Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Electroconvulsive therapy (ECT) is a fast-acting intervention for major depressive disorder. Previous studies indicated neurotrophic effects following ECT that might contribute to changes in white matter brain structure. We investigated the influence of ECT in a non-randomized prospective study focusing on white matter changes over time.

Twenty-nine severely depressed patients receiving ECT in addition to inpatient treatment, 69 severely depressed patients with inpatient treatment (NON-ECT) and 52 healthy controls (HC) took part in a non-randomized prospective study. Participants were scanned twice, approximately 6 weeks apart, using diffusion tensor imaging, applying tract-based spatial statistics. Additional correlational analyses were conducted in the ECT subsample to investigate the effects of seizure duration and therapeutic response.

Mean diffusivity (MD) increased after ECT in the right hemisphere, which was an ECT-group-specific effect. Seizure duration was associated with decreased fractional anisotropy (FA) following ECT. Longitudinal changes in ECT were not associated with therapy response. However, within the ECT group only, baseline FA was positively and MD negatively associated with post-ECT symptomatology.

Our data suggest that ECT changes white matter integrity, possibly reflecting increased permeability of the blood–brain barrier, resulting in disturbed communication of fibers. Further, baseline diffusion metrics were associated with therapy response. Coherent fiber structure could be a prerequisite for a generalized seizure and inhibitory brain signaling necessary to successfully inhibit increased seizure activity.

Dilated cardiomyopathy is a leading cause of cardiac death in children. Approximately 30% of children die or need cardiac transplantation in the first year after establishing the diagnosis. New strategies are needed to improve the outcome in this high-risk patient population.

We present our experience in 38 patients below the age of three years, who were diagnosed with dilated cardiomyopathy and who were treated at our institution between 2006 and 2012. The treatment strategy involved institution of β-blockers and angiotensin-converting enzyme inhibitors as soon as feasible. In selected cases, pulmonary artery banding or intracoronary autologous bone marrow-derived cell therapy was performed. The median age at presentation was six months (range 1–26 months). The median follow-up age was 16 months (range 2–80 months). Kaplan–Meier analysis of survival after dilated cardiomyopathy diagnosis revealed a one-year survival of 97% and a five-year survival of 86%. The rate of freedom from death or heart transplantation was 82% at one year and 69% at five years. Surviving patients who were free of transplantation, at the follow-up at 25 months (3–80 months), showed a significant improvement in left ventricular ejection fraction (from 19±11 to 46±16%) and left ventricular end-diastolic diameter (z-score from 4.6±2.4 to 1.4±1.6). In addition, the levels of B-type natriuretic peptide improved significantly (from 3330±3840 to 171±825 pg/ml).

Our data suggest that the clinical approach described here may result in a markedly improved medium-term outcome in young children with dilated cardiomyopathy. Further studies are required to evaluate whether these approaches reduce end-points such as transplantation or death.

In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports.

Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction.

Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.

Transcatheter stent placement carries the risk of cardiovascular aneurysm or rupture. Covered stent implantation reduces these risks. The recently marketed Advanta V12 large-diameter-covered stent is pre-mounted and requires 9 (8)-11 Fr delivery systems. The aim was to report on the early results of the treatment of various cardiovascular obstructions by the implantation of a new polytetrafluoroethylene-covered stent (V12).

Graft stents on balloons with a diameter (12, 14, 16 millimetres) sufficient to anchor the stent in various obstructions (congenital aortic coarctation, n = 5; obstruction after ascending aorta repair, n = 2; pulmonary arteries, n = 5; inferior caval vein, n = 1; atretic superior caval vein, n = 1; pulmonary vein obstruction, n = 1; and right ventricular outflow tract, n = 1) were implanted using the smallest available delivery system. Secondary dilation with larger-diameter balloons was performed when the residual pressure was gradient, the stent-vessel wall relationship or stent re-coiling due to different reasons needed a re-intervention by pure ballooning or second stent placement.

All 16 patients aged 5–46 years underwent V12 implantation. The variability of the treated lesions and the need for additional interventions were responsible for large ranges in fluoroscopy time between 7.3 to 48.2 minutes (median 17.3). Considering the additional procedures, the V12 stent achieved the desired result in all cases. There were no major complications. At short-term median follow-up of 2 months, all patients are alive and well with no evidence of stent failing.

These initial results show that the covered Advanta V12 large-diameter stent is safe and effective in the immediate treatment of various cardiovascular obstructions. Long-term follow-up is required.