Mitral annuloplasty in patients with ischemic versus dilated cardiomyopathy

Objective: Mitral regurgitation is a frequent finding in patients with end-stage cardiomyopathy predicting poor survival. Conventional treatment consists medical treatment or cardiac transplantation. However, despite severely decreased left ventricular function, mitral annuloplasty may improve survival and reduce the need for allografts. Methods: From January 1996 to July 2002, 121 patients with severe end-stage dilated (DCM) or ischemic cardiomyopathy (ICM), mitral regurgitation ≥2, and left ventricular ejection fraction ≤30% underwent mitral valve annuloplasty using a flexible posterior ring. DCM was diagnosed in 30 patients (25%), whereas ICM was found in 91 patients (75%). Concomitant tricuspid valve repair was performed in 14 (46.6%) patients in the DCM, and in 11 (12%) in the ICM group (P=0.0001), coronary artery bypass grafting in three (10%) in the DCM, and in 78 patients (86%) in the ICM group (P<0.00001). The mean follow-up time was 567±74 days in the DCM and 793±63 days in the ICM group (ns). Results: Early mortality was 6.6% (8/121), and was equal for both groups. Improvement in NYHA class (DCM 3.3+0.1-1.8±0.16; ICM from 3.2+0.04 to 1.7±0.07) were equal between groups after 1 year. Seventeen (15%) late deaths occurred during the follow-up period. There was no difference in the 2-year actuarial survival between groups (DCM/ICM 0.93/0.85). Risk factors for mitral reconstruction failure, defined as regurgitation ≥2 after 1 year, were preoperative NYHA IV in the DCM group (P=0.03), a preoperative posterior infarction (P=0.025), decreased left ventricular function (P=0.043), larger ring size (P=0.026) and preoperative renal failure (P=0.05) in the ICM group. Risk factors for death were larger ring size (P=0.02) and an increased LVEDD (P=0.027) in the DCM group and the postoperative use of IABP (P=0.002), renal failure (P=0.001), and a larger preoperative LVESD (P=0.035) in the ICM group. Conclusion: Mitral reconstruction with a posterior annuloplasty using a flexible ring is effective in patients with severely depressed left ventricle function and has an acceptable operative mortality. Mid-term results are superior to medical treatment alone and comparable to cardiac transplantatio

Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68

<p>Abstract</p> <p>Background</p> <p>Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo.</p> <p>Methods</p> <p>In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection.</p> <p>Results</p> <p>We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection.</p> <p>Conclusions</p> <p>Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection.</p

Synergies between interstellar dust and heliospheric science with an Interstellar Probe

We discuss the synergies between heliospheric and dust science, the open science questions, the technological endeavors and programmatic aspects that are important to maintain or develop in the decade to come. In particular, we illustrate how we can use interstellar dust in the solar system as a tracer for the (dynamic) heliosphere properties, and emphasize the fairly unexplored, but potentially important science question of the role of cosmic dust in heliospheric and astrospheric physics. We show that an Interstellar Probe mission with a dedicated dust suite would bring unprecedented advances to interstellar dust research, and can also contribute-through measuring dust - to heliospheric science. This can, in particular, be done well if we work in synergy with other missions inside the solar system, thereby using multiple vantage points in space to measure the dust as it `rolls' into the heliosphere. Such synergies between missions inside the solar system and far out are crucial for disentangling the spatially and temporally varying dust flow. Finally, we highlight the relevant instrumentation and its suitability for contributing to finding answers to the research questions.Comment: 18 pages, 7 Figures, 5 Tables. Originally submitted as white paper for the National Academies Decadal Survey for Solar and Space Physics 2024-203

Independent Segregation of the H-2 Locus and the Locus for Responsiveness to Histamine-Sensitizing Factor

The inheritance of responsiveness to histamine-sensitizing factor of pertussis bacilli was examined in (SWR/J x CBA/J)F(1) x CBA/J backcross mice. We found that about half of the backcross mice inherited this responsiveness in both sexes. There was no linkage between the inheritance of responsiveness to histamine-sensitizing factor and the H-2(q) locus from the sensitive SW/J progenitor

Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals the immunologic facet of oncolytic therapy

<p>Abstract</p> <p>Background</p> <p>GLV-1h68 is an attenuated recombinant vaccinia virus (VACV) that selectively colonizes established human xenografts inducing their complete regression.</p> <p>Results</p> <p>Here, we explored xenograft/VACV/host interactions <it>in vivo </it>adopting organism-specific expression arrays and tumor cell/VACV <it>in vitro </it>comparing VACV replication patterns. There were no clear-cut differences <it>in vitro </it>among responding and non-responding tumors, however, tumor rejection was associated <it>in vivo </it>with activation of interferon-stimulated genes (ISGs) and innate immune host's effector functions (IEFs) correlating with VACV colonization of the xenografts. These signatures precisely reproduce those observed in humans during immune-mediated tissue-specific destruction (TSD) that causes tumor or allograft rejection, autoimmunity or clearance of pathogens. We recently defined these common pathways in the "immunologic constant of rejection" hypothesis (ICR).</p> <p>Conclusion</p> <p>This study provides the first prospective validation of a universal mechanism associated with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering a promising therapy of established cancers, may represent a reliable pre-clinical model to test therapeutic strategies aimed at modulating the central pathways leading to TSD; this information may lead to the identification of principles that could refine the treatment of cancer and chronic infection by immune stimulation or autoimmunity and allograft rejection through immune tolerance.</p

Long-term Efficacy, Safety, and Immunogenicity of Biosimilar Infliximab after One Year in a Prospective Nationwide Cohort

Background: It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort. Methods: A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Clinical remission, response, and biochemical response were evaluated at weeks 14, 30, and 54, respectively. Safety data were registered. Results: Three hundred fifty-three consecutive inflammatory bowel disease (209 CD and 144 UC) patients were included, of which 229 patients reached the week 54 endpoint at final evaluation. Age at disease onset: 24/28 years (median, interquartile range: 19-34/22-39) in patients with CD/UC. Forty-nine, 53, 48% and 86, 81 and 65% of patients with CD reached clinical remission and response by weeks 14, 30, and 54, respectively. Clinical remission and response rates were 56, 41, 43% and 74, 66, 50% in patients with UC. Clinical efficacy was influenced by previous anti-tumor necrosis factor (TNF) exposure in patients with a drug holiday beyond 1 year. The mean C-reactive protein level decreased significantly in both CD and UC by week 14 and was maintained throughout the 1-year follow-up (both UC/CD: P < 0.001). Thirty-one (8.8%) patients had infusion reactions and 32 (9%) patients had infections. Antidrug antibody positivity rates were significantly higher throughout patients with previous anti-TNF exposure; concomitant azathioprine prevented antidrug antibody formation in anti-TNF-naive patients with CD. Conclusions: Results from this prospective nationwide cohort confirm that CT-P13 is effective and safe in inducing and maintaining long-term remission in both CD and UC. Efficacy was influenced by previous anti-TNF exposure; no new safety signals were detected