Elevated liver enzymes in inflammatory bowel disease: the role and safety of infliximab

BACKGROUND: Abnormal liver enzymes are frequently encountered in inflammatory bowel disease (IBD) patients. Infliximab has been implicated in inducing drug-induced liver injury, autoimmune hepatitis or reactivation of hepatitis B virus. We aimed to clarify the role of infliximab in liver impairment in an IBD cohort. STUDY: A total of 305 patients with IBD, without evidence of chronic liver disease, were included in the study and retrospectively evaluated. Laboratory and clinical data were retrieved from a prospectively acquired database. In all, 176 consecutive patients treated with infliximab during the last 5 years were compared with a matched population of 129 patients who did not receive any antitumour necrosis factor treatment. RESULTS: Elevation of alanine transaminase (ALT) was frequent in the entire population (36.4%) and it was not significantly associated with the use of infliximab (P=0.284). Elevations more than 3 upper limit of normal were observed in 7.9% and these resolved spontaneously in 83%. The use of immunomodulators was the only factor that was significantly associated with liver enzyme abnormalities in multivariate analysis [odds ratio (OR) 2.666, 95% confidence interval (CI) 1.576-4.511, P<0.005]. Overall, 39% of patients on infliximab had elevated liver enzymes and this was associated with increased ALT before starting infliximab (OR 3.854, 95% CI 1.800-8.251, P=0.001) and with longer duration of infliximab treatment (OR 1.030, 95% CI 1.013-1.047, P=0.001). CONCLUSION: Elevated liver enzymes are frequently found in IBD patients and they usually resolve spontaneously. The use of immunomodulators was independently associated with increased ALT. Infliximab is relatively safe in terms of liver impairment and discontinuation of treatment is rarely required in the setting of modest elevations of ALT

Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma (HCC) in patients within Milan criteria.

Background: Increased preoperative inflammation scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and inflammation-based index (IBI) have been related to post-transplant HCC recurrence. We evaluated the association between inflammation-based scores (NLR, PLR, IBI) and post-LT HCC recurrence as well as tumour necrosis after transarterial embolisation. Methods: 150 consecutive patients that were transplanted for HCC within the Milan criteria between 1996-2010 were included; data regarding inflammatory markers, patient and tumour characteristics were analyzed. Results: NLR, PLR and IBI were not significantly associated with post-LT HCC recurrence or worse overall survival. Increased NLR and PLR were associated with complete tumour necrosis in the subset of patients that received preoperative transarterial embolization (P<0.05). Cox regression analysis revealed that absence of neo-adjuvant transarterial therapy (OR=4.33, 95%CI 1.28-14.64; P=0.02) and no fulfilment of the Milan criteria in the explanted liver (OR=3.34, 95%CI 1.08-10.35; P=0.04) were independently associated with post-LT HCC recurrence. Conclusion: Inflammation-based scores did not predict HCC recurrence post-LT in our group of patients. NLR and PLR were associated with better response to TAE, as this was recorded histologically in the explanted liver. Histological fulfilment of the Milan criteria and absence of neo-adjuvant transarterial treatment were significantly associated with post-LT HCC recurrence. Liver Transpl , 2014. © 2014 AASLD

Academic requirements for Certificate of Completion of Training in surgical training: Consensus recommendations from the Association of Surgeons in Training/National Research Collaborative Consensus Group.

BACKGROUND: Surgical trainees are expected to demonstrate academic achievement in order to obtain their certificate of completion of training (CCT). These standards are set by the Joint Committee on Surgical Training (JCST) and specialty advisory committees (SAC). The standards are not equivalent across all surgical specialties and recognise different achievements as evidence. They do not recognise changes in models of research and focus on outcomes rather than process. The Association of Surgeons in Training (ASiT) and National Research Collaborative (NRC) set out to develop progressive, consistent and flexible evidence set for academic requirements at CCT. METHODS: A modified-Delphi approach was used. An expert group consisting of representatives from the ASiT and the NRC undertook iterative review of a document proposing changes to requirements. This was circulated amongst wider stakeholders. After ten iterations, an open meeting was held to discuss these proposals. Voting on statements was performed using a 5-point Likert Scale. Each statement was voted on twice, with ≥80% of votes in agreement meaning the statement was approved. The results of this vote were used to propose core and optional academic requirements for CCT. RESULTS: Online discussion concluded after ten rounds. At the consensus meeting, statements were voted on by 25 delegates from across surgical specialties and training-grades. The group strongly favoured acquisition of 'Good Clinical Practice' training and research methodology training as CCT requirements. The group agreed that higher degrees, publications in any author position (including collaborative authorship), recruiting patients to a study or multicentre audit and presentation at a national or international meeting could be used as evidence for the purpose of CCT. The group agreed on two essential 'core' requirements (GCP and methodology training) and two of a menu of four 'additional' requirements (publication with any authorship position, presentation, recruitment of patients to a multicentre study and completion of a higher degree), which should be completed in order to attain CCT. CONCLUSION: This approach has engaged stakeholders to produce a progressive set of academic requirements for CCT, which are applicable across surgical specialties. Flexibility in requirements whilst retaining a high standard of evidence is desirable

Low bone mass in microscopic colitis

<p>Abstract</p> <p>Background</p> <p>Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis.</p> <p>Aims</p> <p>The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis.</p> <p>Methods</p> <p>Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays.</p> <p>Results</p> <p>Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm²; p < 0.01). Bone mineral density at the non-dominant radius was decreased in microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm²; p < 0.05) but unaffected in Crohn's disease patients (0.672 ± 0.056 g/cm²). Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p < 0.05). A negative correlation between beta-crosslaps concentration and the femoral and radius t-scores was evident in microscopic colitis patients.</p> <p>Conclusions</p> <p>Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.</p

Altered sensory-weighting mechanisms is observed in adolescents with idiopathic scoliosis

BACKGROUND: Scoliosis is the most common type of spinal deformity. In North American children, adolescent idiopathic scoliosis (AIS) makes up about 90% of all cases of scoliosis. While its prevalence is about 2% to 3% in children aged between 10 to 16 years, girls are more at risk than boys for severe progression with a ratio of 3.6 to 1. The aim of the present study was to test the hypothesis that idiopathic scoliosis interferes with the mechanisms responsible for sensory-reweighting during balance control. METHODS: Eight scoliosis patients (seven female and one male; mean age: 16.4 years) and nine healthy adolescents (average age 16.5 years) participated in the experiment. Visual and ankle proprioceptive information was perturbed (eyes closed and/or tendon vibration) suddenly and then returned to normal (eyes open and/or no tendon vibration). An AMTI force platform was used to compute centre of pressure root mean squared velocity and sway density curve. RESULTS: For the control condition (eyes open and no tendon vibration), adolescent idiopathic scoliosis patients had a greater centre of pressure root mean squared velocity (variability) than control participants. Reintegration of ankle proprioception, when vision was either available or removed, led to an increased centre of pressure velocity variability for the adolescent idiopathic scoliosis patients whereas the control participants reduced their centre of pressure velocity variability. Moreover, in the absence of vision, adolescent idiopathic scoliosis exhibited an increased centre of pressure velocity variability when ankle proprioception was returned to normal (i.e. tendon vibration stopped). The analysis of the sway density plot suggests that adolescent idiopathic scoliosis patients, during sensory reintegration, do not scale appropriately their balance control commands. CONCLUSION: Altogether, the present results demonstrate that idiopathic scoliosis adolescents have difficulty in reweighting sensory inputs following a brief period of sensory deprivation

Identification and Characterization of an Unusual Class I Myosin Involved in Vesicle Traffic in Trypanosoma brucei

Myosins are a multimember family of motor proteins with diverse functions in eukaryotic cells. African trypanosomes possess only two candidate myosins and thus represent a useful system for functional analysis of these motors. One of these candidates is an unusual class I myosin (TbMyo1) that is expressed at similar levels but organized differently during the life cycle of Trypanosoma brucei. This myosin localizes to the polarized endocytic pathway in bloodstream forms of the parasite. This organization is actin dependent. Knock down of TbMyo1 results in a significant reduction in endocytic activity, a cessation in cell division and eventually cell death. A striking morphological feature in these cells is an enlargement of the flagellar pocket, which is consistent with an imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed throughout procyclic forms of the tsetse vector and a loss of ∼90% of the protein has no obvious effects on growth or morphology. These results reveal a life cycle stage specific requirement for this myosin in essential endocytic traffic and represent the first description of the involvement of a motor protein in vesicle traffic in these parasites

Academic requirements for certificate of completion of training in surgical training: consensus recommendations from the Association of Surgeons in Training/National Research Collaborative Consensus Group

Background Surgical trainees are expected to demonstrate academic achievement in order to obtain their certificate of completion of training (CCT). These standards are set by the Joint Committee on Surgical Training (JCST) and specialty advisory committees (SAC). The standards are not equivalent across all surgical specialties and recognise different achievements as evidence. They do not recognise changes in models of research and focus on outcomes rather than process. The Association of Surgeons in Training (ASiT) and National Research Collaborative (NRC) set out to develop progressive, consistent and flexible evidence set for academic requirements at CCT. Methods A modified-Delphi approach was used. An expert group consisting of representatives from the ASiT and the NRC undertook iterative review of a document proposing changes to requirements. This was circulated amongst wider stakeholders. After ten iterations, an open meeting was held to discuss these proposals. Voting on statements was performed using a 5-point Likert Scale. Each statement was voted on twice, with ≥80% of votes in agreement meaning the statement was approved. The results of this vote were used to propose core and optional academic requirements for CCT. Results Online discussion concluded after ten rounds. At the consensus meeting, statements were voted on by 25 delegates from across surgical specialties and training-grades. The group strongly favoured acquisition of ‘Good Clinical Practice’ training and research methodology training as CCT requirements. The group agreed that higher degrees, publications in any author position (including collaborative authorship), recruiting patients to a study or multicentre audit and presentation at a national or international meeting could be used as evidence for the purpose of CCT. The group agreed on two essential ‘core’ requirements (GCP and methodology training) and two of a menu of four ‘additional’ requirements (publication with any authorship position, presentation, recruitment of patients to a multicentre study and completion of a higher degree), which should be completed in order to attain CCT. Conclusion This approach has engaged stakeholders to produce a progressive set of academic requirements for CCT, which are applicable across surgical specialties. Flexibility in requirements whilst retaining a high standard of evidence is desirable

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts