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Genome sequencing efforts have led to the discovery of tens of millions of protein missense variants found in the human population with the majority of these having no annotated role and some likely contributing to trait variation and disease. Sequence-based artificial intelligence approaches have become highly accurate at predicting variants that are detrimental to the function of proteins but they do not inform on mechanisms of disruption. Here we combined sequence and structure-based methods to perform proteome-wide prediction of deleterious variants with information on their impact on protein stability, protein-protein interactions and small-molecule binding pockets. AlphaFold2 structures were used to predict approximately 100,000 small-molecule binding pockets and stability changes for over 200 million variants. To inform on protein-protein interfaces we used AlphaFold2 to predict structures for nearly 500,000 protein complexes. We illustrate the value of mechanism-aware variant effect predictions to study the relation between protein stability and abundance and the structural properties of interfaces underlying trans protein quantitative trait loci (pQTLs). We characterised the distribution of mechanistic impacts of protein variants found in patients and experimentally studied example disease linked variants in FGFR1.
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Genomic variation can impact normal biological function in complex ways and so understanding variant effects requires a broad range of data to be coherently assimilated. Whilst the volume of human variant data and relevant annotations has increased, the corresponding increase in the breadth of participating fields, standards and versioning mean that moving between genomic, coding, protein and structure positions is increasingly complex. In turn this makes investigating variants in diverse formats and assimilating annotations from different resources challenging. ProtVar addresses these issues to facilitate the contextualization and interpretation of human missense variation with unparalleled flexibility and ease of accessibility for use by the broadest range of researchers. By precalculating all possible variants in the human proteome it offers near instantaneous mapping between all relevant data types. It also combines data and analyses from a plethora of resources to bring together genomic, protein sequence and function annotations as well as structural insights and predictions to better understand the likely effect of missense variation in humans. It is offered as an intuitive web server https://www.ebi.ac.uk/protvar where data can be explored and downloaded, and can be accessed programmatically via an API.
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Mutación Missense , Programas Informáticos , Humanos , Bases de Datos de Proteínas , Anotación de Secuencia Molecular , Proteoma/genética , Proteínas/genética , Proteínas/química , Internet , Genómica/métodosRESUMEN
PURPOSE: Single-sided portable NMR (pNMR) has previously been demonstrated to be suitable for quantification of mammographic density (MD) in excised breast tissue samples. Here we investigate the precision and accuracy of pNMR measurements of MD ex vivo as compared with the gold standards. METHODS: Forty-five breast-tissue explants from 9 prophylactic mastectomy patients were measured. The relative tissue water content was taken as the MD-equivalent quantity. In each sample, the water content was measured using some combination of three pNMR techniques (apparent T2, diffusion, and T1 measurements) and two gold-standard techniques (computed microtomography [µCT] and hematoxylin and eosin [H&E] histology). Pairwise correlation plots and Bland-Altman analysis were used to quantify the degree of agreement between pNMR techniques and the gold standards. RESULTS: Relative water content measured from both apparent T2 relaxation spectra, and diffusion decays exhibited strong correlation with the H&E and µCT results. Bland-Altman analysis yielded average bias values of -0.4, -2.6, 2.6, and 2.8 water percentage points (pp) and 95% confidence intervals of 13.1, 7.5, 11.2, and 11.8 pp for the H&E - T2, µCT - T2, H&E - diffusion, and µCT - diffusion comparison pairs, respectively. T1-based measurements were found to be less reliable, with the Bland-Altman confidence intervals of 27.7 and 33.0 pp when compared with H&E and µCT, respectively. CONCLUSION: Apparent T2-based and diffusion-based pNMR measurements enable quantification of MD in breast-tissue explants with the precision of approximately 10 pp and accuracy of approximately 3 pp or better, making pNMR a promising measurement modality for radiation-free quantification of MD.
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Densidad de la Mama , Espectroscopía de Resonancia Magnética , Humanos , Femenino , Espectroscopía de Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Persona de Mediana Edad , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Adulto , Mamografía/métodosRESUMEN
The European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) is one of the world's leading sources of public biomolecular data. Based at the Wellcome Genome Campus in Hinxton, UK, EMBL-EBI is one of six sites of the European Molecular Biology Laboratory (EMBL), Europe's only intergovernmental life sciences organisation. This overview summarises the latest developments in the services provided by EMBL-EBI data resources to scientific communities globally. These developments aim to ensure EMBL-EBI resources meet the current and future needs of these scientific communities, accelerating the impact of open biological data for all.
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Academias e Institutos , Biología Computacional , Biología Computacional/organización & administración , Biología Computacional/tendencias , Academias e Institutos/organización & administración , Academias e Institutos/tendencias , Bases de Datos de Ácidos Nucleicos , Europa (Continente)RESUMEN
Loss-of-function of DDX3X is a leading cause of neurodevelopmental disorders (NDD) in females. DDX3X is also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We perform saturation genome editing of DDX3X, testing in vitro the functional impact of 12,776 nucleotide variants. We identify 3432 functionally abnormal variants, in three distinct classes. We train a machine learning classifier to identify functionally abnormal variants of NDD-relevance. This classifier has at least 97% sensitivity and 99% specificity to detect variants pathogenic for NDD, substantially out-performing in silico predictors, and resolving up to 93% of variants of uncertain significance. Moreover, functionally-abnormal variants can account for almost all of the excess nonsynonymous DDX3X somatic mutations seen in DDX3X-driven cancers. Systematic maps of variant effects generated in experimentally tractable cell types have the potential to transform clinical interpretation of both germline and somatic disease-associated variation.
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Neoplasias , Trastornos del Neurodesarrollo , Femenino , Humanos , Edición Génica , Virulencia , Trastornos del Neurodesarrollo/genética , Neoplasias/genética , Células Germinativas , Mutación de Línea Germinal , ARN Helicasas DEAD-box/genéticaRESUMEN
Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic. We focused on 967 diagnostic-grade gene (DGG) variants for rare bleeding, thrombotic, and platelet disorders (BTPDs) observed in 12 367 UKB participants. By association analysis, for a subset of these variants, we estimated effect sizes for platelet count and volume, and odds ratios for bleeding and thrombosis. Variants causal of some autosomal recessive platelet disorders revealed phenotypic consequences in carriers. Loss-of-function variants in MPL, which cause chronic amegakaryocytic thrombocytopenia if biallelic, were unexpectedly associated with increased platelet counts in carriers. We also demonstrated that common variants identified by genome-wide association studies (GWAS) for platelet count or thrombosis risk may influence the penetrance of rare variants in BTPD DGGs on their associated hemostasis disorders. Network-propagation analysis applied to an interactome of 18 410 nodes and 571 917 edges showed that GWAS variants with large effect sizes are enriched in DGGs and their first-order interactors. Finally, we illustrate the modifying effect of polygenic scores for platelet count and thrombosis risk on disease severity in participants carrying rare variants in TUBB1 or PROC and PROS1, respectively. Our findings demonstrate the power of association analyses using large population datasets in improving pathogenicity classifications of rare variants.
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Estudio de Asociación del Genoma Completo , Trombosis , Humanos , Bancos de Muestras Biológicas , Hemostasis , Hemorragia/genética , Enfermedades RarasRESUMEN
BACKGROUND: It has previously been shown that CT scans performed for other indications can be used to identify patients with osteoporosis. This has not yet been tested in a British population. We sought to evaluate the use of vertebral CT attenuation measures for predicting osteoporosis in a British cohort, using dual-energy X-ray absorptiometry (DEXA) as a reference standard. METHODS: Patients who underwent abdominal CT in 2018 and concomitantly underwent DEXA within a six-month interval were retrospectively included. CT attenuation values in Hounsfield units (HU) were measured by placement of a region-of-interest at the central portion of the L1 vertebral body and then compared to their corresponding DEXA score. Receiver operating characteristic (ROC) curves were generated to evaluate the performance of a logistic regression model and to determine sensitivity and specificity thresholds. RESULTS: 536 patients (394 females, mean age 65.8) were included, of which 174 had DEXA-defined osteoporosis. L1 attenuation measures were significantly different (p < 0.01) between the three DEXA-defined groups of osteoporosis (118 HU), osteopenia (143 HU) and normal bone density (178 HU). The area under the ROC curve was 0.74 (95% CI 0.69-0.78). A threshold of 169 HU was 90% sensitive, and a threshold of 104 HU was 90% specific for diagnosing osteoporosis. CONCLUSIONS: Routine abdominal CT can be used to opportunistically screen for osteoporosis without additional cost or radiation exposure. The thresholds identified in this study are comparable with previous studies in other populations. We recommend radiologists engage with primary care and rheumatology providers to determine appropriate cut-off values for further investigation.
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Objectives: To evaluate the prevalence of sarcopenia in patients referred to a Multidisciplinary Chronic Pancreatitis (CP) Clinic at the University Hospitals of Leicester. Methods: All patients who had undergone CT scans were identified. Controls were identified from CT colonograms with no features of malignancy or pancreatic pathology. The psoas muscle index (PMI) was calculated using the formula: total psoas muscle cross-sectional area at the third lumbar vertebral level (cm2)/ the patient's height squared (m2). PMI cut-offs were <6.31cm2/m2 and <3.91cm2/m2 for males and females, respectively. Results: 58 CP CT scans were available for analysis along with 62 control scans. 71.9% of CP patients had a PMI below the cut-off for their gender, compared to 45.2% of the controls. The mean PMI (±SD) for male CP patients and male controls were 5.54cm2/m2 (±1.60) and 6.73 cm2/m2 (±1.54), (P=0.0023). The mean PMI (±SD) for female CP patients and female controls were 3.82 cm2/m2 (+/-1.46) and 4.98 cm2/m2 (+/-1.43), (P=0.0021). Conclusions: CP patients had a mean PMI below the cut-off value, suggesting that CP patients are largely sarcopenic. As malnutrition is a significant feature of CP, optimisation of nutrition may help to ameliorate sarcopenia in CP patients.
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The introduction of breast screening programs has led to the increased detection of occult breast lesions requiring diagnostic surgical biopsy or breast-conserving surgery for early-stage breast cancer. Excision of impalpable breast lesions can be challenging. Whilst a variety of techniques have now been described including the use of adjuncts such as hook wires, radioactive seeds, magnetic seeds or radiofrequency devices, many of these modalities are expensive and can be logistically problematic. The technique of surgeon-performed ultrasound-guided excision is a straightforward technique which is safe, cost-efficient and avoids a painful preoperative procedure for patients such as hook wire localisation. Whilst the use of intraoperative ultrasound-guided excision of breast lesions has been widely reported, the actual technique itself has been less well described.
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BACKGROUND: Research among military personnel and veterans indicates that subjective appraisal of warzone stressors explains the relation of combat exposure to posttraumatic stress disorder (PTSD), but not the relation of exposure to injury and death to PTSD. Studies have primarily been limited to conventional forces using aggregate measures of warzone stressor exposure. Threat appraisal may play a different role in the emergence of PTSD among military personnel for whom dangerous deployment experiences are more closely associated with exposure to injury and death, such as US Air Force Pararescuemen and Combat Rescue officers. MATERIALS AND METHODS: In a sample of 207 rescue personnel, correlations among various types of warzone stressor exposure, threat appraisal, and postdeployment PTSD symptoms were examined. RESULTS: The relative strongest correlates of threat appraisal were stressors related to injury, death, and human remains. Although exposure to these stressors was also correlated with PTSD symptom severity, partial correlations of stressor exposure and PTSD symptoms were no longer significant when adjusting for threat appraisal. CONCLUSION: Results support the contributing role of threat appraisal to PTSD among military personnel whose primary duties entail exposure to injury and death under hostile and dangerous conditions.
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Trastornos de Combate , Personal Militar , Trastornos por Estrés Postraumático , Veteranos , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos de Combate/complicaciones , Trastornos de Combate/diagnóstico , Guerra de Irak 2003-2011 , Campaña Afgana 2001-RESUMEN
AIM: We look at the effect of introducing the faecal immunochemical test (FIT) in the straight-to-test 2-week pathway for change in bowel habit (CIBH). METHOD: The FIT in primary care triages 2-week wait (2WW) colorectal referrals for patients aged 60 years and above for straight-to-test CT colonography (CTC). We compare the impact of the FIT on numbers of 2WW CTCs, in the year before and after FIT, in both colorectal cancer (CRC) detection and cost-effectiveness at both 4 µg Hb/g faeces and 10 µg Hb/g faeces. RESULTS: At a threshold of 4 µg Hb/g faeces, the positive predictive value of the FIT for diagnosis of CRC is 5.0% with a negative predictive value of 99.8% and a polyp detection rate of 25.5%. The introduction of the FIT resulted in a reduction in the number of CTCs performed through the CIBH pathway from a mean of 143.9 per month prior to the FIT to 66.8 CTCs per month once the FIT was well established. Given a FIT threshold of 10 µg Hb/g the number of CTCs would be predicted to fall by 70.4% to 42.6 CTCs per month resulting in higher CRC and polyp detection rate, and an estimated annual cost saving of £238 258 in our institution. CONCLUSION: The FIT use in primary care improves the yield of 2WW referrals for CIBH alone and reduces the burden and cost of investigations to exclude CRC. Improvements may be possible by increasing the cut-off employed, without adversely affecting the risk of missing a cancer.
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Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/diagnóstico , Sensibilidad y Especificidad , Hemoglobinas/análisis , Valor Predictivo de las Pruebas , Colonoscopía , Heces/química , Sangre Oculta , Detección Precoz del Cáncer/métodos , HábitosRESUMEN
Constrained Coding Regions (CCRs) in the human genome have been derived from DNA sequencing data of large cohorts of healthy control populations, available in the Genome Aggregation Database (gnomAD) [1]. They identify regions depleted of protein-changing variants and thus identify segments of the genome that have been constrained during human evolution. By mapping these DNA-defined regions from genomic coordinates onto the corresponding protein positions and combining this information with protein annotations, we have explored the distribution of CCRs and compared their co-occurrence with different protein functional features, previously annotated at the amino acid level in public databases. As expected, our results reveal that functional amino acids involved in interactions with DNA/RNA, protein-protein contacts and catalytic sites are the protein features most likely to be highly constrained for variation in the control population. More surprisingly, we also found that linear motifs, linear interacting peptides (LIPs), disorder-order transitions upon binding with other protein partners and liquid-liquid phase separating (LLPS) regions are also strongly associated with high constraint for variability. We also compared intra-species constraints in the human CCRs with inter-species conservation and functional residues to explore how such CCRs may contribute to the analysis of protein variants. As has been previously observed, CCRs are only weakly correlated with conservation, suggesting that intraspecies constraints complement interspecies conservation and can provide more information to interpret variant effects.
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Genoma Humano , Sistemas de Lectura Abierta , Proteínas , Humanos , Secuencia de Bases , Genoma Humano/genética , Genómica , Proteínas/genética , Mapeo CromosómicoRESUMEN
Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.
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Trastornos Relacionados con Anfetaminas/complicaciones , Granuloma/inducido químicamente , Metanfetamina/efectos adversos , Gastropatías/inducido químicamente , Endoscopía del Sistema Digestivo , Granuloma/diagnóstico , Granuloma/patología , Humanos , Masculino , Persona de Mediana Edad , Estómago/patología , Gastropatías/diagnóstico , Gastropatías/patologíaRESUMEN
INTRODUCTION: Antibiotic-resistant Gram-negative bacteria are of a growing concern globally, especially those producing enzymes conferring resistance. OXA-48-like carbapenemases hydrolyze most ß-lactam antibiotics, with typically low-level hydrolysis of carbapenems, but have limited effect on broad-spectrum cephalosporins. These are frequently co-expressed with extended spectrum ß-lactamases, especially CTX-M-15, which typically shows high level resistance to broad-spectrum cephalosporins, yet is carbapenem susceptible. The combined resistance profile makes the need for successful detection of these specific resistance determinants imperative for effective antibiotic therapy. OBJECTIVES: The objective of this study is to detect and identify OXA-48-like and CTX-M-15 enzymes using mass spectrometry, and to subsequently develop a method for detection of both enzyme types in combination with liquid chromatography. METHODS: Cells grown in either broth or on agar were harvested, lysed, and, in some cases buffer-exchanged. Lysates produced from bacterial cells were separated and analyzed via liquid chromatography with mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS). RESULTS: The intact proteins of OXA-48, OXA-181, and OXA-232 (collectively OXA-48-like herein) and CTX-M-15 were characterized and detected. Acceptance criteria based on sequence-informative fragments from each protein group were established as confirmatory markers for the presence of the protein(s). A total of 25 isolates were successfully tested for OXA-48 like (2), CTX-M-15 (3), or expression of both (7) enzymes. Thirteen isolates served as negative controls. CONCLUSIONS: Here we present a method for the direct and independent detection of both OXA-48-like carbapenemases and CTX-M-15 ß-lactamases using LC-MS/MS. The added sensitivity of MS/MS allows for simultaneous detection of at least two co-eluting, co-isolated and co-fragmented proteins from a single mass spectrum.
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Treatment of antibiotic-resistant infections is dependent on the detection of specific bacterial genes or proteins in clinical assays. Identification of methicillin-resistant Staphylococcus aureus (MRSA) is often accomplished through the detection of penicillin-binding protein 2a (PBP2a). With greater dependence on mass spectrometry (MS)-based bacterial identification, complementary efforts to detect resistance have been hindered by the complexity of those proteins responsible. Initial characterization of PBP2a indicates the presence of glycan modifications. To simplify detection, we demonstrate a proof-of-concept tandem MS approach involving the generation of N-terminal PBP2a peptide-like fragments and detection of unique product ions during top-down proteomic sample analyses. This approach was implemented for two PBP2a variants, PBP2amecA and PBP2amecC, and was accurate across a representative panel of MRSA strains with different genetic backgrounds. Additionally, PBP2amecA was successfully detected from clinical isolates using a five-minute liquid chromatographic separation and implementation of this MS detection strategy. Our results highlight the capability of direct MS-based resistance marker detection and potential advantages for implementing these approaches in clinical diagnostics.
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Proteínas Bacterianas/genética , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Proteínas de Unión a las Penicilinas/genética , Infecciones Estafilocócicas/microbiología , Espectrometría de Masas en Tándem/métodos , Secuencia de Aminoácidos , Proteínas Bacterianas/metabolismo , Técnicas de Tipificación Bacteriana , Humanos , Staphylococcus aureus Resistente a Meticilina/metabolismo , Proteínas de Unión a las Penicilinas/metabolismoRESUMEN
OBJECTIVE: The COVID-19 pandemic has led to cancellation and deferral of many cancer investigations, including CT colonography (CTC). In May 2020, BSGAR and SCoR issued guidelines outlining steps for conduct of CTC in the early recovery phase. We evaluated the implementation of these in four English hospital trusts. METHODS: Ethical permission was not required for this multicentre service evaluation. We identified patients undergoing CTC over a 2-month period from May to July 2020 at four Trusts. We recorded demographics, scan indications, colonic findings, and incidental lung base changes compatible with COVID-19. A subset of patients were contacted via telephone to document new symptoms 2 weeks following their scan. Staff were contacted to determine if any acquired COVID-19 during the period. RESULTS: 224 patients (118 male, 52.7%) were scanned during the period. In 55 patients (24.6%), CTC showed a ≥6 mm polyp. 33 of 224 (14.7%) scans showed incidental lung base changes felt unrelated to COVID-19, and only one patient had changes indeterminate for COVID-19; no classic COVID-19 pulmonary changes were found. Of 169 patients with telephone follow-up, none reported any new symptoms of COVID-19 (cough, fever, anosmia, ageusia) within 14 days of CTC. None of the 86 staff contacted developed COVID-19. CONCLUSION: We found no cases of patients or staff acquiring COVID-19 infection following CTC; and no evidence of significant asymptomatic COVID-19 patients attending for CTC appointments based on lung base changes. ADVANCES IN KNOWLEDGE: Our findings suggest that current practice is unlikely to contribute significantly to spread of SARS-nCOV2. Cancer and significant polyp detection rates were high, underlining the importance of maintaining service provision.
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COVID-19/epidemiología , Neoplasias del Colon/diagnóstico por imagen , Pólipos del Colon/diagnóstico por imagen , Colonografía Tomográfica Computarizada , Pandemias , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Asintomáticas , COVID-19/diagnóstico por imagen , COVID-19/transmisión , Femenino , Adhesión a Directriz , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
AIM: There is a requirement for an expansive and up to date review of the management of emergency colorectal conditions seen in adults. The primary objective is to provide detailed evidence-based guidelines for the target audience of general and colorectal surgeons who are responsible for an adult population and who practise in Great Britain and Ireland. METHODS: Surgeons who are elected members of the Association of Coloproctology of Great Britain and Ireland Emergency Surgery Subcommittee were invited to contribute various sections to the guidelines. They were directed to produce a pathology-based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. Each author was asked to provide a set of recommendations which were evidence-based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after two votes were included in the guidelines. RESULTS: All aspects of care (excluding abdominal trauma) for emergency colorectal conditions have been included along with 122 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence-based summary of the current surgical knowledge in the management of emergency colorectal conditions and should serve as practical text for clinicians managing colorectal conditions in the emergency setting.
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Cirugía Colorrectal , Procedimientos Quirúrgicos del Sistema Digestivo , Consenso , Servicio de Urgencia en Hospital , Humanos , Reino UnidoAsunto(s)
Neoplasias Cardíacas/secundario , Neoplasias Pulmonares/secundario , Neoplasias del Mediastino/cirugía , Pericardio , Teratoma/cirugía , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Masculino , Neoplasias del Mediastino/patología , Persona de Mediana Edad , Pericardio/diagnóstico por imagen , Pericardio/patología , Pericardio/cirugía , Teratoma/diagnóstico por imagen , Teratoma/patología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy in patients with esophageal carcinoma. Management of DGE varies widely and it is unclear how comorbidities influence the postoperative course. This study sought to determine factors that influence postoperative DGE. METHODS: This retrospective study evaluates patients who underwent esophagectomy with gastric pull-up between 2007 and 2019. The cohort was stratified in various ways to determine if postoperative care and outcomes differed, including patient demographics, comorbidities, intraoperative and postoperative procedures. RESULTS: During the study period, 149 patients underwent esophagectomy and 37 had diabetes. Overall incidence of DGE, as defined in this study, was 76.5%. Surgery type was significantly different between DGE and normal emptying cohorts (P = 0.005). Comparing diabetic and nondiabetic patients, there was no significant difference noted in DGE (P = 0.25). Additionally, there was no difference in presence of DGE for patients who underwent any intraoperative pyloric procedure compared to those who did not (P = 0.36). Of significance, all 16 patients with chronic obstructive pulmonary disease had a delay in gastric emptying (P = 0.01). CONCLUSIONS: A higher proportion of patients with DGE post-esophagectomy were identified compared to the literature. There is little consensus on a true definition of DGE, but we believe this definition identifies patients suffering in the immediate postoperative period and in follow-up. There is no evidence to support a different postoperative course for patients with diabetes, but the link between chronic obstructive pulmonary disease and DGE warrants further investigation.