Quantifying the immune response to a tissue-engineered porcine extracellular matrix.

Aim: Structural valvular deterioration of xenogenic heart valve replacements is thought to be due to a chronic immune response. We sought to engineer porcine extracellular matrix that elicits minimal inflammatory immune response. Materials & methods: Whole blood, bone marrow and pericardium were collected from patients undergoing elective cardiac surgery. Porcine extracellular matrix was decellularized, reseeded with homologous mesenchymal stem cells and exposed to whole blood. Results: DAPI stain confirmed the absence of cells after decellularization, and presence of mesenchymal stem cells after recellularization. There was a significant reduction in IL-1ß and TNF-α production in the recellularized matrix. Conclusion: Recellularization of porcine matrix is successful at attenuating the xenogenic immune response and may provide a suitable scaffold to address the current limitations of prosthetic heart valve replacements.

Deterioration of tissue heart valve replacements is thought to be due to a chronic immune response. We sought to remove cells from a pig derived tissue and replace those cells with human stem cells to create a scaffold that results in a reduced immune response. Whole blood, bone marrow and pericardium were collected from patients undergoing elective cardiac surgery. The pig derived tissue had the cells removed, were replaced with human stem cells and exposed to whole blood. Tissue stain confirmed the absence of cells after removal, and presence of stem cells after replacement of cells. There was a significant reduction in markers of immune response in the recellularized tissue. Removal of cells from pig derived tissue and replacement with human stem cells is successful at reducing the immune response to animal tissue and may provide a suitable scaffold to address the current limitations of heart valve replacement options.

A systematic review and meta-analysis of coronary artery disease and revascularization in lung transplant patients.

Coronary artery disease (CAD) is common in candidates for lung transplantation (LTx) and has historically been considered a relative contraindication to transplantation. We look to review the outcomes of LTx in patients with CAD and determine the optimum revascularization strategy in LTx candidates. PubMed, Medline and Web of Science were systematically searched by three authors for articles comparing the outcomes of LTx in patients with CAD and receiving coronary revascularization. In total 1668 articles were screened and 12 were included in this review.Preexisting CAD in LTx recipients was not associated with significantly increased postoperative morbidity or mortality. The pooled estimates of mortality rate at 1, 3 and 5 years indicated significantly inferior survival in LTx recipients with a prior history of coronary artery bypass grafting (CABG) [odds ratio (OR), 1.84; 95% confidence interval (CI), 1.53-2.22; P < 0.00001; I2 = 0%; OR, 1.52; 95% CI, 1.21-1.91; P = 0.0003; I2 = 0%; OR, 1.62; 95% CI, 1.13-2.33; P = 0.008; I2 = 71%, respectively). However, contemporary literature suggests that survival rates in LTx recipients with CAD that received revascularization either by percutaneous coronary intervention (PCI), previous or concomitant CABG, are similar to patients who did not receive revascularization. Trends in postoperative morbidity favored CABG in the rates of myocardial infarction and repeat revascularization, whereas rates of stroke favored PCI. The composite results of this study support the consideration of patients with CAD or previous coronary revascularization for LTx. Prospective, randomized controlled trials with consistent patient populations and outcomes reporting are required to fully elucidate the optimum revascularization strategy in LTx candidates.

Coronary Artery Revascularization in Heart Transplant Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the primary cause of late mortality after heart transplantation. We look to provide a comprehensive review of contemporary revascularization strategies in CAV. METHODS: PubMed and Web of Science were systematically searched by 3 authors. 1,870 articles were initially screened and 24 were included in this review. RESULTS: PCI is the main revascularization technique utilized in CAV. The pooled estimates for restenosis significantly favored DES over BMS (OR 4.26; 95% CI: 2.54-7.13; p < 0.00001; I2 = 4%). There were insufficient data to quantitatively compare mortality following DES versus BMS. There was no difference in short-term mortality between CABG and PCI. In-hospital mortality was 0.0% for CABG and ranged from 0.0 to 8.34% for PCI. One-year mortality was 8.0% for CABG and 5.0-25.0% for PCI. CABG had a potential advantage at 5 years. Five-year mortality was 17.0% for CABG and ranged from 14 to 40.4% following PCI. Select measures of postoperative morbidity trended toward superior outcomes for CABG. CONCLUSION: In CAV, PCI is the primary revascularization strategy utilized, with DES exhibiting superiority to BMS regarding postoperative morbidity. Further investigation into outcomes following CABG in CAV is required to conclusively elucidate the superior management strategy in CAV.

Recellularization of xenograft heart valves reduces the xenoreactive immune response in an in vivo rat model.

OBJECTIVES: Our aim was to address the role of autologous mesenchymal stem cell recellularization of xenogenic valves on the activation of the xenoreactive immune response in an in vivo rat model. METHODS: Explanted aortic valve constructs from female Hartley guinea pigs were procured and decellularized, followed by recellularization with autologous Sprague-Dawley rat mesenchymal stem cells. Aortic valve xenografts were then implanted into the infrarenal aorta of recipient rats. Grafts were implanted as either autologous grafts, non-decellularized (NGP), decellularized and recellularized xenografts (RGP). Rats were euthanized after 7 and 21 days and exsanguinated and the grafts were explanted. RESULTS: The NGP grafts demonstrated significant burden of granulocytes (14.3 cells/HPF) and CD3+ T cells (3.9 cells/HPF) compared to the autologous grafts (2.1 granulocytes/HPF and 0.72 CD3+ T cells/HPF) after 7 days. A lower absolute number of infiltrating granulocytes (NGP vs autologous, 6.4 vs 2.4 cells/HPF) and CD3+ T cells (NGP vs autologous, 2.8 vs 0.8 cells/HPF) was seen after 21 days. Equivalent granulocyte cell infiltration in the RGP grafts (2.4 cells/HPF) compared to the autologous grafts (2.1 cells/HPF) after 7 and 21 days (2.8 vs 2.4 cells/HPF) was observed. Equivalent CD3+ T-cell infiltration in the RGP grafts (0.63 cells/HPF) compared to the autologous grafts (0.72 cells/HPF) after 7 and 21 days (0.7 vs 0.8 cells/HPF) was observed. Immunoglobulin production was significantly greater in the NGP grafts compared to the autologous grafts at 7 (123.3 vs 52.7 mg/mL) and 21 days (93.3 vs 71.6 mg/mL), with a similar decreasing trend in absolute production. Equivalent immunoglobulin production was observed in the RGP grafts compared to the autologous grafts at 7 (40.8 vs 52.7 mg/mL) and 21 days (29.5 vs 71.6 mg/mL). CONCLUSIONS: Autologous mesenchymal stem cell recellularization of xenogenic valves reduces the xenoreactive immune response in an in vivo rat model and may be an effective approach to decrease the progression of xenograft valve dysfunction.

Progressive Dyspnea With Recurrent Pneumothoraces.

CASE PRESENTATION: A 34-year-old previously healthy man of Korean descent (height, 174 cm; weight, 47.4 kg) demonstrated dyspnea with cough and chest tightness. The patient had no relevant occupational exposures and no history of illicit drug or tobacco use. His medical history was notable for chronic sinus tachycardia of undetermined cause, hypertension, gout, glaucoma of the right eye, and a remote history of an intracranial malignancy 24 years prior treated with unspecified chemotherapy, craniotomy, and ventriculoperitoneal shunt placement. His active medications included diltiazem, candesartan, and colchicine as needed.

The Impact of Preoperative Frailty on the Clinical and Cost Outcomes of Adult Cardiac Surgery in Alberta, Canada: A Cohort Study.

BACKGROUND: There is limited information about the impact of frailty on public payer costs in cardiac surgery. This study aimed to determine quality-adjusted life-years (QALYs) and costs associated with preoperative frailty in patients referred for cardiac surgery. METHODS: We retrospectively compared costs of frailty in a cohort of 529 patients aged ≥ 50 years who were referred for nonemergent cardiac surgery in Alberta. Patients were screened preoperatively for frailty, defined as a score of 5 or greater on the Clinical Frailty Scale. The primary outcome measure was public payer costs attributable to frailty, calculated in a difference-in-difference (DID) model. RESULTS: The prevalence of frailty was 10% (n = 51; 95% confidence interval [CI], 7%-12%). Median (interquartile range) costs for frail patients were higher in the first year postsurgery ($200,709 [$146,177-$486,852] vs $147,730 [$100,674-$177,025]; P < 0.001) compared to nonfrail; the difference-in-difference attributable cost of frailty was $57,836 (95% CI, $-28,608-$144,280). At 1 year, frail patients had fewer QALYs realized compared to nonfrail patients (0.71 [0.57-0.77] vs 0.82 [0.75-0.86], P < 0.001), whereas QALYs gained were similar (0.02 [-0.02-0.05] vs 0.02 [0.00-0.04], P = 0.58, median difference 0.003 [95% CI, -0.01-0.02]) in frail and nonfrail patients. CONCLUSIONS: Frailty screening identified a population with greater impairment in quality-of-life and greater healthcare costs. Costs attributable to frailty represent opportunity costs that should be considered in future cardiac surgical services planning in the context of our aging population and the growing prevalence of frailty.

CONTEXTE: Il existe peu de renseignements concernant les répercussions de la fragilité sur les coûts pour les payeurs publics en chirurgie cardiaque. Cette étude visait à déterminer les années de vie pondérées par la qualité (QALY, pour Quality-Adjusted Life-Years) et les coûts associés à la fragilité préopératoire chez les patients dirigés vers un service de chirurgie cardiaque. MÉTHODOLOGIE: Nous avons comparé de façon rétrospective les coûts de la fragilité dans une cohorte de 529 patients âgés de 50 ans ou plus qui ont été dirigés vers un service de chirurgie cardiaque pour une intervention non urgente en Alberta. Un dépistage de la fragilité, définie comme un score de 5 ou plus à l'échelle CFS (Clinical Frailty Scale), a été effectué avant l'intervention. Le principal critère d'évaluation était le coût attribuable à la fragilité pour les payeurs publics, calculé selon un modèle d'écart des différences. RÉSULTATS: La prévalence de la fragilité a été de 10 % (n = 51; intervalle de confiance [IC] à 95 % : 7 à 12 %). Les coûts médians (écart interquartile) dans la première année suivant l'intervention chirurgicale ont été plus élevés chez les patients fragiles que chez les patients non fragiles (200 709 $ [146 177 $ à 486 852 $] contre 147 730 $ [100 674 $ à 177 025 $]; p < 0,001); le coût attribuable de la fragilité selon le modèle d'écart des différences a été de 57 836 $ (IC à 95 % : −28 608 $ à 144 280 $). À 1 an, les patients fragiles avaient moins de QALY réalisées que les patients non fragiles (0,71 [0,57 à 0,77] contre 0,82 [0,75 à 0,86]; p < 0,001), alors que le nombre de QALY gagnées était similaire (0,02 [−0,02 à 0,05] contre 0,02 [0,00 à 0,04]; p = 0,58; différence médiane : 0,003 [IC à 95 % : −0,01 à 0,02]) chez les patients fragiles et non fragiles. CONCLUSIONS: Le dépistage de la fragilité a permis de repérer une population associée à une perte plus importante de qualité de vie et à des coûts plus élevés en soins de santé. Les coûts attribuables à la fragilité représentent des coûts de renonciation qui doivent être considérés dans la planification future des services de chirurgie cardiaque, dans le contexte du vieillissement de notre population et de la prévalence croissante de fragilité.

Role of preoperative intravenous iron therapy to correct anemia before major surgery: a systematic review and meta-analysis.

BACKGROUND: Preoperative anemia is a common comorbidity that often necessitates allogeneic blood transfusion (ABT). As there is a risk associated with blood transfusions, preoperative intravenous iron (IV) has been proposed to increase the hemoglobin to reduce perioperative transfusion; however, randomized controlled trials (RCT) investigating this efficacy for IV iron are small, limited, and inconclusive. Consequently, a meta-analysis that pools these studies may provide new and clinically useful information. METHODS/DESIGN: Databases of MEDLINE, EMBASE, EBM Reviews; Cochrane-controlled trial registry; Scopus; registries of health technology assessment and clinical trials; Web of Science; ProQuest Dissertations and Theses; Clinicaltrials.gov; and Conference Proceedings Citation Index-Science (CPCI-S) were searched. Also, we screened all the retrieved reference lists. SELECTION CRITERIA: Titles and abstracts were screened for relevance (i.e., relevant, irrelevant, or potentially relevant). Then, we screened full texts of those citations identified as potentially applicable. RESULTS: Our search found 3195 citations and ten RCTs (1039 participants) that met our inclusion criteria. Preoperative IV iron supplementation significantly decreases ABT by 16% (risk ratio (RR): 0.84, 95% confidence interval [CI]: 0.71, 0.99, p = 0.04). In addition, preoperatively, hemoglobin levels increased after receiving IV iron (mean difference [MD] between the study groups: 7.15 g/L, 95% CI: 2.26, 12.04 g/L, p = 0.004) and at follow-up > 4 weeks postoperatively (MD: 6.46 g/L, 95% CI: 3.10, 9.81, p = 0.0002). Iron injection was not associated with increased incidence of non-serious or serious adverse effects across groups (RR: 1.13, 95% CI: 0.78, 1.65, p = 0.52) and (RR: 0.96, 95% CI: 0.44, 2.10, p = 0.92) respectively. CONCLUSIONS: With moderate certainty, due to the high risk of bias in some studies in one or two domains, we found intravenous iron supplementation is associated with a significant decrease in the blood transfusions rate, and modest hemoglobin concentrations rise when injected pre-surgery compared with placebo or oral iron supplementation. However, further full-scale randomized controlled trials with robust methodology are required. In particular, the safety, quality of life, and cost-effectiveness of different intravenous iron preparations require further evaluation.

Costs and consequences of acute kidney injury after cardiac surgery: A cohort study.

OBJECTIVES: Acute kidney injury (AKI) is common after cardiac surgery. We quantified the mortality and costs of varying degrees of AKI using a population-based cohort in Alberta, Canada. METHODS: A cohort of patients undergoing cardiac surgery from 2004 to 2009 was assembled from linked Alberta administrative databases. AKI was classified by Kidney Disease Improving Global Outcomes stages of severity. Our outcomes were in-hospital mortality, length of stay, and costs; among survivors, we also examined mortality and costs at 365 days. Estimates were adjusted for demographic characteristics, comorbidities, and other covariates. RESULTS: Ten thousand one hundred seventy participants were included, of whom 9771 patients were discharged to community. Overall in-hospital mortality, costs, and length of stay were 4%, 7 days, and Can $34,000, respectively. Postcardiac surgery, AKI occurred in 25%. Compared with those without AKI, AKI was independently associated with increased in-hospital mortality across severity categories, with the highest risk (adjusted odds ratio, 37.1; 95% confidence interval, 26.3-52.1; P < .001) in patients who required acute dialysis. AKI severity was associated with increased hospital days and costs, with costs ranging from 1.21 for stage 1 AKI (95% confidence interval, 1.17-1.23) to 2.74 for acute dialysis (95% confidence interval, 2.49-3.00) (P < .001) times higher than in patients without AKI, after covariate adjustment. Postdischarge to 365 days, patients with AKI continued to experience increased costs up to 1.35-fold, and patients who required dialysis acutely continued to experience a 2.86-fold increased mortality. CONCLUSIONS: AKI remains an important indicator of mortality and health care costs postcardiac surgery.

Association between levosimendan, postoperative AKI, and mortality in cardiac surgery: Insights from the LEVO-CTS trial.

OBJECTIVES: We aimed to evaluate the association between levosimendan treatment and acute kidney injury (AKI) as well as assess the clinical sequelae of AKI in cardiac surgery patients with depressed left ventricular function (ejection fraction <35%). METHODS: Patients in the LEVO-CTS trial undergoing on-pump coronary artery bypass grafting (CABG), valve, or CABG/valve surgery were stratified by occurrence and severity of postoperative AKI using the AKIN classification. The association between levosimendan infusion and AKI was modeled using multivariable regression. RESULTS: Among 854 LEVO-CTS patients, 231 (27.0%) experienced postoperative AKI, including 182 (21.3%) with stage 1, 35 (4.1%) with stage 2, and 14 (1.6%) with stage 3 AKI. The rate of AKI was similar between patients receiving levosimendan or placebo. The odds of 30-day mortality significantly increased by AKI stage compared to those without AKI (stage 1: adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI] 0.8-4.9; stage 2: aOR 9.1, 95% CI 3.2-25.7; stage 3: aOR 12.4, 95% CI 3.0-50.4). No association was observed between levosimendan, AKI stage, and odds of 30-day mortality (interaction P = .69). Factors independently associated with AKI included increasing age, body mass index, diabetes, and increasing baseline systolic blood pressure. Increasing baseline eGFR and aldosterone antagonist use were associated with a lower risk of AKI. CONCLUSIONS: Postoperative AKI is common among high-risk patients undergoing cardiac surgery and associated with significantly increased risk of 30-day death or dialysis. Levosimendan was not associated with the risk of AKI.

SUPERIOR SVG: no touch saphenous harvesting to improve patency following coronary bypass grafting (a multi-Centre randomized control trial, NCT01047449).

BACKGROUND: Single centre studies support No Touch (NT) saphenous vein graft (SVG) harvesting technique. The primary objective of the SUPERIOR SVG study was to determine whether NT versus conventional (CON) SVG harvesting was associated with improved SVG patency 1 year after coronary artery bypass grafting surgery (CABG). METHODS: Adults undergoing isolated CABG with at least 1 SVG were eligible. CT angiography was performed 1-year post CABG. Leg adverse events were assessed with a questionnaire. A systematic review was performed for published NT graft patency studies and results aggregated including the SUPERIOR study results. RESULTS: Two hundred and-fifty patients were randomized across 12-centres (NT 127 versus CON 123 patients). The primary outcome (study SVG occlusion or cardiovascular (CV) death) was not significantly different in NT versus CON (NT: 7/127 (5.5%), CON 13/123 (10.6%), p = 0.15). Similarly, the proportion of study SVGs with significant stenosis or total occlusion was not significantly different between groups (NT: 8/102 (7.8%), CON: 16/107 (15.0%), p = 0.11). Vein harvest site infection was more common in the NT patients 1 month postoperatively (23.3% vs 9.5%, p < 0.01). Including this study's results, in a meta-analysis, NT was associated with a significant reduction in SVG occlusion, Odds Ratio 0.49, 95% Confidence Interval 0.29-0.82, p = 0.007 in 3 randomized and 1 observational study at 1 year postoperatively. CONCLUSIONS: The NT technique was not associated with improved patency of SVGs at 1-year following CABG while early vein harvest infection was increased. The aggregated data is supportive of an important reduction of SVG occlusion at 1 year with NT harvesting. TRIAL REGISTRATION: NCT01047449 .

Prevalence and Correlates of Psychiatric Symptoms in Minimally Verbal Children and Adolescents With ASD.

Despite many studies documenting the prevalence of various co-occurring psychiatric symptoms in children and adults with ASD, less is known about how these symptoms relate to subtypes defined by particular phenotypic features within the ASD population. We examined the severity and prevalence of comorbid symptoms of psychopathology, emotion dysregulation, and maladaptive behaviors, as well as adaptive functioning, in a group of 65 minimally verbal children (n = 33) and adolescents (n = 32) with ASD. On the Child and Adolescent Symptom Inventory (CASI-5), for all the symptom classifications except oppositional defiant disorder and conduct disorder, more participants in our sample showed elevated or clinically concerning severity scores relative to the general population. On the Emotion Dysregulation Inventory (EDI), the mean scores for Reactivity and Dysphoria factors in our sample were lower than in the autism calibration sample, which included a large number of inpatient youth with ASD. Overall, few differences were found between the children and adolescents within this severely impaired group of ASD individuals based on clinical cutoff scores on the CASI-5 and EDI factor scores. Psychiatric comorbidities and emotion dysregulation measures were not correlated with autism symptom severity or with measures of adaptive functioning, and were largely unrelated to IQ in our sample. The number of clinically significant psychiatric symptoms on the CASI-5 emerged as the main predictor of maladaptive behaviors. Findings suggest a wide range of co-occurring psychopathology and high degree of maladaptive behavior among minimally verbal children and adolescents with ASD, which are not directly attributable to autism symptom severity, intellectual disability or limitations in adaptive functioning.

Therapeutic hypothermia as an adjunct to extracorporeal membrane oxygenation for acute respiratory distress and refractory hypoxemia.

Legionella community-acquired pneumonia necessitating veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome has been reported in adults. However, few options remain in cases of refractory hypoxemia on veno-venous extracorporeal membrane oxygenation. Herein, we describe adjunctive extended therapeutic hypothermia for refractory hypoxemia despite veno-venous extracorporeal membrane oxygenation for successful management of severe acute respiratory distress syndrome secondary to Legionella.

Variables Associated With Cardiac Surgical Waitlist Mortality From a Population-Based Cohort.

BACKGROUND: Cardiac surgery waitlist recommendations, which were developed based on expert opinion, poorly predict preoperative mortality. Studies reporting risk factors for waitlist mortality have not evaluated the risks including nonadherence to waitlist benchmarks. METHODS: In patients who underwent cardiac surgery or died on the waitlist between 2005 and 2015, we used a Fine and Gray competing risk model to identify independent predictors of waitlist mortality in 12,106 patients scheduled for urgent, semiurgent, or nonurgent surgery. The predictive variables were compared with Canadian Cardiovascular Society (CCS) waitlist recommendations using the Akaike information criterion. RESULTS: A total of 101 (0.8%) patients died awaiting surgery. The median wait times and frequency waitlist deaths among emergent, urgent, semi-urgent, and nonurgent surgery were 0.6, 7.4, 69.0, 55.5 days (P < 0.001) and 6.3%, 0.8%, 0.3%, 0.6% (P < 0.001), respectively. Adherence to CCS waitlist recommendations was higher in patients who died on the waitlist (51.6% vs 70.8%, P = 0.001) and was not predictive of waitlist mortality (hazard ratio 1.48, 95% confidence interval 0.62-0.56). Independent predictors of waitlist mortality were age, aortic surgery, ejection fraction < 35%, urgent surgery, prior myocardial infarction, haemodynamic instability during cardiac catheterization, hypertension, and dyslipidemia. These variables were superior to current CCS guidelines (Akaike information criterion 1251 vs 1317, likelihood ratio test P < 0.001). CONCLUSIONS: CCS waitlist recommendations were poorly predictive of waitlist mortality and the majority of waitlist deaths occur within recommended benchmarks. We identified variables associated with waitlist mortality with improved clinical performance. Our findings suggest a need to re-evaluate cardiac surgical triage criteria using evidence-based data.

An experimental study of word learning in minimally verbal children and adolescents with autism spectrum disorder.

BACKGROUND AND AIMS: When children hear a novel word, they tend to associate it with a novel rather than a familiar object. The ability to map a novel word to its corresponding referent is thought to depend, at least in part, on language-learning strategies, such as mutual exclusivity and lexical contrast. Although the importance of word learning strategies has been broadly investigated in typically developing children as well as younger children with autism spectrum disorder, who are usually language delayed, there is a paucity of research on such strategies and their role in language learning in school-age children and adolescents with autism spectrum disorder who have failed to develop fluent speech. In this study, we examined the ability of minimally verbal children and adolescents with autism spectrum disorder to learn and retain novel words in an experimental task, as well as the cognitive, language, and social correlates of these abilities. We were primarily interested in the characteristics that differentiated between three subgroups of participants: those unable to use word learning strategies, particularly mutual exclusivity, to learn novel words; those able to learn novel words over several exposure trials but not able retain them; and those able to retain the words they learned. METHODS: Participants were 29 minimally verbal individuals with autism spectrum disorder from 5 to 17 years of age. Participants completed a computerized touchscreen novel-word-learning procedure followed by assessments of immediate retention and of delayed retention, two hours later. Participants were grouped according to whether they passed/failed at least 7 of 8 (binomial p<.035) novel word learning trials and 7 of 8 immediate or delayed retention trials, and were compared on measures of nonverbal IQ, receptive and expressive vocabulary, phonological processing, joint attention and symptom severity. RESULTS: Of 29 participants, 14 failed both learning and immediate retention, 8 passed learning but failed immediate retention, and 7 passed both learning and immediate retention. Group performance was highly similar for delayed retention. Language level, particularly expressive vocabulary, differentiated between participants who did and did not succeed in retention, even while controlling for differences in nonverbal IQ. CONCLUSIONS: The ability of minimally verbal school-age children and adolescents with autism spectrum disorder to identify the referents of novel words was associated with nonverbal cognitive abilities. Retention of words was associated with concurrent expressive language abilities. IMPLICATIONS: Our findings of associations between the retention of novel words acquired in a lab-based experimental task and concurrent language ability warrants further investigation with larger samples and longitudinal research designs, which may support the incorporation of contrastive word learning strategies into language learning interventions for severely language-impaired individuals with autism spectrum disorder.

Transcatheter Mitral Valve Intervention for Chronic Mitral Regurgitation: A Plethora of Different Technologies.

Chronic mitral regurgitation (MR) remains a common cardiovascular condition resulting in significant morbidity and mortality. With an aging population, increasing trends for both primary (degenerative) and secondary (functional) MR have become apparent. Although the gold standard remains surgical intervention with mitral valve repair/replacement, comorbid conditions have steered the development of less invasive technologies to mitigate perioperative surgical risk. Transcatheter mitral valve repair using a percutaneous edge-to-edge technique is the most widely available choice at present. However, other transcatheter mitral valve repair techniques such as annuloplasty and chordal implantation are notable alternatives. Moreover, emerging technologies in transcatheter mitral valve replacement are rapidly establishing their roles in the field of chronic severe MR therapy. Hence, it is imperative to understand the indications and limitations of these various transcatheter mitral valve interventions to provide the best and most up-to-date clinical care for patients. This review will outline current evidence and patient selection criteria for such device-based therapies.

Predicting operative mortality in octogenarians for isolated coronary artery bypass grafting surgery: a retrospective study.

BACKGROUND: Available cardiac surgery risk scores have not been validated in octogenarians. Our objective was to compare the predictive ability of the Society of Thoracic Surgeons (STS) score, EuroSCORE I, and EuroSCORE II in elderly patients undergoing isolated coronary artery bypass grafting surgery (CABG). METHODS: All patients who underwent isolated CABG (2002 - 2008) were identified from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) registry. All patients aged 80 and older (n = 304) were then matched 1:2 with a randomly selected control group of patients under age 80 (n = 608 of 4732). Risk scores were calculated. Discriminatory accuracy of the risk models was assessed by plotting the areas under the receiver operator characteristic (AUC) and comparing the observed to predicted operative mortality. RESULTS: Octogenarians had a significantly higher predicted mortality by STS Score (3 ± 2% vs. 1 ± 1%; p < 0.001), additive EuroSCORE (8 ± 3% vs. 4 ± 3%; p < 0.001), logistic EuroSCORE (15 ± 14% vs. 5 ± 6%; p < 0.001), and EuroSCORE II (4 ± 3% vs. 2 ± 2%; p < 0.001) compared to patients under age 80 years. Observed mortality was 2% and 1% for patients age 80 and older and under age 80, respectively (p = 0.323). AUC revealed areas for STS, additive and logistic EuroSCORE I and EuroSCORE II, respectively, for patients age 80 and older (0.671, 0.709, 0.694, 0.794) and under age 80 (0.829, 0.750, 0.785, 0.845). CONCLUSION: All risk prediction models assessed overestimated surgical risk, particularly in octogenarians. EuroSCORE II demonstrated better discriminatory accuracy in this population. Inclusion of new variables into these risk models, such as frailty, may allow for more accurate prediction of true operative risk.

Transcatheter Valve-in-Valve: A Cautionary Tale.

Transcatheter aortic valve replacement (TAVR) by valve-in-valve (VIV) implantation is an alternative treatment for high-risk patients with a degenerating aortic bioprosthesis. We present a case of transapical TAVR VIV with a 29-mm Edwards SAPIEN XT (ESV) (Edwards Lifesciences, Irvine, CA) into a 29-mm Medtronic Freestyle stentless bioprosthesis (Medtronic Inc, Minneapolis, MN) in which unanticipated dilatation of the Freestyle bioprosthesis resulted in intraprocedural embolization of the TAVR valve, necessitating urgent conversion to a conventional surgical aortic valve replacement (AVR). Our experience suggests that TAVR VIV with the 29-mm ESV in the setting of a degenerated 29-mm Freestyle stentless bioprosthesis must be undertaken with caution.

Role of preoperative intravenous iron therapy to correct anemia before major surgery: study protocol for systematic review and meta-analysis.

BACKGROUND: Preoperative anemia is a common and potentially serious hematological problem in elective surgery and increases the risk for perioperative red blood cell (RBC) transfusion. Transfusion is associated with postoperative morbidity and mortality. Preoperative intravenous (IV) iron therapy has been proposed as an intervention to reduce perioperative transfusion; however, studies are generally small, limited, and inconclusive. METHODS/DESIGN: We propose performing a systematic review and meta-analysis. We will search MEDLINE, EMBASE, EBM Reviews, Cochrane-controlled trial registry, Scopus, registries of health technology assessment and clinical trials, Web of Science, ProQuest Dissertations and Theses, and conference proceedings in transfusion, hematology, and surgery. We will contact our study drug manufacturer for unpublished trials. Titles and abstracts will be identified and assessed by two reviewers for potential relevance. Eligible studies are: randomized or quasi-randomized clinical trials comparing preoperative administration of IV iron with placebo or standard of care to reduce perioperative blood transfusion in anemic patients undergoing major surgery. Screening, data extraction, and quality appraisal will be conducted independently by two authors. Data will be presented in evidence tables and in meta-analytic forest plots. Primary efficacy outcomes are change in hemoglobin concentration and proportion of patients requiring RBC transfusion. Secondary outcomes include number of units of blood or blood products transfused perioperatively, transfusion-related acute lung injury, neurologic complications, adverse events, postoperative infections, cardiopulmonary complications, intensive care unit (ICU) admission/readmission, length of hospital stay, acute kidney injury, and mortality. Dichotomous outcomes will be reported as pooled relative risks and 95% confidence intervals. Continuous outcomes will be reported using calculated weighted mean differences. Meta-regression will be performed to evaluate the impact of potential confounding variables on study effect estimates. DISCUSSION: Reducing unnecessary RBC transfusions in perioperative medicine is a clinical priority. This involves the identification of patients at risk of receiving transfusions along with blood conservation strategies. Of potential pharmacological blood conservation strategies, IV iron is a compelling intervention to treat preoperative anemia; however, existing data are uncertain. We propose performing a systematic review and meta-analysis evaluating the efficacy and safety of IV iron administration to anemic patients undergoing major surgery to reduce transfusion and perioperative morbidity and mortality. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015016771.

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology/Canadian Society of Cardiac Surgery position statement on revascularization--multivessel coronary artery disease.

This position statement addresses issues in revascularization for multivessel coronary artery disease (CAD) from the perspective of both cardiologists and cardiac surgeons. Recommendations are made based on evidence from clinical trials and observational studies, with an emphasis on the increasing number of individuals with significant comorbid disease burden and functional debilitation who are being referred for definitive management of their multivessel CAD in the context of routine clinical practice. These types of individuals have traditionally not been included in the many clinical trials that have been the basis for guidelines and recommendations, and the objective of the proposed medical intervention or revascularization (or both) would not necessarily be to improve prognosis but to improve quality of life. One purpose of this document is to propose practical multidisciplinary approaches to the management of these patients. Recommendations are made for revascularization in acute coronary syndromes and stable CAD, with specific considerations for individuals with left ventricular dysfunction and heart failure, chronic renal failure, and chronic obstructive pulmonary disease. We also consider the use of various risk scores, including the Society of Thoracic Surgeons score, the EuroSCORE, and the SYNTAX II score. The importance of a heart team approach is also emphasized. The complementary role of coronary bypass surgery and percutaneous coronary intervention is highlighted, along with the importance of optimal medical therapy.