Screening for Type 1 Diabetes Risk in Newborns: The Freder1k Pilot Study in Saxony.

An increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB1*03 (DR3), HLA DRB1*04 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.

Psychological well-being and independent living of young adults with childhood-onset craniopharyngioma.

AIM: To assess the psychological well-being and social integration of adults with craniopharyngioma diagnosed in childhood. METHOD: A cross-sectional study of a nationwide cohort of young adults with craniopharyngioma in Germany was performed. A structured questionnaire covered the sociodemographic, clinical data, and subjective effects of the condition on social integration. Psychological well-being was assessed using the Hospital Anxiety and Depression Scale (HADS). Results were compared to young adults with type 1 diabetes mellitus (T1DM). RESULTS: The study included 59 participants (29 females, 30 males; mean age 25y 2mo [SD 5y 10mo]), mean age at first surgery 10y 2mo [SD 3y 7mo]. Compared to the T1DM group, significantly more young people with craniopharyngioma aged 25 to 35 years lived at their parents' homes (craniopharyngioma 43.34%; T1DM 13.7%; χ2 =4.14, p=0.049), and fewer lived in a relationship (craniopharyngioma 8.69%; T1DM 54.7%; χ2 =15.74, p<0.001). The HADS revealed a score for depression above the cut-off in 20.69 per cent of young adults with craniopharyngioma and in 6 per cent of young adults with T1DM (χ2 =13.42, p<0.001). INTERPRETATION: Young adults with craniopharyngioma reported subjective disadvantages in professional and social integration. Further, they presented with reduced well-being and increased depression rates. Better psychosocial support and self-management education might reduce the long-term burden of the disease.

The Human Tau Interactome: Binding to the Ribonucleoproteome, and Impaired Binding of the Proline-to-Leucine Mutant at Position 301 (P301L) to Chaperones and the Proteasome.

The tau protein is central to the etiology of several neurodegenerative diseases, including Alzheimer's disease, a subset of frontotemporal dementias, progressive supranuclear palsy and dementia following traumatic brain injury, yet the proteins it interacts with have not been studied using a systematic discovery approach. Here we employed mild in vivo crosslinking, isobaric labeling, and tandem mass spectrometry to characterize molecular interactions of human tau in a neuroblastoma cell model. The study revealed a robust association of tau with the ribonucleoproteome, including major protein complexes involved in RNA processing and translation, and documented binding of tau to several heat shock proteins, the proteasome and microtubule-associated proteins. Follow-up experiments determined the relative contribution of cellular RNA to the tau interactome and mapped interactions to N- or C-terminal tau domains. We further document that expression of P301L mutant tau disrupts interactions of the C-terminal half of tau with heat shock proteins and the proteasome. The data are consistent with a model whereby a higher propensity of P301L mutant tau to aggregate may reflect a perturbation of its chaperone-assisted stabilization and proteasome-dependent degradation. Finally, using a global proteomics approach, we show that heterologous expression of a tau construct that lacks the C-terminal domain, including the microtubule binding domain, does not cause a discernible shift of the proteome except for a significant direct correlation of steady-state levels of tau and cystatin B.

Mesonephric adenocarcinoma of the vagina : Diagnosis and multimodal treatment of a rare tumor and analysis of worldwide experience.

BACKGROUND: Mesonephric adenocarcinoma of the vagina is an extremely rare tumor of the female genital tract, with only a few cases reported so far worldwide. Consequently, there is no established standard treatment and limited knowledge about the prognosis and biologic behavior of vaginal mesonephric adenocarcinoma. METHODS: This report documents a new case of vaginal mesonephric adenocarcinoma diagnosed in a 54-year-old woman, and analyzes this in the context of all previously published cases. RESULTS: MRI demonstrated that the 2.5 × 1.8 cm tumor of the vaginal wall was invading urethra and bladder. Following surgical excision, histologic analysis determined mesonephric adenocarcinoma of the vagina, stage pT2 R1. In order to avoid the mutilating extended surgery which would be required to reach R0 and considerable impairment of quality of life, adjuvant radiochemotherapy was administered with external radiation and brachytherapy, including 5 cycles of cisplatin (40 mg/m²) for radiosensitization. After 4 years of continuous oncologic follow-up, the patient is alive and clinically free of disease. CONCLUSION: In this case it was shown that adjuvant radiochemotherapy with radiation and brachytherapy was effective to manage the surgical R1 situation and maintain the patient's life quality. More published cases reports are needed to gradually substantiate optimal treatment strategies.

Gremlin-1 identifies fibrosis and predicts adverse outcome in patients with heart failure undergoing endomyocardial biopsy.

BACKGROUND: Gremlin-1 (Grem1), an antagonist of bone morphogenetic proteins, is involved in fibrotic tissue formation in kidney and lung. The impact of myocardial Grem1 expression is unknown. We investigated the prognostic value of Grem1 expression in 214 consecutive patients with nonischemic heart failure (HF) undergoing endomyocardial biopsy. METHODS: In all patients, the following risk factors were assessed: Grem1 expression (semiquantitative score scheme ranging from 1 to 4), presence of inflammatory markers, detection of viral genome, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association functional class (NYHA), troponin I, and B-type natriuretic peptide. Degree of myocardial fibrosis was defined as an index. Study end point was a combination of all-cause death and HF-related rehospitalization within 3 years of follow-up. RESULTS: Grem1 expression significantly correlated with the degree of myocardial fibrosis (correlation coefficient r = 0.619; P < .0001). Patients with the highest Grem1 expression (score 4) showed the most severely impaired LVEF and highest LVEDD (P < .0001 and P = .030, respectively, for comparison of semiquantitative scores). During follow-up, 33 patients (15.4%) reached the study end point. Grem1 expression and NYHA ≥II were independent predictors of the end point (Grem1: hazard ratio [HR] 7.5, 95% confidence interval [CI] 1.8-32.2; P = .006; NYHA ≥II: HR 2.0, 95% CI 1.0-4.1; P = .048). CONCLUSIONS: Grem1 correlates with the degree of myocardial fibrosis and left ventricular dysfunction and is an independent predictor of adverse outcome in patients with nonischemic HF.

International longitudinal registry of patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the FIELD (GARFIELD).

BACKGROUND: Atrial fibrillation (AF) is associated with high rates of morbidity and mortality. Patients with AF carry a fivefold increased risk of stroke and the risk of death from AF-related stroke is doubled. Current management is often inadequate, leaving patients at risk for a potentially fatal or disabling event. The purpose of the GARFIELD registry is to evaluate the management and outcomes of patients with newly diagnosed non-valvular AF at risk for stroke. DESIGN: The GARFIELD registry is an observational, multicenter, prospective study of patients with newly diagnosed AF and one or more additional risk factors for stroke. The aim is to enroll 55,000 patients at >1,000 centers in 50 countries. Enrollment will take place in five independent, sequential, prospective cohorts. An additional retrospective validation cohort of 5,000 patients with established AF and at least one additional risk factor for stroke will be conducted in parallel with cohort one. The study started in December 2009, with a planned recruitment period of 4 years and a minimum of 2-year follow-up for each patient. SUMMARY: The GARFIELD registry will provide valuable insights into the clinical management and related outcomes of AF patients throughout many regions of the world and across the spectrum of healthcare systems. By capturing data from unselected patients treated in everyday practice, the registry has the potential to identify best practices as well as deficiencies in available treatment options for specific patient populations and to describe how therapeutic strategies, patient care, and outcomes will evolve over time.

Junctional adhesion molecule A expressed on human CD34+ cells promotes adhesion on vascular wall and differentiation into endothelial progenitor cells.

OBJECTIVE: To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34(+) cells into endothelial progenitor cells. METHODS AND RESULTS: Tissue healing and vascular regeneration is a multistep process requiring firm adhesion of circulating progenitor cells to the vascular wall and their further differentiation into endothelial cells. The role of JAM-A in platelet-mediated adhesion of progenitor cells was investigated by adhesion assays in vitro and with the help of intravital fluorescence microscopy in mice. Preincubation of human CD34(+) progenitor cells with soluble JAM-A-Fc (sJAM-A-Fc) resulted in significantly decreased adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Human CD34(+) cells express JAM-A, as defined by flow cytometry and Western blot analysis. JAM-A mediates differentiation of CD34(+) cells to endothelial progenitor cells and facilitates CD34(+) cell-induced reendothelialization in vitro. Pretreatment of human CD34(+) cells with sJAM-A-Fc resulted in increased neointima formation 3 weeks after endothelial denudation in the carotid arteries of nonobese diabetic/severe combined immunodeficient mice. CONCLUSIONS: These results indicate that the expression of JAM-A on CD34(+) cells mediates adhesion to the vascular wall after injury and differentiation into endothelial progenitor cells, a mechanism potentially involved in vascular regeneration. Human CD34(+) cells express JAM-A, mediating their interaction with platelets and endothelial cells. Specifically, JAM-A expressed on human CD34(+) progenitor cells regulates their adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Moreover, it mediates differentiation of CD34(+) cells to endothelial progenitor cells and facilitates reendothelialization.

Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells.

BACKGROUND: Peripheral homing of progenitor cells in areas of diseased organs is critical for tissue regeneration. The chemokine stromal cell-derived factor-1 (SDF-1) regulates homing of CD34+ stem cells. We evaluated the role of platelet-derived SDF-1 in adhesion and differentiation of human CD34+ cells into endothelial progenitor cells. METHODS AND RESULTS: Adherent platelets express substantial amounts of SDF-1 and recruit CD34+ cells in vitro and in vivo. A monoclonal antibody to SDF-1 or to its counterreceptor, CXCR4, inhibits stem cell adhesion on adherent platelets under high arterial shear in vitro and after carotid ligation in mice, as determined by intravital fluorescence microscopy. Platelets that adhere to human arterial endothelial cells enhance the adhesion of CD34+ cells on endothelium under flow conditions, a process that is inhibited by anti-SDF-1. During intestinal ischemia/reperfusion in mice, anti-SDF-1 and anti-CXCR4, but not isotype control antibodies, abolish the recruitment of CD34+ cells in microcirculation. Moreover, platelet-derived SDF-1 binding to CXCR4 receptor promotes platelet-induced differentiation of CD34+ cells into endothelial progenitor cells, as verified by colony-forming assays in vitro. CONCLUSIONS: These findings imply that platelet-derived SDF-1 regulates adhesion of stem cells in vitro and in vivo and promotes differentiation of CD34+ cells to endothelial progenitor cells. Because tissue regeneration depends on recruitment of progenitor cells to peripheral vasculature and their subsequent differentiation, platelet-derived SDF-1 may contribute to vascular and myocardial regeneration.

New approach for detection of LDL-hypercholesterolemia in the pediatric population: The Fr1dolin-Trial in Lower Saxony, Germany.

BACKGROUND AND AIMS: Lipid disorders are often detected very late, particularly in affected young children. We evaluated the feasibility of a screening for LDL-hypercholesterolemia (highLDL) among toddlers and preschoolers. METHODS: Population-based screening has been offered to all children (2-6 years) living in the State of Lower Saxony, Germany, with capillary blood sampling for detection of elevated LDL-cholesterol (LDL-C ≥ 135 mg/dL). Positive results were confirmed by a second measurement. Follow-up in specialized centers, including disease specific counselling and extended diagnostics, as well as evaluation of psychological distress of the parents, is carried out longitudinally. RESULTS: Up to March 2018, 5656 children have participated in the screening program. 5069/5656 children have completed the screening for highLDL (52.0% boys; median age: 4.0 years [Interquartile range, IQR 3.0-5.1]; mother age: 35 years [IQR 31-38]; father's age: 37 years; [IQR 33-42]). HighLDL was identified in 112 children (2.2%; 40.2% boys; LDL-C 157.6 ±â€¯29.5 mg/dL, mean ±â€¯SD). In the total cohort, parents stated in 40.9% of the cases a positive family history for hyperlipidemia and in 29.9% a premature cardiovascular event. Children with highLDL had more often both risk factors in their family history; however, in 37% of them none of these factors were reported. CONCLUSIONS: The first results of the screening program showed its feasibility and revealed high prevalence of highLDL in the general population. Furthermore, a large proportion of families of affected children were not aware about their lipid disorders.

Multifactorial predictors and outcome variables of vision restoration training in patients with post-geniculate visual field loss.

PURPOSE: Systematic stimulation of the visual field border in patients with visual field loss after cerebral lesions improves visual function even years after the onset of partial blindness. However, computer-based training programs like Vision Restoration Training (VRT) are not equally effective in all patients. We therefore tested which factors determine training outcome and which visual and cognitive functions are changed by VRT. METHODS: Multiple outcome measures were predicted using a multifactorial regression approach. Nineteen patients with post-geniculate visual system lesions performed six months of VRT and underwent extensive testing before and after treatment, including visual field measurements, attention functions, and subjective parameters. RESULTS: Visual field size increased significantly during training, but a number of cognitive, especially attentional, variables also improved, as did subjective visual function. The size of areas of residual vision was the strongest predictor variable for visual field increase. Demographic and lesion-related variables had little influence on training success. CONCLUSIONS: With multivariate regression models, training outcome on different variables can be accurately predicted. Moreover, visual field increase is sufficiently predictable based on a set of variables readily available to the clinician: age of the patient, time since lesion, number of absolute perimetric defects, eccentricity of the visual field border, size of areas of residual vision, and average reaction time to perimetric stimuli.

Computer based vision restoration therapy in glaucoma patients: a small open pilot study.

PURPOSE: Several studies have shown that computer-based visual stimulation improves detection performance in brain damaged patients with post-chiasmatic lesions after stroke or trauma. Because it is not known whether visual field defects after retinal lesions can also be modified by visual stimulation we explored if visual field enlargements are possible in patients with glaucoma. METHODS: Five patients with primary open angle glaucoma (POAG) performed Vision Restoration Training (VRT), a computer-based vision training for a total of 6 months in two 3-months blocks with a 3-months training-free interval between the two training periods. Perimetric testing was performed with High Resolution Perimetry (HRP) as well as with 30 degrees and 70 degrees white/white (W/W) and 30 degrees blue/yellow (B/Y) conventional automatic perimetry (Oculus Twinfield). RESULTS: After the first 3 months of training the average detection performance significantly increased in HRP (Z= -2.023, p<0.05) and in 30 degrees W/W perimetry (Z= -2.023, p<0.05), but not in B/Y perimetry (Z= -1.214, p=0.225) or in the 70 degrees W/W perimetry, which included more peripheral, non-trained areas (Z= -0.406, p=0.684). Visual improvements remained stable after the training-free interval. Measured by HRP after the second VRT period 3 patients achieved an increase in the ability to detect visual stimuli, however, this improvement did not reach significance (Z= -1.826, p=0.068). CONCLUSIONS: While a small patient sample does not permit general conclusions on visual field recovery after glaucoma, this pilot study suggests that visual field defects caused by retinal lesion may be improved by systematic vision stimulation. A larger sample, randomized clinical trial is now warranted.

Vision- and health-related quality of life before and after vision restoration training in cerebrally damaged patients.

PURPOSE: The aim of the study was to examine if improvements of stimulus detection performance in visual field tests after intensive visual training of the visual field border zone in patients with visual field defects are associated with changes in self-reported vision- and health-related quality of life (QoL). METHODS: We studied a clinical sample of 85 patients suffering from visual field loss after brain damage that underwent repetitive, daily light stimulation (vision restoration training, VRT) of the visual field border and the blind visual field for up to 75 hrs (N=16) or 150 hrs (N=69). Stimulus detection was quantified in the central visual field with a campimetric method before and after intervention. Health-related QoL was assessed by the Health-Survey SF-36 and vision-related QoL by the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). RESULTS: Both vision- and health-related QoL measures improved after VRT. Significant increases were found in 8 out of 12 NEI-VFQ and 3 out of 8 SF-36 subscales. Of the 85 participants 6% showed a decrease in stimulus detection performance, 42% showed an increase of less than 5% detected stimuli, 24% showed an increase of 5-10% detected stimuli and 28% of more than 10% detected stimuli. Changes in campimetric stimulus detection rates were related to NEI-VFQ subscales point differences general vision (3 points), difficulty with near vision activities (4 points), limitations in social functioning due to vision (4 points) and driving problems (12 points). There was no relation of visual field changes to changes in SF-36 component and subscale scores. CONCLUSIONS: The NEI-VFQ is a valuable measure of self-reported visual impairment in patients with visual field defects. Stimulation of the visual field by training may lead to improvements of vision-related QoL which were correlated with the extent of visual field enlargements.

Long-term learning of visual functions in patients after brain damage.

PURPOSE: Systematic vision restoration training has been shown to improve the detection performance of brain-damaged patients with visual-field defects. So far, patients have been trained daily up to 6 months. We wished to determine whether intensive long-term training of 12 months further increases visual detection abilities. METHODS: Retrospective comparison of 17 patients with visual-field defects using vision restoration training for 12 months with a group of patients training for 6 months. Computer-based home training was completed for 6 months (about 195,000 stimuli presentations) or for 12 months (about 390,000 stimuli presentations). Visual fields were measured at baseline with Rodenstock Perimat 206 (monocular) at 90 degrees eccentricity and at 54 degrees eccentricity with high resolution perimetry (HRP) (binocular) after 6 months (post-6) and after 12 months (post-12) of training. RESULTS: Near-threshold perimetry revealed minor training effects, beyond 6 months, of 3.5% (p=0.099) in the right eye and of 1.5% (p=0.57) in the left eye. No effects of long-term training were evident in above threshold testing (0.8% detection improvement, n.s.). CONCLUSIONS: Learning to detect above-threshold stimuli in patients with post-retinal lesions is completed after 6 months of practice with only marginal improvements thereafter. Near-threshold testing reveals that peripheral areas of the visual-field benefit from long-term training even if they are not trained.

Mitral Valve Endocarditis due to Lactobacillus.

Lactobacillus species are Gram-positive, facultative anaerobic, rod-shaped bacteria. They belong to the lactic acid bacteria group and are also known as a usual part of the normal flora of the gastrointestinal tract as well as of the urinary and genital tracts. They are an infrequent human pathogen but can induce several infections such as bacteremia and infectious endocarditis. We report the case of an 81-year-old woman with Lactobacillus bacteremia and mitral valve endocarditis as well as splenic abscesses.

Galectin-3 is associated with left ventricular reverse remodeling and outcome after percutaneous mitral valve repair.

BACKGROUND: Plasma Galectin-3 is a marker of myocardial inflammation and fibrosis, was associated with left ventricular (LV) reverse remodeling after conventional surgical mitral valve repair (MVR) and predicted clinical events in patients undergoing transcatheter aortic valve replacement (TAVR). We aimed to evaluate the association between pre-interventional Galectin-3 levels and (1) reverse LV remodeling and (2) major adverse cardiovascular events (MACE) in patients undergoing percutaneous MVR. METHODS: Forty-four consecutive patients (median age 79 years, LV ejection fraction 39.5 ±â€¯11.4%, 91% in NYHA functional class ≥III) with symptomatic moderate to severe mitral regurgitation undergoing percutaneous MVR were prospectively included. Plasma Galectin-3 levels were measured before the procedure. Echocardiographic and clinical assessment was performed at baseline and after 3 months. LV reverse remodeling was prospectively defined as a ≥10% increase in global longitudinal strain. MACE included death, myocardial infarction, heart failure related rehospitalization and stroke and was assessed after a mean follow-up time of 2 years. RESULTS: 72.7% of the patients showed LV reverse remodeling. Pre-interventional Galectin-3 < 10 ng/ml was an independent predictor of LV reverse remodeling (OR 10.3, 95% CI 1.2-83.9, p = 0.036). 25 patients (56.8%) experienced a MACE. Patients with Galectin-3 levels ≥ 10 ng/ml had significantly more MACE than patients with Galectin-3 levels < 10 ng/ml (100% vs. 45.5%, p = 0.003). Diabetes independently predicted MACE (HR 3.1, 95% CI 1.0-9.4, p = 0.049); Galectin-3 ≥ 10 ng/ml was of borderline significance (HR 2.2, 95% CI 0.9-5.4, p = 0.088). CONCLUSIONS: Pre-interventional plasma Galectin-3 levels are associated with LV reverse remodeling and with clinical outcome after percutaneous MVR.

Recovery of visual field defects: a large clinical observational study using vision restoration therapy.

PURPOSE: In small experimental trials, vision restoration therapy (VRT), a home-based rehabilitation method, has shown to enlarge the visual field and improve reaction times in patients with lesion involving the CNS. We now evaluated the outcome of VRT in a large sample of clinical patients and studied factors contributing to subjective and objective measures of visual field alterations. METHODS: Clinical observational analysis of visual fields of 302 patients before and after being treated with computer-based vision restoration therapy for a period of 6 months at eight clinical centers in central Europe. The visual field defects were due to ischemia, hemorrhage, head trauma, tumor removal or anterior ischemic optic neuropathy. Primary outcome measure was a visual field assessment with super-threshold perimetry. Additionally, conventional near-threshold perimetry, eye movements and subjective reports of daily life activities were assessed in a subset of the patients. RESULTS: VRT improved patients' ability to detect super-threshold stimuli in the previously deficient area of the visual field by 17.2% and these detection gains were not significantly correlated with eye movements. Notable improvements were seen in 70.9% of the patients. Efficacy was independent of lesion age and etiology, but patients with larger areas of residual vision at baseline and patients>65 years old benefited most. Conventional perimetry validated visual field enlargements and patient testimonials confirmed the improvement in every day visual functions. CONCLUSIONS: VRT improves visual functions in a large clinical sample of patients with visual field defects involving the CNS, confirming former experimental studies.

Clinical and histopathological features of patients with systemic sclerosis undergoing endomyocardial biopsy.

BACKGROUND: Cardiac involvement in systemic sclerosis (SSc) is associated with a variable phenotype including heart failure, arrhythmias and pulmonary hypertension. The aim of the present study was to evaluate clinical characteristics, histopathological findings and outcome of patients with SSc and a clinical phenotype suggesting cardiac involvement. METHODS AND RESULTS: 25 patients with SSc and clinical signs of cardiac involvement were included between June 2007 and December 2010. They underwent routine clinical work-up including laboratory testing, echocardiography, left and right heart catheterization, holter recordings and endomyocardial biopsy. Primary endpoint (EP) was defined as the combination of cardiovascular death, arrhythmic endpoints (defined as appropriate discharge of implantable cardioverter defibrillator (ICD)) or rehospitalization due to heart failure. The majority of patients presented with slightly impaired left ventricular function (mean LVEF 54.1±9.0%, determined by echocardiography). Endomyocardial biopsies detected cardiac fibrosis in all patients with a variable area percentage of 8% to 32%. Cardiac inflammation was diagnosed as follows: No inflammation in 3.8%, isolated inflammatory cells in 38.5%, a few foci of inflammation in 30.8%, several foci of inflammation in 15.4%, and pronounced inflammation in 7.7% of patients. During follow up (FU) (22.5 months), seven (28%) patients reached the primary EP. Patients with subsequent events showed a higher degree of fibrosis and inflammation in the myocardium by trend. While patients with an inflammation grade 0 or 1 showed an event rate of 18.2%, the subgroup of patients with an inflammation grade 2 presented with an event rate of 25% versus an event rate of 50% in the subgroup of patients with an inflammation grade 3 and 4, respectively (p=0.193). Furthermore, the subgroup of patients with fibrosis grade 1 showed an event rate of 11%, patients with fibrosis grade 2 and 3 presented with an event rate of 33% and 42% respectively (p = 0.160). CONCLUSIONS: Patients with SSc and clinical signs of cardiac involvement presented with mildly impaired LVEF. Prognosis was poor with an event rate of 28% within 22.5 months FU and was associated with the degree of cardiac inflammation and fibrosis.

Effects of 2 different antiplatelet regimens with abciximab or tirofiban on platelet function in patients undergoing coronary stenting.

BACKGROUND: We sought to compare the antiplatelet effects of the glycoprotein IIb-IIIa receptor blockers abciximab or tirofiban, combined with an adjuvant therapy with clopidogrel and aspirin. STUDY DESIGN AND METHODS: Twenty patients undergoing coronary stenting were randomly assigned to receive either abciximab or tirofiban combined with aspirin and clopidogrel. Serial blood samples were taken to assess platelet aggregation, P-selectin expression, thrombin generation, and platelet-induced endothelial cell expression of MCP-1, uPAR, and ICAM-1. Results and conclusions The therapy with aspirin plus clopidogrel attenuated agonist-induced platelet aggregation and P-selectin surface exposure (P <.05 vs aspirin monotherapy). Both tirofiban and abciximab further reduced agonist-induced platelet aggregation (P <.05), and decreased thrombin generation but had no effect on platelet alpha-granule release. None of the antithrombotic strategies significantly affected platelet-induced endothelial cell activation. Since platelet adhesion/degranulation initiates an inflammatory/mitogenic response in the vascular wall, future therapeutic strategies will have to be aimed at the inhibition of platelet release reactions.

Cardiac magnetic resonance imaging in patients undergoing percutaneous mitral valve repair with the MitraClip system.

BACKGROUND: Percutaneous mitral valve repair (MVR) with the MitraClip(®) system in patients with mitral regurgitation (MR) is known to reduce symptoms and to improve cardiac morphology and function. MitraClip has been approved for cardiac magnetic resonance imaging (MRI). To date, however, no systematic analysis exists on cardiac MRI in patients undergoing the MitraClip procedure. OBJECTIVE: The aim of this study was to (1) prove feasibility and robustness of cardiac MRI and (2) visualize effects of the procedure on cardiac morphology and function by cardiac MRI. METHODS: 27 consecutive patients (age 77.5 ± 7.6 years) with symptomatic moderate to severe MR undergoing the MitraClip(®) procedure were prospectively included. Cardiac MRI at 1.5 T was performed before and at 3 months after intervention. Cardiac morphology and function were evaluated using steady-state free precession (SSFP) cine sequences by assessment of left ventricular enddiastolic and endsystolic diameters (LVEDD, LVESD) and volumes (EDV, ESV), ejection fraction (LVEF) and stroke volume (SV), diameter of mitral annulus, and myocardial mass (MM). Planimetry of the left atrium (LA) was performed in identical slices in a four-chamber view. RESULTS: Around the clip an extinction artifact was observed which did not disturb the evaluation of cardiac morphology and function. At follow-up, we observed significant decreases of LVEDD (58.0 to 53.3 mm, p < 0.0001), EDV (167 to 159 mL, p = 0.0006) and ESV (101 to 89 mL, p < 0.0001), diameter of mitral annulus (41.4 to 37.9 mm, p < 0.0001), myocardial mass (148.4 to 144.5 g, p = 0.0004) and LA size (40.2 to 37.6 cm(2), p < 0.0001). LVEF improved (43.3 to 46.7 %, p = 0.0041). CONCLUSIONS: Cardiac MRI is feasible and robust in patients with MitraClips. The clinical benefit of a successful MitraClip intervention is paralleled by significant improvements of cardiac morphology and function which can be monitored and validated using MRI in clinical follow-up examinations.