Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles.

Objectives: Positive autoantibody (AAB) titres are commonly encountered in autoimmune hepatitis (AIH) and in a proportion of drug-induced liver injury (DILI) patients. The underlying mechanism for selective AAB occurrence in DILI is unknown, but could be associated with variations in immune-associated genes. Hence, we aimed to analyse human leucocyte antigen (HLA) allele compositions in DILI with positive (+) and negative (-) AAB titres and in AIH patients. Methods: High-resolution genotyping of HLA class I (A, B, C) and II (DRB1, DQB1) loci was performed on 207 DILI and 50 idiopathic AIH patients and compared with 885 healthy Spanish controls. Results: Compared with controls, HLA-B*08:01 [44 vs. 9.7%, P=3.7E-13/corrected P-value (Pc)=1.0E-11], C*07:01 (46 vs. 24%, P=6.4E-04/Pc=0.012), DRB1*03:01 (58 vs. 21.5%, P=5.0E-09/Pc=1.0E-07) and DQB1*02:01 (56 vs. 22%, P=6.8E-08/Pc=9.0E-07) were significantly more frequent in AIH patients. The HLA-A*01:01 frequency was increased in the same population, but did not reach significance after Bonferroni's correction (34 vs. 19%, P=0.02/Pc=0.37). Fifty-eight of 207 DILI patients presented positive titres for at least one AAB (predominantly antinuclear antibody 76% and antismooth muscle antibody 28%). There was a tendency towards higher representation of DRB1*14:01 and DQB1*05:03 in DILI AAB+ compared with DILI AAB- (13.8 vs. 4.0%, P=0.02/Pc=0.5; 13.8 vs. 4.7%, P=0.04/Pc=0.5). Conclusion: The presence of HLA alleles B*08:01, C*07:01, DRB1*03:01, DQB1*02:01 and possibly A*01:01 enhances the risk of AIH (type 1) in Spanish patients. These alleles form part of the ancestral haplotype 8.1. HLA-DRB1*14:01 and DQB1*05:03 could potentially increase the risk of positive AAB (particularly antinuclear antibody) in Spanish DILI patients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Gastrointestinal Bleeding Following LVAD Placement from Top to Bottom

Abstract

Background

Left ventricular assist devices (LVADs) are an increasingly prevalent form of mechanical support for patients with end-stage heart failure. These devices can be implanted both as a bridge to transplant and as definitive/destination therapy. Gastrointestinal (GI) bleeding is one of the most common and recalcitrant long-term complications following LVAD implantation, with an incidence approaching 30 %.

Aims

This review will discuss what is known about the pathophysiology of GI bleeding in LVADs and the currently available options for medical and/or endoscopic management.

Results

The pathophysiology of bleeding is multifactorial, with hemodynamic alterations, acquired von Willebrand factor deficiency, and coagulopathy being most often implicated. The majority of bleeding events in this population result from angioectasias and gastroduodenal erosive disease. While these bleeding events are significant and often require transfusion therapy, they are rarely life threatening. Endoscopy remains the standard of care with upper endoscopy offering the highest diagnostic yield in these patients. However, the effectiveness of endoscopic hemostasis in this population is not well established. A small number of studies have evaluated medical therapy and alterations in LVAD settings as a means of preventing or treating bleeding with variable results.

Conclusions

In summary, GI bleeding with LVADs is a common occurrence and will continue to be as more LVADs are being performed for destination therapy.

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Double-Edged Sword: Esophageal and Colonic Crohn’s Disease

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A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations

Abstract

Background

Topical steroids prepared as oral viscous slurries have become common in the treatment of eosinophilic esophagitis. Esophageal mucosal contact time correlates with clinical and histologic improvement.

Aim

To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB.

Methods

A blinded randomized crossover trial investigating esophageal clearance of three OVB slurry preparations was done on healthy adults. Honey and xanthan gum OVB slurries were compared with standard sucralose OVB in 24 randomly assigned subjects. Each subject ingested the sucralose OVB and either the honey or xanthan gum OVB slurries. The esophageal clearance of each slurry was evaluated as an area under the curve (AUC) using 1 millicurie of technetium-99m-sulfur colloid (Tc99) co-administered in each OVB preparation using nuclear scintigraphy. A standardized taste survey was also administered.

Results

Xanthan gum had greater mucosal contact time compared to sucralose as measured by a higher AUC at 3 min (P = 0.002), while honey showed no significant difference in esophageal clearance relative to sucralose. Taste scores were significantly higher in the honey group, while scores for xanthan gum were no different from standard sucralose.

Conclusion

OVB slurries utilizing xanthan gum may be a superior alternative to a sucralose-based slurry due to its increased mucosal contact time and similar taste tolerance. Honey may be a suitable alternative as well, due to its similar contact time and favorable taste.

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Efficacy and Safety of Propofol-Mediated Sedation for Outpatient Endoscopic Retrograde Cholangiopancreatography (ERCP)

Abstract

Background and Aims

Propofol sedation for endoscopy may result in a rapid and unpredictable progression from deep sedation to general anesthesia, leading to potential complications. We investigated the incidence and predictors of sedation-related adverse events (SAEs) in nonintubated patients who underwent outpatient ERCP procedures with propofol sedation.

Methods

We conducted a retrospective study of patients who underwent propofol sedation for ERCP procedures. Patients were sedated using propofol in combination with low-dose opiates. Data collected included patient demographics, American Society of Anesthesiologists (ASAs) physical status, and procedure times. SAE includes hypoxia (pulse oximetry <90 %), hypotension (systolic blood pressure <90 mmHg), and conversation to endotracheal intubation. Factors associated with SAEs were examined by univariate analysis and multivariate regression analysis (MVA).

Results

A total of 3041 patients were evaluated. The median BMI was 25.2 kg/m², and the median ASA score was 3. The mean (±SD) duration of the procedures was 59 ± 23 min. Hypoxia requiring airway manipulation occurred in 28 % (n = 843) patients and hypotension requiring vasopressors in 0.4 % (n = 12). Forty-nine (1.6 %) patients required endotracheal intubation as a result of food in the stomach. Procedures underwent early termination in 8 (0.3 %) cases due to sedation-related hypotension (n = 5) and refractory laryngospasm (n = 3). Six patients were admitted after the ERCP for aspiration pneumonia as a result of sedation. Patients who developed SAE were older, had a higher mean BMI, and had longer mean procedure durations. On MVA, older age (p = 0.003), female sex (p = 0.001), BMI (p = 0.02), and ASA class ≥3 (p = 0.01) independently predicted SAEs.

Conclusions

Propofol can be used safely and effectively as a sedative agent for patients undergoing ERCPs when administered by trained professionals. Age, female sex, BMI, and ASA class ≥3 are independent predictors of SAEs.

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Correlation of Anti-mitochondrial Antibodies with Liver Histology and Outcomes

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Ultrasound-Guided Interscalene Block: Reevaluation of the "Stoplight" Sign and Clinical Implications.

Background and Objectives: The "stoplight" sign is a frequently described image during ultrasound-guided interscalene block, referring to 3 hypoechoic structures found between the anterior and middle scalene muscles. This study was designed to establish the ultrasound-anatomy correlation of this sign and to find any other anatomical features within the roots that could help with the interpretation of the ultrasound images obtained at the interscalene level. Methods: We performed 20 dissections of the brachial plexus in 10 embalmed human cadavers and systematically analyzed and measured the roots of C5 to C7 and then correlated these findings with ultrasonographic images on file. Results: We found that the C5 root is significantly smaller than either C6 or C7 (P

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