Pediatric Cardiac Xenotransplantation: Recommendations for the Ethical Design of Clinical Trials

For children with complex congenital heart problems, cardiac allotransplantation is sometimes the best therapeutic option. However, availability of hearts for pediatric patients is limited, resulting in a long and growing waitlist, and a high mortality rate while waiting. Cardiac xenotransplantation has been proposed as one therapeutic alternative for neonates and infants, either in lieu of allotransplantation or as a bridge until an allograft becomes available. Scientific and clinical developments in xenotransplantation appear likely to permit cardiac xenotransplantation clinical trials in adults in the coming years. The ethical issues around xenotransplantation of the heart and other organs and tissues have recently been examined, but to date, only limited literature is available on the ethical issues that are attendant with pediatric heart xenotransplantation. Here, we summarize the ethical issues, focusing on (i) whether cardiac xenotransplantation should proceed in adults or children first, (ii) pediatric recipient selection for initial xenotransplantation trials, (iii) special problems regarding informed consent in this context, and (iv) related psychosocial and public perception considerations. We conclude with specific recommendations regarding ethically informed design of pediatric heart xenotransplantation trials

Outcomes after transplantation for “failed” Fontan: A single-institution experience

ObjectiveDespite the excellent outcomes in the current era after the Fontan procedure, it continues to have an inherent risk of failure. Cardiac transplantation provides 1 option for treating these patients; however, the indications for, timing of, and outcomes after, transplantation remain undefined. We examined our own institutional experience with transplantation for failed Fontan.MethodsThe records of 155 patients transplanted for congenital heart disease at a single institution from June 1984 to September 2007 were reviewed. Of these patients, 43 had undergone a previous Fontan procedure (25 male, 15 female; median age, 14.5 years; range, 1–47; 23 classic Fontan, 13 lateral tunnel, 4 extracardiac conduit, and 3 revised to shunt). The predictors of short- and long-term survival were evaluated, and the Fontan patients were compared with all other patients with congenital heart disease (n = 129, 78 male, 51 female).ResultsThe most common indications for transplantation included protein-losing enteropathy (PLE) (39.5%), chronic heart failure (41.8%), and acute post-Fontan failure (9.3%). The transplants performed in Fontan patients were more likely to require pulmonary artery reconstruction (85.4% vs 42.9%; P < .0001) and had longer cardiopulmonary bypass times (278 vs 179 minutes; P < .0001). The 90-day mortality rate was greater in the Fontan group (35.0% vs 20.0%; P = .055). No correlation was observed between the interval from Fontan to transplantation and morality; however, renal failure was a strong predictor of early mortality (odds ratio, 10.8; 95% confidence interval, 1.5–75.7).ConclusionsTransplantation is an acceptable treatment for patients with a failed Fontan. Clinical factors (instead of the indication for transplantation) appear to have the greatest correlation with early mortality

Posttransplant survival is not diminished in heart transplant recipients bridged with implantable left ventricular assist devices

BackgroundThe purpose of this study was to compare posttransplantation morbidity and mortality in orthotopic heart transplant recipients bridged to transplant with a left ventricular assist device with nonbridged recipients. To account for potential differences across device types, we stratified bridge-to-transplant recipients by type of ventricular assist device: extracorporeal (EXTRA), paracorporeal (PARA), and intracorporeal (INTRA).MethodsThe United Network for Organ Sharing provided de-identified patient-level data. The study population included 10,668 orthotopic heart transplant recipients aged 18 years old or older and undergoing transplantation between January 1, 2001, and December 31, 2006. Follow-up data were provided through August 3, 2008, with a mean follow-up time of 3.17 ± 2.15 years (range, 0–8.11 years). The primary outcome was actuarial posttransplant graft survival. Other outcomes of interest included infection, stroke, and dialysis during the transplant hospitalization; primary graft failure at 30 days; transplant hospitalization length of stay; and long-term complications including diabetes mellitus, transplant coronary artery disease, and chronic dialysis. Multivariable Cox proportional hazards regression (backward, P < .15) was used to determine the relationship between groups and overall graft survival, and multivariable logistic regression analysis (backward, P < .15) was used to determine the relationship between groups and secondary outcome measures.ResultsIn multivariable Cox regression analysis, when compared with the nonbridged group, risk-adjusted greater than 90-day graft survival was diminished among the EXTRA group (hazard ratio = 3.54, 2.28–5.51, P < .001), but not the INTRA group (1.04, 0.719–1.51, P = .834) or the PARA group (1.06, 0.642–1.76, P = .809). There were no significant differences in risk-adjusted graft survival across the 4 groups during the 90-days to 1-year or 1- to 5-year intervals. However, at more than 5 years, risk-adjusted graft survival in the INTRA group (0.389, 0.205–0.738, P = .004) was better than in the nonbridged group. The EXTRA, PARA, and INTRA groups all experienced increased risks of infection. The EXTRA group had increased risks of dialysis, stroke, and primary graft failure at 30 days, whereas neither the PARA nor the INTRA group differed from the nonbridged group. Long-term complications did not differ by group.ConclusionThe use of implantable left ventricular assist devices as bridges to transplantation, including both intracorporeal and paracorporeal devices, is not associated with diminished posttransplant survival. However, 90-day survival was diminished in recipients bridged with extracorporeal devices

Del Nido Cardioplegia can be safely administered in high-risk coronary artery bypass grafting surgery after acute myocardial infarction: a propensity matched comparison

Del Nido (DN) cardioplegia solution provides a depolarized hyperkalemic arrest lasting up to 60 minutes, and the addition of lidocaine may limit intracellular calcium influx. Single-dose DN cardioplegia solution may offer an alternative myocardial protection strategy to multi-dose cold whole blood (WB) cardioplegia following acute myocardial infarction (AMI). We retrospectively reviewed 88 consecutive patients with AMI undergoing coronary artery bypass (CABG) surgery with cardioplegic arrest between June 2010 to June 2012. Patients exclusively received WB (n = 40, June 2010-July 2011) or DN (n = 48, August 2011-June 2012) cardioplegia. Preoperative and postoperative data were retrospectively reviewed and compared using propensity scoring. No significant difference in age, maximum preoperative serum troponin level, ejection fraction, and STS score was present between DN and WB. A single cardioplegia dose was given in 41 DN vs. 0 WB patients (p < 0.001), and retrograde cardioplegia was used 10 DN vs. 31 WB patients (p < 0.001). Mean cardiopulmonary bypass and cross clamp times were significantly shorter in the DN group versus WB group. Tranfusion rate, length of stay, intra-aortic balloon pump requirement, post-operative inotropic support, and 30-day mortality was no different between groups. One patient in the WB group required a mechanical support due to profound cardiogenic shock. DN cardioplegia may provide equivalent myocardial protection to existing cardioplegia without negative inotropic effects in the setting of acute myocardial infarction

Readjusting Our Sporting Sites/Sight: Sportification and the Theatricality of Social Life

This paper points out the potential of using sport for the analysis of society. Cultivated human movement is a specific social and cultural subsystem (involving sport, movement culture and physical culture), yet it becomes a part of wider social discourses by extending some of its characteristics into various other spheres. This process, theorised as sportification, provides as useful concept to examine the permeation of certain phenomena from the area of sport into the social reality outside of sport. In this paper, we investigate the phenomena of sportification which we parallel with visual culture and spectatorship practices in the Renaissance era. The emphasis in our investigation is on theatricality and performativity; particularly, the superficial spectator engagement with modern sport and sporting spectacles. Unlike the significance afforded to visualisation and deeper symbolic interpretation in Renaissance art, contemporary cultural shifts have changed and challenged the ways in which the active and interacting body is positioned, politicised, symbolised and ultimately understood. We suggest here that the ways in which we view sport and sporting bodies within a (post)modern context (particularly with the confounding amalgamations of signs and symbols and emphasis on hyper-realities) has invariably become detached from sports' profound metaphysical meanings and resonance. Subsequently, by emphasising the associations between social theatrics and the sporting complex, this paper aims to remind readers of ways that sport—as a nuanced phenomenon—can be operationalised to help us to contemplate questions about nature, society, ourselves and the complex worlds in which we live

Is isolated aortic valve replacement sufficient to treat concomitant moderate functional mitral regurgitation? A propensity-matched analysis

Abstract Background A significant proportion of patients presenting for isolated aortic valve replacement (AVR) demonstrate some degree of functional mitral regurgitation (fMR). Guidelines addressing concomitant mitral valve intervention in those patients with moderate fMR lack strong evidence-based support. Our aim is to determine the effect of untreated moderate fMR at the time of AVR on long-term survival. Methods All patients undergoing isolated AVR from 2000 to 2013 at our institution were retrospectively reviewed. Patients were stratified according to severity of preoperative fMR; 0–1+ MR (Group NoMR, n = 1826) and 2–3+ MR (Group MR, n = 330). All patients in Group MR were propensity-matched with patients in Group NoMR to control for differences in baseline characteristics. The primary outcome of interest was overall survival. Results Propensity analysis matched 330 patients from each group. Mean age was 77.9 ± 10.0 years and 50.6% were male. There were no differences in baseline demographics, echocardiographic parameters, or co-morbidities between groups. Kaplan-Meier analysis showed significantly worse medium and long-term survival in Group MR compared to Group NoMR (log-rank p = 0.02). Follow-up echocardiography showed slightly more severe MR in Group MR (1.1 ± 0.7 MR vs. 0.8 ± 0.7 NoMR, p = 0.03) at 1 year. Conclusions Patients undergoing isolated AVR with concomitant 2–3+ fMR experience poorer long-term survival than those patients with no or mild fMR. This suggests that mitral valve intervention may be necessary in patients undergoing AVR with clinically significant fMR

The prevalence of hyperglycemia and its association with perioperative outcomes in gynecologic surgery: a retrospective cohort study

Abstract Background Preoperative hyperglycemia has been associated with perioperative morbidity in general surgery patients. Additionally, preoperative hyperglycemia may indicate underlying impaired glucose metabolism. Thus, identification of preoperative hyperglycemia may provide an opportunity to mitigate both short-term surgical and long-term health risk. We aimed to study this phenomenon specifically in the gynecologic surgery population. Specifically, we aimed to evaluate the association between preoperative hyperglycemia and perioperative complications in gynecologic surgery patients and to characterize adherence to diabetes screening guidelines. Methods This retrospective cohort study included 913 women undergoing major gynecologic surgery on an enhanced recovery pathway from January 2018 to July 2019. The main exposure was day of surgery glucose ≥ 140 g/dL. Multivariate regression identified risk factors for hyperglycemia and composite and wound-specific complications. Results Sixty-seven (7.3%) patients were hyperglycemic. Diabetes (aOR 24.0, 95% CI 12.3–46.9, P < .001) and malignancy (aOR 2.3, 95% CI 1.2–4.5, P = .01) were associated with hyperglycemia. Hyperglycemia was not associated with increased odds of composite perioperative (aOR 1.3, 95% CI 0.7–2.4, P = 0.49) or wound-specific complications (aOR 1.1, 95% CI 0.7–1.5, P = 0.76). Of nondiabetic patients, 391/779 (50%) met the USPSTF criteria for diabetes screening; 117 (30%) had documented screening in the preceding 3 years. Of the 274 unscreened patients, 94 (34%) had day of surgery glucose levels suggestive of impaired glucose metabolism (glucose ≥ 100 g/dL). Conclusion In our study cohort, the prevalence of hyperglycemia was low and was not associated with higher risk of composite or wound-specific complications. However, adherence to diabetes screening guidelines was poor. Future studies should aim to develop a preoperative blood glucose testing strategy that balances the low utility of universal glucose screening with the benefit of diagnosing impaired glucose metabolism in at-risk individuals