Schwann cell hamartoma: case report

<p>Abstract</p> <p>Background</p> <p>Colorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening.</p> <p>Case presentation</p> <p>We report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract.</p> <p>Conclusion</p> <p>As recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma.</p

Fibroblast growth factor receptor-1 phosphorylation requirement for cardiomyocyte differentiation in murine embryonic stem cells.

Fibroblast growth factor receptor-1 (Fgfr1) gene knockout impairs cardiac and haematopoietic development in murine embryonic stem cells (mESC). In FGFR1, tyrosine residues Y653 and Y654 are responsible for its tyrosine kinase (TK) activity whereas phosphorylated Y463 and Y766 represent docking sites for intracellular substrates. Aim of this study was the characterization of FGFR1 signalling requirements necessary for cardiomyocyte differentiation in mESC. To this purpose, fgfr1(-/-) mESC were infected with lentiviral vectors harbouring human wild-type hFGFR1 or the Y653/654F, Y463F and Y766F hFGFR1 mutants. The resulting embryonic stem (ES) cell lines were differentiated as embryoid bodies (EBs) and beating foci formation was evaluated. In order to appraise the presence of cells belonging to cardiovascular and haematopoietic lineages, specific markers were analysed by quantitative PCR, whole mount in situ hybridization and immunofluorescence. Transduction with TK(+) hFGFR1 or the TK(+) Y766F-hFGFR1 mutant rescued cardiomyocyte beating foci formation in fgfr1(-/-) EBs whereas the TK(-) Y653/654F-hFGFR1 mutant and the TK(+) Y463F-hFGFR1 mutant were both ineffective. Analysis of the expression of early and late cardiac markers in differentiating EBs confirmed these observations. At variance with cardiomyocyte differentiation, all the transduced TK(+) FGFR1 forms were able to rescue haematopoietic differentiation in EBs originated by infected fgfr1(-/-) mESC, only the TK(-) Y653/654F-hFGFR1 mutant being ineffective. In keeping with these observations, treatment with different signalling pathway inhibitors indicates that protein kinase C and ERK activation are essential for cardiomyocyte but not for haematopoietic differentiation in EBs generated by fgfr1(+/-) approximately mESC. In conclusion, our results suggest that, although FGFR1 kinase activity is necessary for both cardiac and haematopoietic lineage maturation in mESC, phosphorylation of Y463 in the intracellular domain of the receptor is a specific requirement for cardiomyocyte differentiation

Fibroblast growth factor receptor-1 is essential for in vitro cardiomyocyte development

Abstract—Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling plays a crucial role in mesoderm formation and patterning. Heartless mutant studies in Drosophila suggest that FGFR1, among the different FGFRs, may play a role in cardiogenesis. However, fgfr1�/ � mice die during gastrulation before heart formation. To establish the contribution of FGFR1 in cardiac development, we investigated the capacity of murine fgfr1�/ � and fgfr1 �/ � embryonic stem (ES) cells to differentiate to cardiomyocytes in vitro. Clusters of pulsating cardiomyocytes were observed in �90 % of 3-dimensional embryoid bodies (EBs) originated from fgfr1�/ � ES cells at day 9 to 10 of differentiation. In contrast, 10% or less of fgfr1�/ � EBs showed beating foci at day 16. Accordingly, fgfr1 �/ � EBs were characterized by impaired expression of early cardiac transcription factors Nkx2.5 and d-Hand and of late structural cardiac genes myosin heavy chain (MHC)-�, MHC-�, and ventricular myosin light chain. Homozygous fgfr1 mutation resulted also in alterations of the expression of mesoderm-related early genes, including nodal, BMP2, BMP4, T(bra), and sonic hedgehog. Nevertheless, fgfr1 �/ � and fgfr1 �/ � EBs similarly express cardiogenic precursor, endothelial, hematopoietic, and skeletal muscle markers, indicating that fgfr1-null mutation exerts a selective effect on cardiomyocyte development in differentiating ES cells. Accordingly, inhibitors of FGFR signaling, including the FGFR1 tyrosine kinase inhibitor SU 5402, the MEK1/2 inhibitor U0126, and the protein kinase C inhibitor GF109 all prevented cardiomyocyte differentiation in fgfr1�/ � EBs without affecting the expression of the hematopoietic/endothelial marker flk-1. I

Persistence of ICD indication at the time of replacement in patients with initial implant for primary prevention indication: Effect on subsequent ICD therapies

AbstractBackgroundIndication to implantable cardioverter defibrillator (ICD) for primary prevention of sudden death relies on left ventricular ejection fraction (LVEF). We measured the proportion of patients in whom indication to ICD persisted at the time of generator replacement (GR) and searched for predictors of appropriate therapies after GR.MethodsWe identified all consecutive patients who had received an ICD at our hospital, for LVEF ≤35% and no previous arrhythmias or unexplained syncope. Then, we included the 166 patients who outlived their first device and underwent GR.ResultsAt the time of GR (mean follow-up 59 ± 20 months), ICD indication (i.e. LVEF ≤35% or previously treated ventricular arrhythmias) persisted in 114 (69%) patients. After GR, appropriate ICD therapies were delivered in 30 (26%) patients with persistent ICD indication and in 12 (23%) of the remaining patients (p = 0.656). Nonetheless, the annual rate of therapies was higher in the first group (1.08 versus 0.53 events/year; p < 0.001), as well as the rate of inappropriate therapies (0.03 versus 0 events/year; p = 0.031). The only independent predictor of appropriate ICD therapies after GR was the rate of shocks received before replacement (Hazard Ratio: 1.41; 95% confidence interval: 1.01–1.96; p = 0.041).ConclusionIn heart failure with reduced LVEF, ICD indication persisted at the time of GR in 69% of patients. However, even in the absence of persistent ICD indication at GR, the risk of recurrence of arrhythmic events was not null

Right ventricular septal pacing: Safety and efficacy in a long term follow up

AIM: To evaluate the safety and efficacy of the permanent high interventricular septal pacing in a long term follow up, as alternative to right ventricular apical pacing. METHODS: We retrospectively evaluated: (1) 244 patients (74 ± 8 years; 169 men, 75 women) implanted with a single (132 pts) or dual chamber (112 pts) pacemaker (PM) with ventricular screw-in lead placed at the right ventricular high septal parahisian site (SEPTAL pacing); (2) 22 patients with permanent pacemaker and low percentage of pacing (< 20%) (NO pacing); (3) 33 patients with high percentage (> 80%) right ventricular apical pacing (RVA). All patients had a narrow spontaneous QRS (101 ± 14 ms). We evaluated New York Heart Association (NYHA) class, quality of life (QoL), 6 min walking test (6MWT) and left ventricular function (end-diastolic volume, LV-EDV; end-systolic volume, LV-ESV; ejection fraction, LV-EF) with 2D-echocardiography. RESULTS: Pacing parameters were stable during follow up (21 mo/patient). In SEPTAL pacing group we observed an improvement in NYHA class, QoL score and 6MWT. While LV-EDV didn’t significantly increase (104 ± 40 mL vs 100 ± 37 mL; P = 0.35), LV-ESV slightly increased (55 ± 31 mL vs 49 ± 27 mL; P = 0.05) and LV-EF slightly decreased (49% ± 11% vs 53% ± 11%; P = 0.001) but never falling < 45%. In the RVA pacing control group we observed a worsening of NYHA class and an important reduction of LV-EF (from 56% ± 6% to 43% ± 9%, P < 0.0001). CONCLUSION: Right ventricular permanent high septal pacing is safe and effective in a long term follow up evaluation; it could be a good alternative to the conventional RVA pacing in order to avoid its deleterious effects

IntErnationaL eLeCTRicAl storm registry (ELECTRA): Background, rationale, study design, and expected results

Electrical storm (ES) is defined as three or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 h and is associated with an increased cardiac and all-cause mortality. ES is a full arrhythmic emergency, its prevalence steadily increasing along with the number of implantable cardioverter-defibrillator implanted every year in developed countries. Nowadays, little evidence exists regarding clinical predictors of ES and their potential association on mortality and heart failure (HF), nor optimal pharmacological and non-pharmacological treatment has ever been codified. The intErnationaL eLeCTRicAl storm registry (ELECTRA) is a multicentre, observational, prospective clinical study with two major aims. First, to create an international database on ES encompassing clinical features, pharmacological management, and interventional treatment strategies. Second, to describe mortality and rehospitalization rates in patients with ES over a long follow-up. The primary endpoint is all-cause mortality 3 years after the ES index event. The main secondary endpoint is hospitalization for all causes 3 years after the ES index event. Other secondary endpoints includes ES recurrences, unclustered VTs/VFs recurrences, and hospitalizations for HF worsening. A minimum of 500 patients will be included in the registry, and all patients will be followed-up for a minimum of three years. The present paper describes the background and current rationale of the ELECTRA study and details the study design, from enrolment strategy to data collection methods to planned data analysis. A brief overview of the expected results and their potential clinical and research implications will also be presented (NCT02882139). Keywords: Arrhythmia, Catheter ablation, Electrical storm, Implantable cardioverter-defibrillator, Ventricular fibrillation, Ventricular tachycardi

Cerebral collateral flow defines topography and evolution of molecular penumbra in experimental ischemic stroke

International audienceIntracranial collaterals are dynamically recruited after arterial occlusion and are emerging as a strong determinant of tissue outcome in both human and experimental ischemic stroke. The relationship between collateral flow and ischemic penumbra remains largely unexplored in pre-clinical studies. The aim of the present study was to investigate the pattern of collateral flow with regard to penumbral tissue after transient middle cerebral artery (MCA) occlusion in rats. MCA was transiently occluded (90min) by intraluminal filament in adult male Wistar rats (n=25). Intracranial collateral flow was studied in terms of perfusion deficit and biosignal fluctuation analyses using multi-site laser Doppler monitoring. Molecular penumbra was defined by topographical mapping and quantitative signal analysis of Heat Shock Protein 70kDa (HSP70) immunohistochemistry. Functional deficit and infarct volume were assessed 24h after ischemia induction. The results show that functional performance of intracranial collaterals during MCA occlusion inversely correlated with HSP70 immunoreactive areas in both the cortex and the striatum, as well as with infarct size and functional deficit. Intracranial collateral flow was associated with reduced areas of both molecular penumbra and ischemic core and increased areas of intact tissue in rats subjected to MCA occlusion followed by reperfusion. Our findings prompt the development of collateral therapeutics to provide tissue-saving strategies in the hyper-acute phase of ischemic stroke prior to recanalization therapy