Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in ...inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
Objectives
To update the 2012 ESGAR consensus guidelines on the acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for clinical staging and restaging of rectal cancer.
...Methods
Fourteen abdominal imaging experts from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) participated in a consensus meeting, organised according to an adaptation of the RAND-UCLA Appropriateness Method. Two independent (non-voting) Chairs facilitated the meeting. 246 items were scored (comprising 229 items from the previous 2012 consensus and 17 additional items) and classified as ‘appropriate’ or ‘inappropriate’ (defined by ≥ 80 % consensus) or uncertain (defined by < 80 % consensus).
Results
Consensus was reached for 226 (92 %) of items. From these recommendations regarding hardware, patient preparation, imaging sequences and acquisition, criteria for MR imaging evaluation and reporting structure were constructed. The main additions to the 2012 consensus include recommendations regarding use of diffusion-weighted imaging, criteria for nodal staging and a recommended structured report template.
Conclusions
These updated expert consensus recommendations should be used as clinical guidelines for primary staging and restaging of rectal cancer using MRI.
Key Points
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These guidelines present recommendations for staging and reporting of rectal cancer.
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The guidelines were constructed through consensus amongst 14 pelvic imaging experts.
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Consensus was reached by the experts for 92 % of the 246 items discussed.
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Practical guidelines for nodal staging are proposed.
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A structured reporting template is presented.
The association between pancreatic fat, obesity and metabolic disease is well-documented, and although a potentially exciting target for novel therapies, remains poorly understood. Non-invasive ...quantitative imaging-derived biomarkers can provide insights into pathophysiology and potentially provide robust trial endpoints for development of new treatments. In this review, we provide an overview of the pathophysiology of non-alcoholic fatty pancreas disease and associations with metabolic factors, obesity and diabetes. We then explore approaches to pancreatic fat quantification using ultrasound, CT and MRI, reviewing the strengths, limitations and current published evidence in the assessment of pancreatic fat. Finally, we explore the broader challenges of pancreatic fat quantification as we move toward translating these methods into the clinical setting.
A gap in emission inventories of urban volatile organic compound (VOC) sources, which contribute to regional ozone and aerosol burdens, has increased as transportation emissions in the United States ...and Europe have declined rapidly. A detailed mass balance demonstrates that the use of volatile chemical products (VCPs)-including pesticides, coatings, printing inks, adhesives, cleaning agents, and personal care products-now constitutes half of fossil fuel VOC emissions in industrialized cities. The high fraction of VCP emissions is consistent with observed urban outdoor and indoor air measurements. We show that human exposure to carbonaceous aerosols of fossil origin is transitioning away from transportation-related sources and toward VCPs. Existing U.S. regulations on VCPs emphasize mitigating ozone and air toxics, but they currently exempt many chemicals that lead to secondary organic aerosols.
Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current ...coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity.
We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites.
Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from - 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset.
RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.
Abstract Objectives To develop and validate a qualitative scoring system for enteric Crohn's disease activity using MR enterography (MRE). Methods MRE was performed in 16 patients (mean age 33, 8 ...male) undergoing small bowel resection. Mural thickness, T2 signal, contrast enhancement, and perimural oedema were scored qualitatively (0–3) at 44 locations. Transmural histopathological scoring of acute inflammation (AIS) was performed at all locations (score 0–13). MRI parameters best predicting AIS were derived using multivariate analysis. The MRI activity index was applied to 26 Crohn's patients (mean age 32, range 13–69 years, 15 male) and correlated to terminal ileal biopsy scores of acute inflammation (“eAIS” score 1–6). Receiver operator characteristic curves were calculated. Results Mural thickness (coefficient 1.34 (95% CI 0.36, 2.32), p = 0.007) and T2 signal (coefficient 0.90 (95% CI −0.24, 2.04) p = 0.06) best predicted AIS (AIS = 1.79 + 1.34*mural thickness + 0.94*mural T2 score R-squared 0.52). There was a significant correlation between the MRI index and eAIS (Kendall's tau = 0.40, 95% CI 0.11–0.64, p = 0.02). The model achieved a sensitivity of 0.81 (95% CI 0.54–0.96), specificity of 0.70 (0.35–0.93) and AUC 0.77 for predicting acute inflammation (eAIS ≥2). Conclusions A simple qualitative MRI Crohn's disease activity score appears predictive against a histopathological standard of reference.
Truncations of titin causing dilated cardiomyopathy Herman, Daniel S; Lam, Lien; Taylor, Matthew R G ...
New England journal of medicine/The New England journal of medicine,
02/2012, Volume:
366, Issue:
7
Journal Article
Peer reviewed
Open access
Dilated cardiomyopathy and hypertrophic cardiomyopathy arise from mutations in many genes. TTN, the gene encoding the sarcomere protein titin, has been insufficiently analyzed for cardiomyopathy ...mutations because of its enormous size.
We analyzed TTN in 312 subjects with dilated cardiomyopathy, 231 subjects with hypertrophic cardiomyopathy, and 249 controls by using next-generation or dideoxy sequencing. We evaluated deleterious variants for cosegregation in families and assessed clinical characteristics.
We identified 72 unique mutations (25 nonsense, 23 frameshift, 23 splicing, and 1 large tandem insertion) that altered full-length titin. Among subjects studied by means of next-generation sequencing, the frequency of TTN mutations was significantly higher among subjects with dilated cardiomyopathy (54 of 203 27%) than among subjects with hypertrophic cardiomyopathy (3 of 231 1%, P=3×10(-16)) or controls (7 of 249 3%, P=9×10(-14)). TTN mutations cosegregated with dilated cardiomyopathy in families (combined lod score, 11.1) with high (>95%) observed penetrance after the age of 40 years. Mutations associated with dilated cardiomyopathy were overrepresented in the titin A-band but were absent from the Z-disk and M-band regions of titin (P≤0.01 for all comparisons). Overall, the rates of cardiac outcomes were similar in subjects with and those without TTN mutations, but adverse events occurred earlier in male mutation carriers than in female carriers (P=4×10(-5)).
TTN truncating mutations are a common cause of dilated cardiomyopathy, occurring in approximately 25% of familial cases of idiopathic dilated cardiomyopathy and in 18% of sporadic cases. Incorporation of sequencing approaches that detect TTN truncations into genetic testing for dilated cardiomyopathy should substantially increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy. Defining the functional effects of TTN truncating mutations should improve our understanding of the pathophysiology of dilated cardiomyopathy. (Funded by the Howard Hughes Medical Institute and others.).
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