Evidence for progressive reduction and loss of telocytes in the dermal cellular network of systemic sclerosis.

Telocytes, a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including human skin. Systemic sclerosis (SSc, scleroderma) is a complex connective tissue disease characterized by fibrosis of the skin and internal organs. We presently investigated telocyte distribution and features in the skin of SSc patients compared with normal skin. By an integrated immunohistochemical and transmission electron microscopy approach, we confirmed that telocytes were present in human dermis, where they were mainly recognizable by their typical ultrastructural features and were immunophenotypically characterized by CD34 expression. Our findings also showed that dermal telocytes were immunophenotypically negative for CD31/PECAM-1 (endothelial cells), α-SMA (myofibroblasts, pericytes, vascular smooth muscle cells), CD11c (dendritic cells, macrophages), CD90/Thy-1 (fibroblasts) and c-kit/CD117 (mast cells). In normal skin, telocytes were organized to form three-dimensional networks distributed among collagen bundles and elastic fibres, and surrounded microvessels, nerves and skin adnexa (hair follicles, sebaceous and sweat glands). Telocytes displayed severe ultrastructural damages (swollen mitochondria, cytoplasmic vacuolization, lipofuscinic bodies) suggestive of ischaemia-induced cell degeneration and were progressively lost from the clinically affected skin of SSc patients. Telocyte damage and loss evolved differently according to SSc subsets and stages, being more rapid and severe in diffuse SSc. Briefly, in human skin telocytes are a distinct stromal cell population. In SSc skin, the progressive loss of telocytes might (i) contribute to the altered three-dimensional organization of the extracellular matrix, (ii) reduce the control of fibroblast, myofibroblast and mast cell activity, and (iii) impair skin regeneration and/or repair.

Telocytes in Crohn's disease.

Crohn's disease (CD) is a relapsing chronic inflammatory disorder that may involve all the gastrointestinal tract with a prevalence of terminal ileum. Intestinal lesions have a characteristic discontinuous and segmental distribution and may affect all layers of the gut wall. Telocytes (TC), a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including gastrointestinal tract of humans and mammals. Several roles have been proposed for TC, including mechanical support, spatial relationships with different cell types, intercellular signalling and modulation of intestinal motility. The aim of our study was to investigate the presence and distribution of TC in disease-affected and -unaffected ileal specimens from CD patients compared with controls. TC were identified by CD34/PDGFRα immunohistochemistry. In affected CD specimens TC disappeared, particularly where fibrosis and architectural derangement of the intestinal wall were observed. In the thickened muscularis mucosae and submucosa, few TC entrapped in the fibrotic extracellular matrix were found. A discontinuous network of TC was present around smooth muscle bundles, ganglia and enteric strands in the altered muscularis propria. At the myenteric plexus, the loss of TC network was paralleled by the loss of interstitial cells of Cajal network. In the unaffected CD specimens, TC were preserved in their distribution. Our results suggest that in CD the loss of TC might have important pathophysiological implications contributing to the architectural derangement of the intestinal wall and gut dysmotility. Further functional studies are necessary to better clarify the role of TC loss in CD pathophysiology.

Effect of Chronic Kidney Disease on 5-Year Outcome in Patients With Heart Failure and Secondary Mitral Regurgitation Undergoing Percutaneous MitraClip Insertion.

Chronic kidney disease (CKD) is strongly related to outcomes in cardiovascular diseases. Limited data are available regarding the independent prognostic role of CKD after transcatheter mitral valve repair with MitraClip. We sought to evaluate the real impact of CKD in a large series of patients with heart failure (HF) and secondary mitral regurgitation (SMR) who underwent MitraClip treatment. The study included 565 patients with severe SMR from a multicenter international registry. Patients were stratified into 3 groups according to estimated glomerular filtration rate (eGFR) assessment before MitraClip implantation: normal eGFR (≥60 ml/min/1.73 m2) (n = 196), mild-to-moderate CKD (30 to 59 ml/min/1.73 m2) (n = 267), and severe CKD (<30 ml/min/1.73 m2) (n = 102). The primary end point was a composite of overall death and the first rehospitalization for HF, the secondary end points were overall death, cardiac death, and first rehospitalization for HF. CKD was present in about 2/3 of patients. At 5-year Kaplan-Meier analysis, primary clinical end point occurred in 60% of patients with normal eGFR, compared with 73% cases in patients with mild-to-moderate CKD and 91% in patients with severe CKD (p <0.001). Long-term overall death rate significantly decreased with increasing eGFR, and cardiac death and rehospitalization for HF rates. Multivariate Cox regression analysis identified severe CKD as the strongest independent predictor of adverse outcome (hazard ratio 2.136, 95% confidence interval 1.164 to 3.918, p = 0.014). In conclusion, CKD affected about 2/3 of patients who underwent MitraClip treatment for severe SMR, and it was a strong and independent predictor of 5-year adverse outcomes.

Prognostic Value of Pre-operative Atrial Fibrillation in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation.

Limited data are available regarding the independent prognostic role of preoperative atrial fibrillation (AF) after transcatheter mitral valve repair with MitraClip. We sought to evaluate the impact of preoperative AF in patients with heart failure (HF) and concomitant secondary mitral regurgitation (MR) after MitraClip treatment. The study included 605 patients with significant secondary MR from a multicenter international registry. Patients were stratified into 2 groups according to the presence or absence of preoperative AF. Primary end point was 5-year overall death, secondary end points were 5-year cardiac death and first re-hospitalization for HF. To account for baseline differences, patients were propensity score matched 1:1. The overall prevalence of preoperative AF was 44%. At 5-year Kaplan-Meier analysis, compared with patients without AF, those with AF had significantly more adverse events in term of overall death (67% vs 43%; HR 1.84, log-rank p <0.001) and cardiac death (56% vs 29%; HR 2.11, log-rank p <0.001) and re-hospitalization for HF (63% vs 52%; HR 1.33, log-rank p = 0.048). Multivariate analysis identified AF as independent predictor of worse outcome in term of primary end point (HR 1.729, 95% C.I. 1.060 to 2.821; p = 0.028). After propensity score matching, patients with AF had higher rates of death and cardiac mortality but similar rates of re-hospitalization for HF. In conclusion, in patients with HF undergoing MitraClip treatment for secondary MR, preoperative AF is common and an unfavourable predictor of 5-year death and cardiac death. However, AF did not affect the frequency of re-hospitalization for HF.

Mid-Term Clinical Outcomes Following Percutaneous Mitral Valve Edge-to-Edge Repair.

BACKGROUND: Approximately 50% of patients with severe mitral regurgitation (MR) referred for surgery have prohibitive surgical risk. MitraClip (Abbott Vascular) is an alternative therapy option in these patients. The aim of this study is to evaluate mid-term outcome in patients who underwent MitraClip implantation. METHODS: All consecutive patients with ≥2+ MR and high risk for conventional surgical therapy who underwent MitraClip implantation at our unit were included in the analysis. The primary endpoint was all-cause mortality and secondary endpoint was heart failure rehospitalization. RESULTS: From October 2008 to December 2016, a total of 162 patients underwent MitraClip procedure at our unit. The mean follow-up duration was 819.8 ± 671.1 days. Acute procedural success was achieved in 141 of 162 patients (87.0%) and was not significantly different between primary and secondary MR patients (P=.09). Mortality rates were 14.4%, 28.7%, 38.7%, and 49.3% at 1 year, 2 years, 3 years, and 5 years, respectively. Rehospitalization rates for heart failure were 21.7%, 34.3%, 44.2%, and 56.6% at 1 year, 2 years, 3 years, and 5 years, respectively. At follow-up, patients exhibited significant improvement in New York Heart Association functional classification (P<.001). On multivariate analysis, baseline left ventricular ejection fraction (LVEF) <30% (odds ratio, 6.62) and baseline MR severity (odds ratio, 3.40) were the strongest predictors of mortality. Primary MR (odds ratio, 0.20) was associated with lower risk of mortality compared with secondary MR. CONCLUSIONS: Treatment of MR with MitraClip results in significant symptomatic improvement with excellent short-term results. However, 5-year mortality was 49.3%; baseline LVEF <30% and MR severity are the strongest predictors of mortality, while primary MR was a predictor for lower risk of mortality when compared with secondary MR.

Multimodal imaging in the diagnosis and evaluation of intestinal malrotations in adults: a case report.

Midgut malrotation is a congenital anomaly referring to either lack of or incomplete rotation of the fetal intestines around the axis of the superior mesenteric artery during fetal development. It is rare in adulthood and the true incidence is difficult to estimate because most patients are asymptomatic. The diagnosis is usually performed with several radiological and surgical methods. We report a case of a woman who presented with cramp-like abdominal pain localized to the right iliac fossa. The patient underwent abdominal ultrasound, radiological examination without and with contrast, and computed tomography with three-dimensional volume rendering reconstruction. Although small bowel followthrough is often enough to recognize the type of malrotation, using multimodal imaging may offer a better definition of this abnormality with a better definition of the kind of malrotation, by adding additional anatomical information. In our case, the imaging clearly showed malrotation of the small bowel with reverse rotation of the colon. Hence a multimodal imaging strategy proved useful for the diagnosis of intestinal malrotation in an adult afflicted by chronic cramp-like abdominal pain.