Abstract Background Effect of statin therapy on coronary plaque stabilisation and reducing adverse cardiovascular events is well known both in primary and secondary prevention. Nevertheless, there is a paucity of data presenting the impact of statins on plaque morphology as assessed by optical coherence tomography (OCT). Purpose The goal of this analysis was to evaluate the plaque morphology using OCT within non-culprit, non-ischaemic coronary lesions in diabetes mellitus (DM) patients with or without statin pre-treatment. Methods All patients of the COMBINE (FFR-OCT) trial underwent fractional flow reserve (FFR) measurement followed by OCT in FFR negative lesions. OCT recorded the presence of thin-cap fibroatheroma (TCFA), plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN). Results From the 391 patients, 82 (21%) had no statin at baseline. OCT was performed in 463 lesions of which 96 lesions assessed in statin naive and 367 lesions in statin treated group. The median angiographic diameter stenosis was 50% and the median FFR value was 0.88 in both groups (p=0.953 and p=0.448, respectively). Myocardial infarction (MI) at presentation was 16.6% and did not differ between groups (p=0.380). Patients without statin pre-treatment were characterized by lower rate of known hypercholesterolemia (47.6% vs. 63.0%; p=0.011), male gender (52.4% vs. 65.7%; p=0.027), active smokers (8.5% vs. 22.3%; p=0.004) and previous MI (22.0% vs. 35.3%; p=0.022) as compared to patients with statin pre-treatment, respectively. The results of the qualitative OCT findings see in Table 1. Conclusions Non-ischemic lesions of DM patients without statin pre-treatment showed more vulnerable and instable plaque features like wider lipid arc, thinner fibrotic cap and a higher prevalence of lipid-rich plaque, TCFA and PR suggesting a stabilizing effect of statins on non-ischemic atherosclerotic lesions. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The trial is founded from the Department of Cardiology Zwolle Heart-centrum with support from a non-restricted grant from St Jude Medical (now Abbott)

Abstract Background Little is known about age-related differences in baseline atherosclerotic plaque morphology and composition in patients with diabetes mellites (DM). Purpose For this purpose, we studied DM patients from the Combine trial. Methods COMBINE (OCT-FFR, NCT02989740) is a multi-center, prospective study focusing on the natural history of non-ischemic, non-culprit coronary lesions and evaluate whether certain OCT-assessed variables could predict future adverse events originating from these lesions in a DM population. OCT analysis identifies plaque composition, estimates calcium arc (o), lipid arc (o), and measures thickness of the fibrous cap covering the lipid core. Moreover, OCT records the presence of typical plaque vulnerability traits like thin fibrous cap atheroma (TCFA), plaque erosion (PE), plaque rupture (PR), calcification nodule (CN), heterogeneous tissues (a probably healed plaque rupture), and macrophages accumulation (bright spots). A dedicated software estimated the interpolated percentage area stenosis (AS, %) measuring the minimal lumen area (MLA) and reference vessel area. The present analysis reports the baseline morphology of these lesions respectively in young (<70 years) vs. old (≥70 years) DM patients. Results OCT imaging was performed in 300 patients (361 lesions) from the COMBINE study, of which 203 lesions assessed in young and 158 lesions in old DM patients. There were no significant differences in MLA (mm2) 2.40 (1.85–315 vs. 2.30 (1.80–3.00), p=0.92), lesions length (mm 24.11 (15.10–33.10) vs. 24.20 (15.10–35.10), p=0.78), AS% (%) 63 (1.85–3.15) vs. 64 (56–73), p=0.41; lipid arc (o), 182 (140–250) vs. 175 (128–240), p=0.35), fibrous cap thickness covering the lipid arc (μm), 117 (65–193) vs. 110 (64–168), p=0.45, in the prevalence of TCFA 37 (18%) vs. 33 (21%), p=0.53, PR 17 (18%) vs. 15 (10%), p=0.71, heterogenous tissue 39 (19%) vs. 31 (20%), p=0.92, and bright spots 98 (48%) vs. 69 (44%), p=0.38. The patients ≥70 years had a higher prevalence of calcified plaques 171 (84%) vs. 143 (90%), p=0.08 and wider calcium arc. These lesions included more PE 7 (3%) vs. 13 (8%), p=0.05, CN 73 (36%) vs. 75 (47%), p=0.03, and CN associated with overlying thrombus 11 (5%) vs. 20 (13%), p=0.02. Conclusion Non-ischemic, non-culprit lesions in elderly DM patients present the same prevalence of soft, vulnerable plaques as it is a younger cohort, however, they have a higher prevalence of calcified plaque including complex calcified plaques as eroded plaques and calcification nodules with overlying thrombus. Whether these complex calcified plaques are associated with a higher risk of adverse events remains questionable and could be further elucidated from longer follow-up data of the COMBINE trial.

Cardiomyopathy in Fabry disease / There is no sweet spot in diabetes 461Amp V2, LVH Score, Q Dur V1, QT Dispersion and Spatial QRS-T angle for the discrimination between the groups.A discriminant score (normalized between 0 and 100) by patient was then set up using the variable coefficients of the models determined from a training set of 80% of both groups.The Logistic model was ultimately selected and led to a 2x2 classification (Table 1) in a test sample of the remaining 20% of the groups giving a 99.1% sensitivity for classifying normal patients and 69.1% sensitivity for correctly classifying Fabry patients.Bootstrap simulations displayed an acceptable stability of the decision rule.Conclusions: Novel ECG parameters identified via a two discriminant stepwise statistical approach may be useful for detection of FD patients with cardiac involvement.These data need to be confirmed in a prospective setting and through a comparison of FD patients with cardiac involvement versus non-FD-associated cardiomyopathy.

BACKGROUND:Lymphoplasmacytic plaque (LPP) is a recently described rare skin disease characterized by a dense dermal lymphohistiocytic infiltrate with polyclonal plasma cells. The clinical picture is distinct with reddish to brownish plaque with a predilection for the lower leg. LPP typically affects children.OBJECTIVE:To define clinical and histologic criteria of LPP and to develop a diagnostic flow chart.METHODS:We investigated six of our own LPP cases. Immunoglobulin light chains, IgG, IgG4, CD31, CD163 as a histiocytic marker were examined by immunohistochemistry. PCR-based molecular studies were conducted for borrelia sp., mycobacterial and leishmania sp. Moreover, 10 cases, which have been reported in the literature, were checked for the same features.RESULTS:We could differentiate three main histological patterns (superficial band-like only, [deep] dermal only and mixed). Acanthosis and interface dermatitis are key features in cases with a superficial band-like or mixed infiltrate. Granulomas and giant cells could be only found in about 30% of the cases. The number of plasma cells was variable accounting for 5-40% of the infiltrate. The number of blood vessels was increased in the majority of the cases. 'Free-floating' collagen bundles surrounded by histiocytes (pseudorosettes) were identified as a new histological feature. An infectious agent could be excluded in all cases.CONCLUSIONS:LPP is a long-standing skin disease, which may also occur in adults and in other body regions than the lower leg. Reproducible clinical and histological criteria allow delineating a diagnostic work-up for LPP.

Mitral annular velocity may be measured angle independently by speckle tracking echocardiography (STE), in contrast with tissue Doppler imaging (TDI). The purpose of the current study was to compare STE and TDI, with respect to 1) the accuracy of velocity measurements in a moving phantom, 2) the feasibility and reproducibility of measurement of mitral annular velocities in a clinical setting, and 3) the estimation of left ventricular filling pressures using mitral annular velocities.The velocity of a moving phantom, using different angles of insonation, and mitral annular velocities of 80 nonselected patients and 50 healthy volunteers were determined using TDI and STE. A subgroup of 20 patients was studied during right-sided heart catheterization.When the motion direction of the phantom was parallel to the ultrasound beam, both TDI and STE determined velocities accurately. With increasing angle of insonation, TDI-derived velocity decreased, whereas STE-derived velocity remained unchanged. The feasibility of mitral annular velocities measured by TDI and STE was comparable (98% vs 95%, P = not significant). Although for both techniques correlations between measured mitral annular velocities at repeated examinations were good, the test-retest variability of mitral annular velocities by TDI was higher. E/Em ratio by STE correlated better to pulmonary capillary wedge pressure (R(2) = 0.51, P < .001) compared with E/Em ratio derived from TDI (R(2) = 0.35, P < .01), although the difference in correlation was not statistically significant because of the limited sample size.Tissue velocities can be accurately determined by STE in a moving phantom and are angle independent, in contrast with TDI measurements. Furthermore, STE is a feasible and better reproducible method for the assessment of mitral annular velocities in a clinical setting.

The dynamic interaction between subendocardial and subepicardial fibre helices in the left ventricle (LV) leads to a twisting deformation, which has an important role in LV function. This study sought to assess the influence of cardiac shape on LV twist in the normal and dilated human heart. The study comprised 45 dilated cardiomyopathy (DCM) patients and 60 for age- and gender-matched healthy volunteers. Speckle tracking echocardiography was used to determine basal and apical LV peak systolic rotation (Rot(max)) and instantaneous LV peak systolic twist (Twist(max)). LV sphericity index was calculated by dividing the LV maximal long-axis internal dimension by the maximal short-axis internal dimension at end-diastole. A parabolic relation between the sphericity index and apical Rot(max) or Twist(max) was identified in the total study population (R(2) = 0.56 and R(2) = 0.54, respectively; both P < 0.001) and healthy volunteers (R(2) = 0.39 and R(2) = 0.25, respectively; both P < 0.001), whereas these relations were linear in DCM patients (R(2) = 0.40 and R(2) = 0.43, respectively; both P < 0.001). In a multivariate analysis, LV sphericity index was the strongest independent predictor of apical Rot(max) and Twist(max). In conclusion, LV apical rotation and twist are significantly influenced by LV configuration. Taking the important function of LV twist into account, this finding highlights the vital influence of cardiac shape on LV systolic function.

Scleroderma may present as being strictly limited to the skin, as in morphea, or within a multiorgan disease, as in systemic sclerosis. Accordingly, cutaneous manifestations vary clinically. In nodular or keloidal scleroderma, patients develop lesions that are clinically indistinguishable from a keloid; however, the histopathological findings are more variable. We describe a 16-year-old girl with morpheic lesions for 3–4 years and additional development of keloidal nodules within these lesions. The histological examination revealed a hypertrophic scar besides morphea.

Journal of the European Academy of Dermatology and VenereologyVolume 22, Issue 5 p. 631-633 Successful therapy of a patient with therapy recalcitrant generalized bullous scleroderma by extracorporeal photopheresis and mycophenolate mofetil M Schlaak, Corresponding Author M Schlaak *Corresponding author, University Hospital Leipzig, Department of Dermatology, Venerology and Allergology, Philipp-Rosenthal-Str. 23–25, 04103 Leipzig, Germany. tel. +49 341 97 18 750; fax +49 341 97 18 759; E-mail: [email protected]Search for more papers by this authorH Friedlein, H Friedlein Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorF Kauer, F Kauer Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorR Renner, R Renner Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorC Rogalski, C Rogalski Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorJC Simon, JC Simon Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this author M Schlaak, Corresponding Author M Schlaak *Corresponding author, University Hospital Leipzig, Department of Dermatology, Venerology and Allergology, Philipp-Rosenthal-Str. 23–25, 04103 Leipzig, Germany. tel. +49 341 97 18 750; fax +49 341 97 18 759; E-mail: [email protected]Search for more papers by this authorH Friedlein, H Friedlein Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorF Kauer, F Kauer Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorR Renner, R Renner Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorC Rogalski, C Rogalski Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this authorJC Simon, JC Simon Department of Dermatology, Venerology and Allergology, University Hospital Leipzig, Leipzig, GermanySearch for more papers by this author First published: 06 August 2007 https://doi.org/10.1111/j.1468-3083.2007.02403.xCitations: 22 Dr. Schlaak had full access to all of the data and takes responsibility for the integrity of the data and the accuracy of the data analysis. Funding support should be divided between those relevant to this manuscript and all other relationships. The sponsors had no role in the design and conduct of the study, in the collection, analysis, and interpretation of data, or in the preparation of the manuscript, review, or approval of the manuscript. DOI: 10.1111/j.1468-3083.2007.02403.x Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume22, Issue5May 2008Pages 631-633 RelatedInformation

BACKGROUND/OBJECTIVE:Left ventricular (LV) twist has an important role in LV function. The influence of the pattern of LV hypertrophy on LV twist in hypertrophic cardiomyopathy (HCM) patients is unknown. This study sought to assess LV twist in a large group of HCM patients according to the pattern of LV hypertrophy.METHODS:The final study population consisted of 43 patients with HCM (mean age 43 (15) years, 31 men) and a typical sigmoidal (n = 16) or reverse septal curvature (n = 27) and 43 age-matched and gender-matched healthy control subjects. LV peak systolic rotation (Rot(max)), LV peak systolic twist (Twist(max)) and untwisting at 5%, 10% and 15% of diastole were determined by speckle tracking echocardiography (STE).RESULTS:Compared to control subjects, HCM patients had increased basal Rot(max) (-5.5 degrees (2.3 degrees ) vs -3.4 degrees (1.7 degrees ), p<0.001) and comparable apical Rot(max) (7.3 degrees (3.1 degrees ) vs 7.0 degrees (2.2 degrees ), p = NS), resulting in increased Twist(max) (12.4 degrees (4.0 degrees ) vs 9.9 degrees (2.7 degrees ), p<0.01). Untwisting at 5%, 10% and 15% of diastole was decreased in HCM patients (all p<0.05). There was a striking difference in apical Rot(max )(9.4 degrees (2.8 degrees ) vs 6.0 degrees (2.6 degrees ), p<0.01) and Twist(max) (15.3 degrees (3.2 degrees ) vs 10.6 degrees (3.3 degrees ), p<0.01) between HCM patients with a sigmoidal and reverse septal curvature.CONCLUSIONS:STE may provide novel non-invasive indices to assess LV function in patients with HCM. Apical Rot(max) and Twist(max) in HCM patients are dependent on the pattern of LV hypertrophy.

Y-G. F ENG S-S . TAN X-Y. WANG* S-X . X IAO H. WANG H-Q. J I A J -W. WU D-L . HE* R-H. KANG Department of Dermatology, the Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, China *Institute of Urology, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi’an Jiaotong University, Xi’an, Shaanxi, China Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China Department of Dermatology, the Fourth Clinical Medical College of Hebei Medical University, Shijiazhuang, China Correspondence: Yi-Guo Feng. E-mail: fengyiguo70@163.com

In skin, an evolving inflammatory or immune response is triggered by early release of a cytokine cascade into the extracellular space. Investigation of extracellular cytokine secretion in situ has been limited by low cut-off filtering membranes and sample volume size and the inability to monitor changes in cytokine protein levels in real-time in situ. Here, we combine for the first time the methods of intradermal microdialysis and antibody protein arraying to profile the early cascade of multiple cytokines in a complex inflammatory response exemplified by ultraviolet B (UVB)-induced inflammation. We observed significant differences of the cytokine and growth factor responses after tissue injury by catheter placement and UVB-induced inflammation. UVB irradiation initiates a rapid proinflammatory response followed by a mixed TH1/TH2 response in which ultimately TH2 cytokines IL-4 and IL10 predominated after 24 h. This most likely indicates the termination and self limitation of the inflammatory response. We conclude that the combination of dermal microdialysis and protein microarray offers a powerful tool to analyze in real-time the complex and rapidly changing interstitial protein milieu during cutaneous inflammatory responses.