Appetite suppressants and valvular heart disease - a systematic review

Background Although appetite suppressants have been implicated in the development of valvular heart disease, the exact level of risk is still uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were affected, but subsequent research has yielded substantially different figures. Our objective was to systematically assess the risk of valvular heart disease with appetite suppressants. Methods We accepted studies involving obese patients treated with any of the following appetite suppressants: fenfluramine, dexfenfluramine, and phentermine. Three types of studies were reviewed: controlled and uncontrolled observational studies, and randomized controlled trials. Outcomes of interest were echocardiographically detectable aortic regurgitation of mild or greater severity, or mitral regurgitation of moderate or greater severity. Results Of the 1279 patients evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral regurgitation, respectively. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals 1.06 to 2.25, p = 0.02) with an attributable rate of 1.0%. Only one case of valvular heart disease was detected in 57 randomized controlled trials, but this was judged unrelated to drug therapy. Conclusions The risk of valvular heart disease is significantly increased by the appetite suppressants reviewed here. Nevertheless, when considering all the evidence, valvulopathy is much less common than suggested by the initial, less methodologically rigorous studies

Dynamics of trimming the content of face representations for categorization in the brain

To understand visual cognition, it is imperative to determine when, how and with what information the human brain categorizes the visual input. Visual categorization consistently involves at least an early and a late stage: the occipito-temporal N170 event related potential related to stimulus encoding and the parietal P300 involved in perceptual decisions. Here we sought to understand how the brain globally transforms its representations of face categories from their early encoding to the later decision stage over the 400 ms time window encompassing the N170 and P300 brain events. We applied classification image techniques to the behavioral and electroencephalographic data of three observers who categorized seven facial expressions of emotion and report two main findings: (1) Over the 400 ms time course, processing of facial features initially spreads bilaterally across the left and right occipito-temporal regions to dynamically converge onto the centro-parietal region; (2) Concurrently, information processing gradually shifts from encoding common face features across all spatial scales (e.g. the eyes) to representing only the finer scales of the diagnostic features that are richer in useful information for behavior (e.g. the wide opened eyes in 'fear'; the detailed mouth in 'happy'). Our findings suggest that the brain refines its diagnostic representations of visual categories over the first 400 ms of processing by trimming a thorough encoding of features over the N170, to leave only the detailed information important for perceptual decisions over the P300

Imaging myocardial carcinoid with T2-STIR CMR

We used T2-STIR (Short Tau Inversion Recovery) cardiovascular magnetic resonance to demonstrate carcinoid tumor metastases to the heart and liver in a 64-year-old woman with a biopsy-proven ileal carcinoid tumor who was referred because of an abnormal echocardiogram

A new shape for an old function: lasting effect of a physiologic surgical restoration of the left ventricle

BACKGROUND: Long-term morphofunctional outcome may vary widely in surgical anterior left ventricular wall restoration, suggesting variability in post-surgical remodeling similar to that observed following acute myocardial infarction. The aim of this pilot study was to demonstrate that surgical restoration obtained with a particular shape of endoventricular patch leads to steady morphofunctional ventricular improvement when geometry, volume and residual akinesia can be restored as normal as possible. METHODS: This study involved 12 consecutive patients with previous anterior myocardial infarction, dilated cardiomyopathy and no mitral procedures, who underwent left ventricular reconstruction and coronary revascularization between May 2002 and May 2003 using a small, narrow, oval patch aiming at a volume ≤ 45 mL/m(2 )with elliptical shape. Eleven geometric parameters were examined preoperatively and at least 3, 12 and 24 months after the operation by serial echocardiographic studies and evaluated by paired t test taking the time of surgery as a starting point for remodeling. RESULTS: All patients were in NYHA class 1 at follow-up. Patch geometry obtained a conical shape of the ventricle with new apex, physiologic rearrangement of functioning myocardial wall and small residual akinesia. Ventricular changes at the four time-points showed that all parameters improved significantly compared to preoperative values (end-diastolic volume = 184.2 ± 23.9 vs 139.9 ± 22.0, p = 0.001; vs 151.0 ± 33.8, p = 0.06; vs 144.9 ± 34.0, p = 0.38; end-systolic volume = 125.7 ± 20.6 vs 75.2 ± 14.1, p = 0.001; vs 82.1 ± 23.9, p = 0,18; vs 77.1 ± 19.4, p = 0.41) without further changes during follow-up except for wall motion score index (2.0 ± 0.2 to 1.7 ± 0.2, to 1.4 ± 0.2, to 1.3 ± 0.2) and percentage of akinesia (30.4 ± 7.5 to 29.3 ± 4.2, to 19.8 ± 11.6, to 14.5 ± 7.2) which slowly and significantly improved suggesting a positive post-surgery remodeling. CONCLUSION: Ventricular reconstruction caring of physiological shape, volume, revascularization and residual akinesia obtained a steady geometry. Positive remodeling and equalization of geometrical outcome may persistently prevent long-term redilation

Risk of valvular heart disease associated with use of fenfluramine

BACKGROUND: Estimates of excess risk of valvular heart disease among prior users of fenfluramine and dexfenfluramine have varied widely. Two major forms of bias appear to contribute to this variability and also result in a systematic under-estimation of risk. The first, a form of nondifferential misclassification, is the result of including background, prevalent cases among both exposed and unexposed persons in calculations of risk. The second bias results from not considering the relatively short duration of exposure to drugs. METHODS: We examined data from all available echocardiographic studies reporting the prevalence of aortic regurgitation (AR) and mitral regurgitation (MR) among persons exposed to fenfluramine or dexfenfluramine and a suitable control group. We also included one study in which previously existing AR or MR had been excluded. We corrected for background prevalent cases, estimated incidence rates in unexposed persons, and performed a person-years analysis of apparent incidence rates based on exposure time to provide an unbiased estimate of relative risk. RESULTS: Appearance of new AR was strongly related to duration of exposure (R(2 )= 0.75, p < 0.0001). The summary relative risk for mild or greater AR was 19.6 (95% CI 16.3 – 23.5, p < 0.00001); for moderate or greater MR it was 5.9 (95% CI 4.0 – 8.6, p < 0.00001). CONCLUSION: These findings provide strong support for the view that fenfluramine and dexfenfluramine are potent causal factors in the development of both aortic and mitral valvular heart disease

Pre-ejection period by radial artery tonometry supplements echo doppler findings during biventricular pacemaker optimization

<p>Abstract</p> <p>Background</p> <p>Biventricular (Biv) pacemaker echo optimization has been shown to improve cardiac output however is not routinely used due to its complexity. We investigated the role of a simple method involving computerized pre-ejection time (PEP) assessment by radial artery tonometry in guiding Biv pacemaker optimization.</p> <p>Methods</p> <p>Blinded echo and radial artery tonometry were performed simultaneously in 37 patients, age 69.1 ± 12.8 years, left ventricular (LV) ejection fraction (EF) 33 ± 10%, during Biv pacemaker optimization. Effect of optimization on echo derived velocity time integral (VTI), ejection time (ET), myocardial performance index (MPI), radial artery tonometry derived PEP and echo-radial artery tonometry derived PEP/VTI and PEP/ET indices was evaluated.</p> <p>Results</p> <p>Significant improvement post optimization was achieved in LV ET (286.9 ± 37.3 to 299 ± 34.6 ms, p < 0.001), LV VTI (15.9 ± 4.8 cm to 18.4 ± 5.1 cm, p < 0.001) and MPI (0.57 ± 0.2 to 0.45 ± 0.13, p < 0.001) and in PEP (246.7 ± 36.1 ms to 234.7 ± 35.5 ms, p = 0.003), PEP/ET (0.88 ± 0.21 to 0.79 ± 0.17, p < 0.001), and PEP/VTI (17.3 ± 7 to 13.78 ± 4.7, p < 0.001). The correlation between comprehensive echo Doppler and radial artery tonometry-PEP guided optimal atrioventricular delay (AVD) and optimal interventricular delay (VVD) was 0.75 (p < 0.001) and 0.69 (p < 0.001) respectively. In 29 patients with follow up assessment, New York Heart Association (NYHA) class reduced from 2.5 ± 0.8 to 2.0 ± 0.9 (p = 0.004) at 1.8 ± 1.4 months.</p> <p>Conclusion</p> <p>An acute shortening of PEP by radial artery tonometry occurs post Biv pacemaker optimization and correlates with improvement in hemodynamics by echo Doppler and may provide a cost-efficient approach to assist with Biv pacemaker echo optimization.</p

Hybrid suspension/solution precursor plasma spraying of a complex Ba(Mg1/3Ta2/3)O3 perovskite: Effects of processing parameters and precursor chemistry on phase formation and decomposition

Abstract: Ba(Mg1/3Ta2/3)O3 (BMT) has a high melting point and is envisioned as a thermal barrier coating material. In this study, a hybrid suspension/solution precursor plasma spray process with a radio frequency thermal plasma torch is designed to deposit BMT nanostructured coatings. Six combinations of chemical reagents are investigated as coating precursors: one BMT powder suspension and five Ta2O5 suspensions in nitrate- or acetate-based solutions. X-ray photoelectron spectroscopy is used to evaluate the element evaporation during plasma spraying, while a thermogravimetric/differential thermal analysis is applied to investigate the BMT formation. Parameters such as precursor chemistry, plasma power, spraying distance and substrate preheating are studied with regard to the coating phase structure. Twice the Mg stoichiometric amount with a power of 50 kW shows the best results when using nanocrystallized Ta2O5 as a tantalum precursor. When choosing nitrates as Ba and Mg precursors, crystallized BMT is obtained at lower plasma power (45 kW) when compared to acetates (50 kW). BaTa2O6, Ba3Ta5O15, Ba4Ta2O9, Mg4Ta2O9 are the main secondary phases observed during the BMT coatings deposition. Because of the complicated acetate decomposition process, the coating deposition rate from nitrate precursors is 1.56 times higher than that from acetate precursors

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines

Background: The mechanisms by which tumor-specific T cells induce regression of established metastases are not fully characterized. In using the poorly immunogenic B16BL6-D5 (D5) melanoma model we reported that T cell-mediated tumor regression can occur independently of perforin, IFN-gamma or the combination of both. Characterization of regressing pulmonary metastases identified macrophages as a major component of the cells infiltrating the tumor after adoptive transfer of effector T cells. This led us to hypothesize that macrophages played a central role in tumor regression following T-cell transfer. Here, we sought to determine the factors responsible for the infiltration of macrophages at the tumor site. Methods: These studies used the poorly immunogenic D5 melanoma model. Tumor-specific effector T cells, generated from tumor vaccine-draining lymph nodes (TVDLN), were used for adoptive immunotherapy and in vitro analysis of chemokine expression. Cellular infiltrates into pulmonary metastases were determined by immunohistochemistry. Chemokine expression by the D5 melanoma following co-culture with T cells, IFN-gamma or TNF-alpha was determined by RT-PCR and ELISA. Functional activity of chemokines was confirmed using a macrophage migration assay. T cell activation of macrophages to release nitric oxide (NO) was determined using GRIES reagent. Results: We observed that tumor-specific T cells with a type 1 cytokine profile also expressed message for and secreted RANTES, MIP-1 alpha and MIP-1 beta following stimulation with specific tumor. Unexpectedly, D5 melanoma cells cultured with IFN-gamma or TNF-alpha, two type 1 cytokines expressed by therapeutic T cells, secreted Keratinocyte Chemoattractant (KC), MCP-1, IP-10 and RANTES and expressed mRNA for MIG. The chemokines released by T cells and cytokine-stimulated tumor cells were functional and induced migration of the DJ2PM macrophage cell line. Additionally, tumor-specific stimulation of wt or perforin-deficient (PKO) effector T cells induced macrophages to secrete nitric oxide (NO), providing an additional effector mechanism for T cell-mediated tumor regression. Conclusion: These data suggest two possible sources for chemokine secretion that stimulates macrophage recruitment to the site of tumor metastases. Both appear to be initiated by T cell recognition of specific antigen, but one is dependent on the tumor cells to produce the chemokines that recruit macrophages