Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians

PURPOSE: The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians. METHODS: 77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895 (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF), and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays. Chi square analysis was used to test for association of allele and genotype with overall AIH, and with severe fibrosis and ALT levels at 6 months. RESULTS: Significant risk of AIH was conferred by the minor alleles of rs2187668 (OR = 2.45, 95% CI 1.65-3.61, p < 0.0001), rs3749971 (OR = 1.89, 95% CI 1.21-2.94, p = 0.004) and rs1800629 (OR = 2.06, 95% CI 1.41-3.01, p = 0.0001). Multivariate analysis showed that rs2187668 was independently associated with type 1 AIH susceptibility (OR = 2.40, 95% CI 1.46-3.93, p = 0.001). The C allele of FAS SNP rs1800682 was associated with increased risk of severe fibrosis at diagnosis (OR = 2.03, 95% CI 1.05-3.93, p = 0.035) and with incomplete normalization of ALT levels at 6 months post-diagnosis (OR = 3.94, 95% CI 1.62-9.54, p = 0.0015). CONCLUSIONS: This is the first population-based study to investigate genetic risk loci for type 1 AIH in New Zealand Caucasians. We report significant independent association of HLA-DRB1*03:01 with overall susceptibility to type 1 AIH, as well as FAS with a more aggressive disease phenotype

Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study

Objective: To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. Design: International multicentre prospective study. Setting: Six large hospitals in Europe, North America, Asia, and Oceania. Participants: 3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding. Main outcome measures: Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined. Results: The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P&lt;0.001). A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P&lt;0.001). A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P&lt;0.001). Score thresholds of ≥4 for PNED, ≥2 for AIMS65, ≥4 for admission Rockall, and ≥5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length of stay. Conclusions: The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of ≤1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited. Trial registration: Current Controlled Trials ISRCTN16235737

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Relationship of time to presentation after onset of upper GI bleeding with patient characteristics and outcomes: a prospective study

Background and Aims: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes. Methods: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours. Results: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus &gt;6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus &gt;6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, −15%; 95% CI, −19% to −12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2). Conclusions: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation

MAP(ASH): A new scoring system for the prediction of intervention and mortality in upper gastrointestinal bleeding

Risk stratification for upper gastrointestinal bleeding (UGIB) is recommended. However, scoring system accuracy is suboptimal, and score calculation can be complex. Our aim was to develop a new score, the MAP(ASH) score, with information available in the emergency room and to validate it. The score was built from a prospective database of patients with UGIB and validated in an international database of 3012 patients from six hospitals. Outcomes were 30-day mortality, endoscopic intervention, any intervention (red blood transfusion, endoscopic treatment, interventional radiology, surgery, or death), and rebleeding. Accuracy to predict outcomes was assessed by the area under the receiver operating characteristic curve (AUROC). Five hundred forty-seven patients were included in the development cohort. Impaired mental status, albumin  100, American Society of Anesthesiologists score > 2, systolic blood pressure  2, systolic blood pressure  MAP(ASH) is a simple pre-endoscopy risk score to predict intervention after UGIB, with fair discrimination at predicting mortality. Because of its applicability, it could be an option in clinical practice

MAP(ASH): A new scoring system for the prediction of intervention and mortality in upper gastrointestinal bleeding.

Risk stratification for upper gastrointestinal bleeding (UGIB) is recommended. However, scoring system accuracy is suboptimal, and score calculation can be complex. Our aim was to develop a new score, the MAP(ASH) score, with information available in the emergency room and to validate it. The score was built from a prospective database of patients with UGIB and validated in an international database of 3012 patients from six hospitals. Outcomes were 30-day mortality, endoscopic intervention, any intervention (red blood transfusion, endoscopic treatment, interventional radiology, surgery, or death), and rebleeding. Accuracy to predict outcomes was assessed by the area under the receiver operating characteristic curve (AUROC). Five hundred forty-seven patients were included in the development cohort. Impaired mental status, albumin  100, American Society of Anesthesiologists score > 2, systolic blood pressure  2, systolic blood pressure  MAP(ASH) is a simple pre-endoscopy risk score to predict intervention after UGIB, with fair discrimination at predicting mortality. Because of its applicability, it could be an option in clinical practice

Previous use of antithrombotic agents reduces mortality and length of hospital stay in patients with high-risk upper gastrointestinal bleeding

Background &amp; Aims: Anti-thrombotic agents are risk factors for upper gastrointestinal bleeding (UGIB). However, few studies have evaluated their effects on patient outcomes. We assessed the effects of anti-thrombotic agents on outcomes of patients with high-risk UGIB. Methods: We performed a prospective study of 619 patients with acute UGIB (defined by hematemesis, coffee-ground vomit or melena) who required intervention and underwent endoscopy at 8 centers in North America, Asia, and Europe, from March 2014 through March 2015. We collected data recorded on use of anti-thrombotic agents, clinical features, and laboratory test results to calculate AIMS65, Glasgow-Blatchford Score, and full Rockall scores. We also collected and analyzed data on co-morbidities, endoscopic findings, blood transfusion, interventional radiology results, surgeries, length of hospital stay, rebleeding, and mortality. Results: Of the 619 patients who required endoscopic therapy, data on use of anti-thrombotic agents was available for 568; 253 of these patients (44%) used anti-thrombotic agents. Compared to patients not taking anti-thrombotic agents, patients treated with anti-thrombotics were older (P &lt; .001), had a higher mean American Society of Anesthesiologists classification score (P &lt; .0001), had a higher mean Rockall score (P &lt; .0001), a higher mean AIMS65 score (P &lt; .0001), and more frequently bled from ulcers (P &lt; .001). There were no differences between groups in sex, systolic blood pressure, level of hemoglobin at hospital admission, frequency of malignancies, Glasgow-Blatchford Score, need for surgery or interventional radiology, number of rebleeding events, or requirement for transfusion. All-cause mortality was lower in patients who took anti-thrombotic drugs (11 deaths, 4%) than in patients who did not (37 deaths, 12%) (P = .002); this was due to lower bleeding-related mortality in patients taking anti-thrombotic drugs (3 deaths, 1%) than in patients who were not (19 deaths, 6%) (P = .003). Patients taking anti-thrombotic drugs had mean hospital stays of 6.9 days (95% CI, 2–23 days) compared to 7.9 days for non-users of anti-thrombotic agents (95% CI, 2–26 days) (P = .04). Conclusions: Despite being older, with higher American Society of Anesthesiologists classification, AIMS65, and Rockall scores, patients who have UGIB that requires endoscopic therapy and take anti-thrombotic drugs have lower mortality due to GI bleeding and shorter hospital stays, with similar rates of rebleeding, surgery, and transfusions, compared with those not taking anti-thrombotic drugs