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Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand’s activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500–24000] versus VV 28,800 IU [IQR 17,300–40,800.00]; < 0.001. Twenty-eight patients (72%) survived to hospital discharge; comprising 53% of VA patients and 77% of VV patients. Significant differences between the coagulation profiles of VA and VV patients exist, and anticoagulation strategies for patients of these modalities should be different. Further research into the development of tailored anticoagulation strategies that include the mode of ECMO support need to be completed.

The TEG 5000 and novel TEG 6s measure the viscoelasticity of whole blood during in vitro clot formation. The two devices measure similar coagulation variables but utilize distinctly different technologies. This study aimed to determine the correlation and agreement between the thrombelastographic parameters obtained by the two devices during liver transplant surgery. We obtained blood samples at six predefined intervals during the surgery of 10 consecutive patients. Two operators proficient in the use of the TEG 6s and TEG 5000 systems performed thrombelastographic measurements on each sample: non-citrated TEG 5000, citrated TEG 5000 and citrated TEG 6s. Agreement and correlation were assessed using Bland Altman plots and Lin's concordance correlation. There was considerable inter-device variability for the different parameters measured by the TEG 5000 and TEG 6s devices. Acceptable agreement was observed when results were within the normal reference ranges. However, with increasing coagulopathy, agreement was poor and results could not be considered interchangeable. Although each of the three tests appeared reliable for qualitative detection of abnormalities of clot formation during liver transplant surgery, we found their quantitative results were not interchangeable.

Patients with ulcerative colitis (UC) who are in clinical remission may still have underlying endoscopic inflammation, which is associated with inferior clinical outcomes. The goal of this study was to determine the prevalence of active endoscopic disease, and factors associated with it, in patients with UC who are in clinical remission.MethodsProspective observational study in a single center. Patients with UC in clinical remission (by Simple Clinical Colitis Activity Index) were enrolled prospectively at the time of surveillance colonoscopy. Disease phenotype, endoscopic activity (Mayo subscore), and histologic score (Geboes) were recorded, and blood was drawn for peripheral blood biomarkers.ResultsOverall, 149 patients in clinical remission were prospectively enrolled in this cohort; 81% had been in clinical remission for >6 months, and 86% were currently prescribed maintenance medications. At endoscopy, 45% of patients in clinical remission had any endoscopic inflammation (Mayo endoscopy subscore >0), and 13% had scores >1. In a multivariate model, variables independently associated with a Mayo endoscopic score >1 were remission for <6 months (P = 0.001), white blood count (P = 0.01), and C-reactive protein level (P = 0.009). A model combining these 3 variables had a sensitivity of 94% and a specificity of 73% for predicting moderate-to-severe endoscopic activity in patients in clinical remission (area under the curve, 0.86). In an unselected subgroup of patients who had peripheral blood mononuclear cell messenger RNA profiling, GATA3 messenger RNA levels were significantly higher in patients with endoscopic activity.ConclusionsDuration of clinical remission, white blood count, and C-reactive protein level can predict the probability of ongoing endoscopic activity, despite clinical remission in patients with UC. These parameters could be used to identify patients who require intensification of treatment to achieve mucosal healing.

Only a minority of patients commenced on anti-TNF agents achieve and maintain clinical remission, even with adequate serum drug levels and in the absence of anti-drug antibodies. The variable responsiveness of immune and other cell types to anti-TNF agents may partly explain this phenomenon. A means of identifying individuals with “responsive” mucosal immunology prior to selecting a biological agent could enhance remission rates, reduce costs and avoid safety concerns from ineffective use of anti-TNFs.MethodsWe developed an in vitro assay to test responsiveness of patients' biopsies to infliximab as determined by release of pro-inflammatory cytokines. Mucosal biopsies from 45 patients with IBD (24 males/21 females; 15% less than 16 years old, 42% between 17 and 40 years old; 29 with Crohn's disease/16 with ulcerative colitis) were cultured ex-vivo in the presence or absence of infliximab. Levels of 16 cytokines were measured in culture supernatants by multiplex ELISA. Patients were characterized as being “mucosal cytokine responders (MCRs)” if 3 or more cytokines were inhibited in the presence of infliximab. Cytokine responsiveness was correlated with clinical response to anti-TNF therapy in a subgroup of 28 patients with a follow-up of 6 to 54 weeks. Patients were categorized as clinical “non-responders” to anti-TNF treatment based on the following criteria (1) need for hospitalization or surgical intervention for IBD-related problems; (2) dose or frequency escalation of anti-TNF treatment or switching to another anti-TNF regimen; (3) switching to, or adding, another drug class.ResultsAmongst all mucosal samples cultured with infliximab, 44% of patients were categorized as mucosal cytokine responders (MCRs). In the cohort with clinical follow-up, 39% of patients were classified as clinical responders. Clinical responders had a greater number of cytokines inhibited in the assay compared to non-responders (6.0 ± 1.02 versus 1.29 ± 0.63 respectively; P = 0.0012 by Mann-Whitney test). IL-13, IL-17A, IL-5 and IL-7 were inhibited in 70% to 90% of clinical responders versus 10% in non-responders (P < 0.001). Clinical response rates to infliximab were 83.3% for MCRs (10 out of 12) versus 6.25% for cytokine non-responders (1 out of 16) (P = 0.0014). Based on a Receiver Operating Characteristic (ROC) analysis, the mucosal cytokine assay had 91% sensitivity and 88% specificity for predicting clinical response to anti-TNF (area under the curve 0.87).ConclusionsThese findings suggest that clinical responders to anti-TNF agents can be identified with high accuracy by testing mucosal biopsies in vitro in the presence of infliximab. If these results are replicated in a larger cohort, this mucosal cytokine assay could potentially be used to select patients for either starting or continuing anti-TNF therapy. Furthermore, in the future, it can be adapted to evaluate in parallel different candidate drugs and guide the delivery of personalized treatments in IBD.