Objectives The aim of this study was to characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography ...(OCT). Background Plaque erosion and calcified nodule have not been systematically investigated in vivo. Methods A total of 126 patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or with a new set of diagnostic criteria for OCT. Results The incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest, compared with those with PR and OCT-CN (53.8 ± 13.1 years vs. 60.6 ± 11.5 years, 65.1 ± 5.0 years, p = 0.005). Compared with patients with PR, presentation with non–ST-segment elevation ACS was more common in patients with OCT-erosion (61.5% vs. 29.1%, p = 0.008) and OCT-CN (100% vs. 29.1%, p < 0.001). The OCT-erosion had a lower frequency of lipid plaque (43.6% vs. 100%, p < 0.001), thicker fibrous cap (169.3 ± 99.1 μm vs. 60.4 ± 16.6 μm, p < 0.001), and smaller lipid arc (202.8 ± 73.6° vs. 275.8 ± 60.4°, p < 0.001) than PR. The diameter stenosis was least severe in OCT-erosion, followed by OCT-CN and PR (55.4 ± 14.7% vs. 66.1 ± 13.5% vs. 68.8 ± 12.9%, p < 0.001). Conclusions Optical coherence tomography is a promising modality for identifying OCT-erosion and OCT-CN in vivo. The OCT-erosion is a frequent finding in patients with ACS, especially in those with non–ST-segment elevation ACS and younger patients. The OCT-CN is the least common etiology for ACS and is more common in older patients. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538 )
Summary Background Ixmyelocel-T is an expanded, multicellular therapy produced from a patient's own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ ...mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical, functional, symptomatic, and quality-of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy. We aimed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions. Methods In this randomised, double-blind, placebo-controlled phase 2B trial (ixCELL-DCM), patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy, who had left ventricular ejection fraction 35% or less, an automatic implantable cardioverter defibrillator, and who were ineligible for revascularisation procedures were randomly assigned (1:1) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months. Randomisation was done through an interactive (voice/web) response system. The pharmacist, treating physician, and coordinator at each site were unblinded, but the the follow-up team was completely blinded. The primary endpoint was a composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01670981. Findings Between April 2, 2013, and Jan 28, 2015, 126 participants were randomly assigned to receive either ixmyelocel-T (n=60) or placebo (n=66). 114 (90%) patients comprised the modified intention-to-treat population and 109 (87%) patients were included in the per-protocol primary efficacy analysis (58 in the ixmyelocel-T group and 51 in the placebo group). The primary efficacy endpoint was observed in 47 patients: 50 events in 25 (49%) of 51 patients in the placebo group and 38 events in 22 (38%) of 58 patients in the ixmyelocel-T group, which represents a 37% reduction in cardiac events compared with placebo (risk ratio 0·63 95% CI 0·42–0·97; p=0·0344). 41 (75%) of 51 participants in the placebo group had serious adverse events versus 31 (53%) of 58 in the ixmyelocel-T group (p=0·0197). Interpretation To the best of our knowledge, ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far. The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy resulted in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes. Funding Vericel Corporation.
Background. Retraction of problematic scientific articles after publication is one of the mechanisms for correcting the literature available to publishers. The market volume and the busi-ness model ...justify publishers’ ethical involvement in the post-publication quality control (PPQC) of human-health-related articles. The limited information about this subject led us to analyze Pub-Med-retracted articles and the main retraction reasons grouped by publisher. We propose a score to appraise publisher’s PPQC results. The dataset used for this article consists of 4844 Pub-Med-retracted papers published between 1.01.2009 and 31.12.2020. Methods. An SDTP score was constructed from the dataset. The calculation formula includes several parameters: speed (article exposure time (ET)), detection rate (percentage of articles whose retraction is initiated by the edi-tor/publisher/institution without the authors’ participation), transparency (percentage of retracted articles available online and the clarity of the retraction notes), and precision (mention of authors’ responsibility and percentage of retractions for reasons other than editorial errors). Results. The 4844 retracted articles were published in 1767 journals by 366 publishers, the average number of retracted articles/journal being 2.74. Forty-five publishers have more than 10 retracted articles, holding 88% of all papers and 79% of journals. Combining our data with data from another study shows that less than 7% of PubMed dataset journals retracted at least one article. Only 10.5% of the retraction notes included the individual responsibility of the authors. Nine of the top 11 publishers had the largest number of retracted articles in 2020. Retraction-reason analysis shows considerable differences between publishers concerning the articles’ ET: median values between 9 and 43 months (mistakes), 9 and 73 months (images), and 10 and 42 months (plagiarism and overlap). The SDTP score shows, from 2018 to 2020, an improvement in PPQC of four publishers in the top 11 and a decrease in the gap between 1st and 11th place. The group of the other 355 publishers also has a positive evolution of the SDTP score. Conclusions. Publishers have to get involved actively and measurably in the post-publication evaluation of scientific products. The introduction of reporting standards for retraction notes and replicable indicators for quantifying publishing QC can help increase the overall quality of scientific literature.
Coronary perforation is a potential complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We analyzed 2,097 CTO PCIs performed in 2,049 patients from 2012 to 2017. ...Patient age was 65 ± 10 years, 85% were men, and 36% had prior coronary artery bypass graft surgery. Technical and procedural success were 88% and 87%, respectively. A major periprocedural adverse cardiovascular event occurred in 2.6%. Coronary perforation occurred in 85 patients (4.1%); The frequency of Ellis class 1, 2, and 3 perforations was 21%, 26%, and 52%, respectively. Perforation occurred more frequently in older patients and those with previous coronary artery bypass graft surgery (61% vs 35%, p < 0.001). Cases with perforation were angiographically more complex (Multicenter CTO Registry in Japan score 3.0 ± 1.2 vs 2.5 ± 1.3, p < 0.001). Twelve patients (14%) with perforation experienced tamponade requiring pericardiocentesis. Patient age, previous PCI, right coronary artery target CTO, blunt or no stump, use of antegrade dissection re-entry, and the retrograde approach were associated with perforation. Adjusted odds ratio for periprocedural major periprocedural adverse cardiovascular events among patients with perforation was 15.04 (95% confidence interval 7.35 to 30.18). In conclusion, perforation occurs relatively infrequently in contemporary CTO PCI performed by experienced operators and is associated with baseline patient characteristics and angiographic complexity necessitating use of advanced crossing techniques. In most cases, perforations do not result in tamponade requiring pericardiocentesis, but they are associated with reduced technical and procedural success, higher periprocedural major adverse events, and reduced procedural efficiency.
Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. We investigated the potential of human mesenchymal stem cells (hMSCs) from ...adult bone marrow to undergo myogenic differentiation once transplanted into the adult murine myocardium.
A small bone marrow aspirate was taken from the iliac crest of healthy human volunteers, and hMSCs were isolated as previously described. The stem cells, labeled with lacZ, were injected into the left ventricle of CB17 SCID/beige adult mice. At 4 days after injection, none of the engrafted hMSCs expressed myogenic markers. A limited number of cells survived past 1 week and over time morphologically resembled the surrounding host cardiomyocytes. Immunohistochemistry revealed de novo expression of desmin, beta-myosin heavy chain, alpha-actinin, cardiac troponin T, and phospholamban at levels comparable to those of the host cardiomyocytes; sarcomeric organization of the contractile proteins was observed. In comparison, neither cardiac troponin T nor phospholamban was detected in the myotubes formed in vitro by MyoD-transduced hMSCs.
The purified hMSCs from adult bone marrow engrafted in the myocardium appeared to differentiate into cardiomyocytes. The persistence of the engrafted hMSCs and their in situ differentiation in the heart may represent the basis for using these adult stem cells for cellular cardiomyoplasty.
Optical coherence tomography (OCT) is a novel intravascular imaging modality with excellent spatial resolution. This study explored the utility of OCT in cardiac transplantation for the detection and ...characterization of early changes associated with coronary allograft vasculopathy (CAV).
Fifteen consecutive patients, 1 to 4 years after transplant with no angiographic evidence of CAV, underwent successful OCT imaging using the Fourier-domain OCT system (C7-XR, St. Jude Medical, St. Paul, MN) in the left anterior descending artery. Analysis included measurements of the lumen, intima, and media layers, and characterization of atherosclerotic plaques. Patients were stratified by intima-to-media (I/M) ratio and classified as normal (≤1) or abnormal (>1).
Patients were a mean of 2.8 years after transplant, 58 years old, and 92% were men. OCT imaging revealed 8 of 15 patients had intimal hyperplasia with an I/M ratio >1. Comparing those with I/M ratio of ≤1 and >1, the median (interquartile range) intimal thickness was greater (75 70-101 vs 206 97-269μm, p = 0.03), whereas the media thickness was no different (72 70-103 vs 94 73-113μm, p = 0.53). In addition, 7 of 15 patients had lipid-rich or calcified atherosclerotic plaques.
OCT provides high-resolution quantitative imaging of the coronary arteries and its use allows for detailed assessment of the coronary artery wall and early morphologic changes that occur after cardiac transplantation. The clinical predictive value of these OCT-derived measurements remains to be determined.
Background
Catheter-directed thrombolysis (CDL) is increasingly being used for the treatment of submassive and massive pulmonary embolism. Although this therapy has been shown to be effective at ...reducing right ventricle strain, the impact on clinical outcomes remains unclear. We therefore aimed to evaluate the outcomes of CDL compared to standard anticoagulation for submassive pulmonary embolism patients in a large cohort.
Methods
We conducted a retrospective observational study of consecutive patients with a primary diagnosis of submassive pulmonary embolism admitted to an intensive care unit within our health system between June 2014 and April 2016. We compared the outcome of patients treated with systemic anticoagulation (medical therapy) vs. catheter-based delivery of tissue plasminogen activator (tPA) (CDL). CDL patients were matched with medical therapy controls using a propensity-score matching algorithm based on the components of the simplified pulmonary embolism severity index (sPESI) score.
Results
Unadjusted mortality rates were 3.0% for CDL vs. 10.4% for medical therapy at 30 days and 8.1% for CDL vs. 22.9% for medical therapy at 1 year. In the propensity-score matched cohort, mortality rates were 3.1% for CDL vs. 6.1% for medical therapy at 30 days and 8.2% for CDL vs. 18.2% for medical therapy at 1 year. Length of stay was significantly shorter in the CDL group. The index admission bleeding and transfusion rates were not increased in the CDL group.
Conclusions
In patients presenting with acute submassive pulmonary embolism who are admitted to an intensive care unit, the group treated with CDL experienced reduced mortality at 30 days and 1 year when compared to medical therapy without increase in bleeding. Further randomized studies are required to confirm these findings.
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