Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram

The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up

The gut-brain axis in bipolar disorder and schizophrenia – a target for precision psychiatry?

BackgroundCurrently available pharmacotherapy for bipolar disorder (BD) and schizophrenia (SCZ) leave ample room for improvement. Evidence is accumulating that the immune system is more activated in patients with BD and SCZ, or at least in a subgroup of these patients. Abnormal immune responses have been reported in patients with BD, of varying disease stages and medication status3. Recent investigations have pointed to the gut-brain axis as a new venue for treatment, with increased inflammation stemming from leaky gut to further affect brain functioning in a significant subset of patients1,2. In a novel double blind randomized controlled trial, we will trans-dimensionally examine the effect of additional treatment with the probiotic product Ecologic Barrier (Winclove Probiotics, Amsterdam, the Netherlands) on psychiatric symptom improvement in 145 patients with BD or a psychotic disorder (GUTS RCT).Aim A state-of-the-art overview of available literature will be given on gut-brain functioning in BD and SCZ, including potential targets for future individualized treatment.MethodsLiterature reviewResultsTo date, multiple studies demonstrate food antigens to be increased in patients with BD and SCZ, compared to HC, which is related to an increased chance for rehospitalization4. Additionally, microbiological antigens were found to be increased in BD and SCZ patients as well, and an association with increased number of suicide attempts was described5. Also, significant microbiome disturbances have been described in BD and SCZ6. Finally, probiotic treatment was found to decrease rehospitalizations following mania in a recent RCT7 and may have beneficial effects on cognitive funcioning8.ConclusionProbiotics are promising candidates to improve BD patients’ symptomatology and functioning and there are rational methods to personalize its application with accessible and tolerable predictive biomarkers2. To further unravel the effects of probiotic treatment in these severe mental disorders and to allow future prediction of treatment, the GUTS RCT will be extended with measures of the intestinal microbiome, intestinal inflammation and intestinal permeability to predict the clinical effect of the probiotic product: calprotectin, microbiome in feces and lipopolysaccharides (LPS) binding protein (LBP) in serum.<br/

Additional file 1: of The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1

Table S1. Information_model. This table contains the information model of the 1000IBD phenotypes. (XLS 98 kb

Superior effectiveness of tofacitinib compared to vedolizumab in anti-TNF experienced ulcerative colitis patients: a nationwide Dutch Registry study

OBJECTIVE: Clinicians face difficulty in when and in what order to position biologics and JAK inhibitors in anti-TNF refractory ulcerative colitis (UC) patients. We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF exposed UC patients in our prospective nationwide Initiative on Crohn and Colitis (ICC) Registry. METHODS: UC patients who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment, were identified in the ICC Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (SCCAI≤2), biochemical remission (CRP ≤5 mg/L or fecal calprotectin ≤250 μg/g) and safety outcomes were compared after 52 weeks of treatment. Inverse propensity scores weighted comparison was used to adjust for confounding and selection bias. RESULTS: Overall, 83 vedolizumab and 65 tofacitinib treated patients were included. Propensity score weighted analysis showed that tofacitinib treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at week 12, 24 and 52 compared to vedolizumab treated patients (OR: 6.33, 95%CI:3.81-10.50, P<0.01, OR: 3.02, 95%CI: 1.89-4.84, P<0.01 and OR 1.86, 95%CI: 1.15-2.99, P=0.01 and OR: 3.27, 95%CI: 1.96-5.45, P<0.01, OR: 1.87, 95%CI: 1.14-3.07, P=0.01 and OR:1.81, 95%CI: 1.06-3.09, P=0.03, respectively. There was no difference in infection rate or severe adverse events. CONCLUSION: Tofacitinib was associated with superior effectiveness outcomes compared to vedolizumab in anti-TNF experienced UC patients along with comparable safety outcomes

Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study

Background & Aims: Clinicians face difficulty in when and in what order to position biologics and Janus kinase inhibitors in patients with anti-tumor necrosis factor-alpha (TNF) refractory ulcerative colitis (UC). We aimed to compare the effectiveness and safety of vedolizumab and tofacitinib in anti-TNF-exposed patients with UC in our prospective nationwide Initiative on Crohn and Colitis Registry. Methods: Patients with UC who failed anti-TNF treatment and initiated vedolizumab or tofacitinib treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands. We selected patients with both clinical as well as biochemical or endoscopic disease activity at initiation of therapy. Patients previously treated with vedolizumab or tofacitinib were excluded. Corticosteroid-free clinical remission (Simple Clinical Colitis Activity Index ≤2), biochemical remission (C-reactive protein ≤5 mg/L or fecal calprotectin ≤250 μg/g), and safety outcomes were compared after 52 weeks of treatment. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. Results: Overall, 83 vedolizumab- and 65 tofacitinib-treated patients were included. Propensity score-weighted analysis showed that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24, and 52 compared with vedolizumab-treated patients (odds ratio [OR], 6.33; 95% confidence interval [CI], 3.81–10.50; P < .01; OR, 3.02; 95% CI, 1.89–4.84; P < .01; and OR, 1.86; 95% CI, 1.15–2.99; P = .01; and OR, 3.27; 95% CI, 1.96–5.45; P < .01; OR, 1.87; 95% CI, 1.14–3.07; P = .01; and OR, 1.81; 95% CI, 1.06–3.09; P = .03, respectively). There was no difference in infection rate or severe adverse events. Conclusions: Tofacitinib was associated with superior effectiveness outcomes compared with vedolizumab in anti-TNF-experienced patients with UC along with comparable safety outcomes