC activity on mortality and colectomy were examined.
RESULTS
A total of 10 051 subjects (46% female; median age 33 years [interquartile range [IQR] 25-44]) were identified. Mortality was 0.2% in hospital and 0.5% at 12 months and, following colectomy during acute admission, it was 1.4% in hospital and 2.1% at 12 months. Females had reduced risk of colectomy during admission: odds ratio [OR] 0.73 (95% confidence interval [CI] 0.62-0.85). Comparing the period 2007-2011 with 2012-2017, the rate of colectomy fell during acute admissions: OR 0.85 [0.72-0.99], p = 0.038 and at 12 months after admission: OR 0.73 [0.61-0.87]. Anti-TNF therapy increased 4-fold in acute UC admissions from 2007-2017. Those receiving anti-TNF therapy had a 70% increased risk of colectomy during index admission compared with those not receiving anti-TNF: OR 1.72 [1.29-2.31]. Increased time to colectomy during first admission was associated with female sex: hazard ratio [HR] 0.84 [0.72-0.98] and Asian ethnicity: HR 0.61 [0.44-0.85], whereas reduced time was associated with increased comorbidity, lower deprivation, and high provider volume of colectomies for UC: HR 1.59 [1.31-1.93].
CONCLUSIONS
Mortality following colectomy was 1.4% in hospital and 2.1% at 12 months, and no significant change over time was observed. Colectomy during emergency admission for UC was less common in females. Rates of anti-TNF therapy during emergency admission for UC have increased and overall colectomy rates have fallen.
PODCAST
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