Vedolizumab use after failure of TNF- antagonists in children and adolescents with inflammatory bowel disease

BACKGROUND: Vedolizumab is safe and effective in adult patients with Crohn's disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD. METHODS: Twelve patients (7 female; 7 CD; 5 UC), aged 8-17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits. RESULTS: In the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p=1,0), while median UC activity scores changed from 70 to 5 points (p<0,001). Substantial weight gain and increased albumin and haemoglobin levels were observed in both groups. CONCLUSION: These results demonstrate that vedolizumab can be an effective treatment for individual paediatric patients with IBD who are unresponsive, intolerant, or experience a loss of efficacy in other therapies. However, vedolizumab appears to be more effective in paediatric UC than in paediatric CD.(VLID)286504

R‑wave synchronised atrial pacing in pediatric patients with postoperative junctional ectopic tachycardia: the atrioventricular interval investigated by computational analysis and clinical evaluation

Background: R-wave synchronised atrial pacing is an effective temporary pacing therapy in infants with postoperative junctional ectopic tachycardia. In the technique currently used, adverse short or long intervals between atrial pacing and ventricular sensing (AP–VS) may be observed during routine clinical practice. Objectives: The aim of the study was to analyse outcomes of R-wave synchronised atrial pacing and the relationship between maximum tracking rates and AP–VS intervals. Methods: Calculated AP–VS intervals were compared with those predicted by experienced pediatric cardiologist. Results: A maximum tracking rate (MTR) set 10 bpm higher than the heart rate (HR) may result in undesirable short AP–VS intervals (minimum 83 ms). A MTR set 20 bpm above the HR is the hemodynamically better choice (minimum 96 ms). Effects of either setting on the AP–VS interval could not be predicted by experienced observers. In our newly proposed technique the AP–VS interval approaches 95 ms for HR > 210 bpm and 130 ms for HR < 130 bpm. The progression is linear and decreases strictly (− 0.4 ms/bpm) between the two extreme levels. Conclusions: Adjusting the AP–VS interval in the currently used technique is complex and may imply unfavorable pacemaker settings. A new pacemaker design is advisable to allow direct control of the AP–VS interval

A Low-Cost Simulation Model for R-Wave Synchronized Atrial Pacing in Pediatric Patients with Postoperative Junctional Ectopic Tachycardia.

Postoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing.A simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps.Four testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial.A realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique

European Journal of Clinical Investigation / The dilemma to diagnose Wilson disease by genetic testing alone

Background Wilson disease (WD) is an autosomal recessive disorder of hepatic copper excretion. About sixty per cent of patients present with liver disease. WD is considered a fatal disease if undiagnosed and/or untreated but recent data indicate that disease penetrance may not be 100%. Materials and Methods All patients underwent liver biopsy as part of the diagnostic workup. Genetic testing for ATP7B was performed by Sanger sequencing. Results We report on a large family with multiple affected siblings. The first patient (male, 31 years) underwent orthotopic liver transplantation (OLT) because of fulminant WD. He was homozygous for p.G710A. One asymptomatic brother (37 years) had the same mutation. He is doing well on chelation therapy. Fifteen years later, a seconddegree sibling (female, 16 years) presented with fulminant WD and underwent OLT. She was compound heterozygote (p.G710A/p.G710S). Further family screening revealed a third mutation (p.V536A) in a female (21 years) and male (16 years) compoundheterozygote sibling (p.G710A/p.V536A). In both, serum ceruloplasmin and 24hour urinary copper excretion were normal. Liver biopsy showed normal histology and a quantitative hepatic copper content within the normal range or only slightly elevated (19 and 75 g/g dry weight, respectively). No decoppering treatment was initiated so far. Conclusion Genetic testing alone is not always sufficient to diagnose WD in asymptomatic patients, and human mutation databases should be used with caution. Even patients carrying two diseasecausing mutations do not necessarily have demonstrable alteration of copper metabolism. Asymptomatic siblings diagnosed by genetic screening require further testing before initiating treatment.(VLID)510163

Inflammatory and coagulatory parameters linked to survival in critically ill children with sepsis

Abstract Background Sepsis is associated with a deflection of inflammatory and coagulative parameters, since some clotting factors are known to be involved in the host’s defense against infection and inflammation. These parameters could play a crucial role in the course of sepsis and be used as prognostic markers in critically ill children. Methods A total of 250 critically ill pediatric patients diagnosed with sepsis were retrospectively analyzed to identify routinely measured predictors for in-hospital mortality at the peak level of C-reactive protein. Those parameters entered multivariate logistic regression analysis as well as a decision tree for survival. Results Multivariate logistic regression analysis revealed fibrinogen, platelets and activated partial thromboplastin time (aPTT) at the peak level of C-reactive protein to be predictors for survival (p = 0.03, p = 0.01 and p = 0.02, respectively). An increase in fibrinogen and platelets is linked to survival, whereas an aPTT prolongation is associated with higher mortality; adjusted odds ratios (95% CI) for an increase of 100 mg/dl in fibrinogen are 1.35 (1.04–1.82) per 50 G/l platelets 1.94 (1.3–3.29) and 0.83 (0.69–0.96) for an aPTT prolongation of 10 s. Decision tree analysis shows that a fibrinogen level below 192 mg/dl (90.9% vs. 13% mortality) is most distinctive in non-survivors. Conclusions High levels of fibrinogen and platelets as well as a non-overshooting aPTT are associated with a higher survival rate in pediatric patients with diagnosed sepsis. In particular, hypofibrinogenemia is distinctive for a high mortality rate in septic critically ill children

Management of postoperative junctional ectopic tachycardia in pediatric patients: a survey of 30 centers in Germany, Austria, and Switzerland

Postoperative junctional ectopic tachycardia (JET) is a frequent complication after pediatric cardiac surgery. Current recommendations on how and when to treat JET are inconsistent. We evaluated the management strategies of postoperative JET in German-speaking countries. We sent an online survey to 30 centers of pediatric cardiology that perform surgery for congenital heart defects in Germany (24), Austria (4), and Switzerland (2). The survey asked 18 questions about how and in what treatment sequence postoperative JET was managed. All 30 centers completed the survey (100% return rate). There was general agreement that the management of JET is based on administration of antiarrhythmic drugs, body surface cooling, and temporary pacing. Many centers presented treatment algorithms based on published literature, all centers named amiodarone as the first drug of choice. Significant disagreement was found concerning the timing and sequential order of additional therapeutic measures and particularly about the dosing of amiodarone and the role of R-wave synchronized atrial pacing. CONCLUSION This survey reveals that from center to center, the treatment of postoperative JET may vary substantially. Future work should focus on those treatment modalities where a high rate of variation is found. Such studies may be of value to achieve commonly adopted treatment recommendations. What is known: • Treatment of postoperative junctional ectopic tachycardia is predominantly based on administration of antiarrhythmic drugs, therapeutic cooling, and temporary pacing. • Amiodarone is the antiarrhythmic drug of choice in this context. What is new: • Dosing and duration of administration of amiodarone differ relevantly from center to center. • The sequential order of drug administration, therapeutic cooling, and pacing is not consistent