Functional cardiac tissue engineering holds promise as a candidate therapy for myocardial infarction and heart failure. Generation of "strong-contracting and fast-conducting" cardiac tissue patches capable of electromechanical coupling with host myocardium could allow efficient improvement of heart function without increased arrhythmogenic risks. Towards that goal, we engineered highly functional 1 cm × 1 cm cardiac tissue patches made of neonatal rat ventricular cells which after 2 weeks of culture exhibited force of contraction of 18.0 ± 1.4 mN, conduction velocity (CV) of 32.3 ± 1.8 cm/s, and sustained chronic activation when paced at rates as high as 8.7 ± 0.8 Hz. Patches transduced with genetically-encoded calcium indicator (GCaMP6) were implanted onto adult rat ventricles and after 4-6 weeks assessed for action potential conduction and electrical integration by two-camera optical mapping of GCaMP6-reported Ca transients in the patch and RH237-reported action potentials in the recipient heart. Of the 13 implanted patches, 11 (85%) engrafted, maintained structural integrity, and conducted action potentials with average CVs and Ca transient durations comparable to those before implantation. Despite preserved graft electrical properties, no anterograde or retrograde conduction could be induced between the patch and host cardiomyocytes, indicating lack of electrical integration. Electrical properties of the underlying myocardium were not changed by the engrafted patch. From immunostaining analyses, implanted patches were highly vascularized and expressed abundant electromechanical junctions, but remained separated from the epicardium by a non-myocyte layer. In summary, our studies demonstrate generation of highly functional cardiac tissue patches that can robustly engraft on the epicardial surface, vascularize, and maintain electrical function, but do not couple with host tissue. The lack of graft-host electrical integration is therefore a critical obstacle to development of efficient tissue engineering therapies for heart repair.
Background and Aims: Traumatic pancreatic injury is associated with high morbidity and mortality rates, and the management strategies associated with the best clinical outcomes are unknown. Our aims were to identify the incidence of traumatic pancreatic injury in adult patients in the United States using the National Trauma Data Bank, evaluate management strategies and clinical outcomes, and identify predictors of in-hospital mortality. Materials and Methods: We retrospectively analyzed National Trauma Data Bank data from 2007 to 2011, and identified patients ⩾14 years old with pancreatic injuries either due to blunt or penetrating trauma. Patient characteristics, injury-associated factors, clinical outcomes, and in-hospital mortality rates were evaluated and compared between two groups stratified by injury type (blunt vs penetrating trauma). Statistical analyses used included Pearson’s chi-square, Fisher’s exact test, and analysis of variance. Factors independently associated with in-hospital mortality were identified using multivariable logistic regression. Results: We identified 8386 (0.3%) patients with pancreatic injuries. Of these, 3244 (38.7%) had penetrating injuries and 5142 (61.3%) had blunt injuries. Penetrating traumas were more likely to undergo surgical management compared with blunt traumas. The overall in-hospital mortality rate was 21.2% (n = 1776), with penetrating traumas more likely to be associated with mortality (26.5% penetrating vs 17.8% blunt, p < 0.001). Unadjusted mortality rates varied by management strategy, from 6.7% for those treated with a drainage procedure to >15% in those treated with pancreatic repair or resection. Adjusted analysis identified drainage procedure as an independent factor associated with decreased mortality. Independent predictors of mortality included age ⩾70 years, injury severity score ⩾15, Glasgow Coma Scale motor <6, gunshot wound, and associated injuries. Conclusions: Traumatic pancreatic injuries are a rare but critical condition. The incidence of pancreatic injury was 0.3%. The overall morbidity and mortality rates were 53% and 21.2%, respectively. Patients undergoing less invasive procedures, such as drainage, were associated with improved outcomes.
Surgical treatment of post-LVAD AI with aortic valve oversewing or leaflet repair or by bioprosthetic aortic valve replacement is effective at restoring functional capacity for CF LVAD patients who develop symptomatic, severe AI and can be performed safely with good results. Various transcatheter approaches to these difficult problems are also available and offer less invasive alternatives to conventional surgery.
the proportion of patients for whom an age-adjusted D-dimer threshold would have obviated the need for CPTA. There were 104 patients with a negative conventional D-dimer test and an RGS #10. In these patients, no PE was observed within 90 days (false-negative rate, 0%; 95% confidence interval [CI], 0%-2.8%). There were 273 patients with a negative ageadjusted D-dimer result and an RGS #10. Four of these patients were observed with PEs within 90 days (false-negative rate, 1.5%; 95% CI, 0.4%-3.7%). There was an 18.3% (95% CI, 15.9%-21.0%) absolute reduction in the proportion of patients aged >50 years who would merit CTPA by using age-adjusted D-dimer thresholds compared with a conventional D-dimer threshold.Comment: It seems there is a never ending series of papers of trying to limit imaging studies in patients with suspected venous thromboembolism. This paper, suggests a low 90-day failure rate to diagnose PE using the combination of adjusted D-dimer and pre-test clinical probability testing with the Geneva score. However, using an age-adjusted D-dimer threshold did result in missing more cases of PE then conventional D-dimer levels. Considering the false-negative rates for PE calculated among patients with negative age-adjusted D-dimer tests, along with PE identified upon presentation, the current observation suggests that use of age-adjusted D-dimer thresholds in combination with Revised Geneva Scores is likely safe. However, as the authors point out a prospective study design with adequate power for pre-specified subgroup analyses will be required to ensure safety of adopting an age-adjusted D-dimer threshold among older patients. Such a study will be necessary before use of ageadjusted D-dimer levels can be advocated in routine clinical care of patients with possible PE.
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