Effect of Aging on Human Mesenchymal Stem Cell Therapy in Ischemic Cardiomyopathy Patients

AbstractBackgroundThe role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial.ObjectivesThis study sought to determine whether the therapeutic effect of culture-expanded MSCs persists, even in older subjects.MethodsPatients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n = 30) clinical trials were divided into 2 age groups: younger than 60 and 60 years of age and older. Functional capacity was measured by 6-min walk distance (6MWD) and quality of life using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) score, measured at baseline, 6 months, and 1 year post-TESI. Various cardiac imaging parameters, including absolute scar size, were compared at baseline and 1 year post-TESI.ResultsThe mean 6MWD was similar at baseline and increased at 1 year post-TESI in both groups: 48.5 ± 14.6 m (p = 0.001) for the younger and 35.9 ± 18.3 m (p = 0.038) for the older participants (p = NS between groups). The older group exhibited a significant reduction in MLHFQ score (−7.04 ± 3.54; p = 0.022), whereas the younger than 60 age group had a borderline significant reduction (−11.22 ± 5.24; p = 0.058) from baseline (p = NS between groups). Although there were significant reductions in absolute scar size from baseline to 1 year post-TESI, the effect did not differ by age.ConclusionsMSC therapy with TESI in ICM patients improves 6MWD and MLHFQ score and reduces myocardial infarction size. Importantly, older individuals did not have an impaired response to MSC therapy

Z-Plasty for Scar Contracture

Z-plasty is a versatile reconstructive technique used to improve the functional and aesthetic properties of scars. In addition to release wound contractures, Z-plasties are useful for primarily closing tissue defects. Z-plasties are based on tissue flaps that are marked preoperatively and raised intraoperatively to create a new central limb scar with relieved skin tension. Certain preoperative, intraoperative, and postoperative details, as described below, must be heeded to in order to prevent complications and successfully perform this procedure. Variations within this procedure exist in order to tailor to the specific needs of the reconstructive surgeon and the surrounding anatomy

Treatment Options for Exposed Calvarium Due to Trauma and Burns

Wounds involving the calvarium secondary to trauma or burns are rare. However, they can present with challenging potential clinical sequelae. A wide variety of reconstructive options have evolved over the last century. Technical aspects have progressively improved as well over time. For proper surgical restoration of function and cosmesis reconstructive surgeons must have a detailed understanding of both the scalp and skull anatomy. Several factors such as etiology of the injury, including whether or not calvarial bone defects exists or simply soft tissue loss, as well as size, local tissue environment and patient comorbidities play major roles in appropriate choice for reconstruction. Currently, there is no single treatment option for scalp or calvarial reconstruction after trauma or burns. However, reconstructive alternatives are constantly emerging with promising results

Free Versus Pedicled TRAM Flaps: Cost Utilization and Complications

Conventionally, free transverse rectus abdominis myocutaneous (fTRAM) flap breast reconstruction has been associated with decreased donor site morbidity and improved flap inset. However, clinical success depends upon more sophisticated technical expertise and facilities. This study aims to characterize postoperative outcomes undergoing free versus pedicled TRAM (pTRAM) flap breast reconstruction. Nationwide inpatient sample database (2008-2011) was reviewed for cases of fTRAM (ICD-9-CM 85.73) and pTRAM (85.72) breast reconstruction. Inclusion criteria were females undergoing pTRAM or fTRAM breast reconstruction; males were excluded. We examined demographics, hospital setting, insurance information, patient income, and comorbidities. Clinical endpoints included postoperative complications, length-of-stay (LOS), and total charges (TC). Bivariate/multivariate analyses were performed to identify independent risk factors associated with increased complications and resource utilization. Overall, 21,655 cases were captured. Seventy-percent were Caucasian, 95 % insured, and 72 % treated in an urban teaching hospital. There were 9 pTRAM and 6 fTRAM in-hospital mortalities. On bivariate analysis, the fTRAM cohort was more likely to be obese (OR 1.2), undergo revision (OR 5.9), require hemorrhage control (OR 5.7), suffer hematoma complications (OR 1.9), or wound infection (OR 1.8) (p < 0.003). The pTRAM cohort was more likely to suffer pneumonia (OR 1.6) and pulmonary embolism (OR 2.0) (p < 0.004). Reconstruction type did not affect risk of flap loss or seroma occurrence. TC were higher with fTRAM (p < 0.001). LOS was not affected by procedure type. On risk-adjusted multivariate analysis, fTRAM was an independent risk factor for increased LOS (OR 1.6), TC (OR 1.8), and postoperative complications (OR 1.3) (p < 0.001). Free TRAM has an increased risk of postoperative complications and resource utilization versus pTRAM on the current largest risk-adjusted analysis. Further analyses are required to elucidate additional factors influencing outcomes following these procedures. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A3 online Instructions to Authors. www.springer.com/00266

Latissimus dorsi flap versus pedicled transverse rectus abdominis myocutaneous breast reconstruction: outcomes

Pedicled breast reconstruction is a mainstay treatment for plastic surgeons. Although indications vary for each breast reconstruction technique, there exist some overlapping characteristics that may determine a successful outcome. We aimed to determine the impact flap selection has on postoperative outcomes and resource utilization. Nationwide Inpatient Sample database (2010-2011) was reviewed for cases of latissimus dorsi (LD; International Classification of Diseases, Ninth Revision, Clinical Modification, 85.71) and pedicled transverse rectus abdominis myocutaneous (pTRAM; 85.72) breast reconstruction. Males were excluded. Demographic, socioeconomic, clinical factors, postoperative complications, length of stay (LOS), and total charges (TC) were assessed. Chi-squared and multivariate analyses were performed to identify independent risk factors of resource utilization and postoperative complications. A total of 29,074 cases were identified; 17,670 (61%) LD and 11,405 (39%) pTRAM. 74% percent were Caucasian, 94% insured, and 66% were treated in teaching hospitals. There were 24 mortalities (15 LD, 9 pTRAM). LD patients were more likely to be obese (odds ratio [OR] = 1.3), suffer from flap loss (OR = 1.4), wound infection (OR = 1.6), wound dehiscence (OR = 2.2), and hematoma (OR = 1.3), P < 0.05. Patients undergoing pTRAM were more likely to undergo surgical revision (OR = 6.9), suffer from systemic infection (OR = 1.8), pneumonia (OR = 5.0), or pulmonary embolism (OR = 29.2), P < 0.05. Risk-adjusted multivariate analysis demonstrated LD was an independent risk factor for postoperative complication (OR = 1.4) and increased TC (OR = 1.3), P < 0.001. Conversely, undergoing pTRAM was an independent risk factor for increased LOS (OR = 6.3), P < 0.001. Analysis of a national database found LD breast reconstruction to have higher TC and increased risk for surgical site complications. Patients undergoing pTRAM had increased risk for pulmonary complications and LOS. Procedure selection may be refined as additional characteristics are discovered using outcomes-based research

Pediatric papillary thyroid carcinoma: outcomes and survival predictors in 2504 surgical patients

To evaluate outcomes and predictors of survival of pediatric thyroid carcinoma, specifically papillary thyroid carcinoma. SEER was searched for surgical pediatric cases (≤20 years old) of papillary thyroid carcinoma diagnosed between 1973 and 2011. Demographics, clinical characteristics, and survival outcomes were analyzed using standard statistical methods. All papillary types, including follicular variant, were included. A total of 2504 cases were identified. Overall incidence was 0.483/100,000 persons per year with a significant annual percent change (APC) in occurrence of 2.07 % from baseline (P < 0.05). Mean age at diagnosis was 16 years and highest incidence was found in white, female patients ages 15-19. Patients with tumor sizes <1 cm more likely received lobectomies/isthmusectomies versus subtotal/total thyroidectomies [OR = 3.03 (2.12, 4.32); P < 0.001]. Patients with tumors ≥1 cm and lymph node-positive statuses [OR = 99.0 (12.5, 783); P < 0.001] more likely underwent subtotal/total thyroidectomy compared to lobectomy/isthmusectomy. Tumors ≥1 cm were more likely lymph node-positive [OR = 39.4 (16.6, 93.7); p < 0.001]. Mortality did not differ between procedures. Mean survival was 38.6 years and higher in those with regional disease. Disease-specific 30-year survival ranged from 99 to 100 %, regardless of tumor size or procedure. Lymph node sampling did not affect survival. The incidence of pediatric papillary thyroid cancer is increasing. Females have a higher incidence, but similar survival to males. Tumors ≥1 cm were likely to be lymph node-positive. Although tumors ≥1 cm were more likely to be resected by subtotal/total thyroidectomy, survival was high and did not differ based on procedure

Surgically Treated Pediatric Nonpapillary Thyroid Carcinoma

This study aims to update outcomes and predictors of survival on pediatric thyroid carcinoma, specifically examining pediatric patients with nonpapillary thyroid carcinoma who underwent surgical resection.  Surveillance, epidemiology, and end results database were searched for pediatric cases (< 20 years old) of surgically treated nonpapillary thyroid carcinoma diagnosed from 1973 to 2011. Demographics, clinical characteristics, and survival outcomes were analyzed using standard statistical methods. All follicular, medullary, Hürthle-cell, and nonencapsulated sclerosing carcinoma types were included.  A total of 493 cases were identified. The overall incidence was 0.096/100,000 persons per year. The mean age at diagnosis was 15 years and highest incidence was found in whites, females, and patients aged 15 to 19 years. Most patients had localized (60%) or regional disease (35%) and only 38% received radiation (any type). Subtotal/total thyroidectomy was the most common procedure performed (83%) and 47% had lymph node sampling. The most common histologies were follicular (54%) and medullary (28%). Most tumors were > 2cm in size (63%). Overall 30-year survival was 91% but higher for females (94%,  = 0.02) and for local disease (92%). Disease-specific survival was highest for those with no lymph node sampling and negative lymph nodes. On multivariate analysis for medullary type only stage was an independent prognostic indicator of survival. Gender, age, tumor size, histology, and disease extent were not associated with an increased risk of mortality.  Incidence of pediatric nonpapillary thyroid cancer is low. Females have a higher incidence but similar survival to males. Stage is the only independent prognostic indicator of survival for patients with medullary thyroid cancer

New Frontiers in Psoriatic Disease Research,&nbsp;Part II: Comorbidities and Targeted Therapies

Although psoriasis and psoriatic arthritis (PsA) have been classically considered to be diseases of the skin and joints, respectively, emerging evidence suggests that a combination of innate and environmental factors creates widespread immune dysfunction, affecting multiple organ systems. A greater understanding of the pathogenesis of psoriasis and the systemic effects of psoriatic inflammation has allowed for the development of new, more effective treatments. The second portion of this two-part review series examines the comorbidities associated with psoriasis and PsA as well as the most recent advances in targeted systemic therapies for these conditions

Abstract 128: Pim1 kinase Overexpression Enhances ckit+ Cardiac Stem Cells Cardioreparative Ability After Intramyocardial Delivery

Background: Pim-1 kinase plays an important role in cell division, survival and commitment towards myocardial lineage. We hypothesized that Pim-1 overexpression in ckit+ cardiac stem cell (CSCs) enhances cardioreparative effects. Methods: Immunosuppressed Yorkshire swine (n=31) received human ckit+ CSCs (n=9), Pim1 modified human ckit+ CSCs (n=9) or PBS (n=13) two weeks after myocardial infarction. Cardiac MRI and PV loops were obtained before and after cell administration. Results: At 8 weeks post transplantation, scar mass (Fig. 1A), viable tissue (Fig. 1B), ejection fraction (Fig. 1C) and stroke work (Fig. 1D) was significantly improved in Pim-1 modified ckit+ CSC compared to control ckit+, while both cell groups showed partial recovery compared to placebo (two way ANOVA, p<0.05). Both cell types similarly reduced preload (end diastolic pressure; Fig. 1E) and afterload (Arterial elastance; Fig 1F) compared to placebo, while only administration of Pim-1 CPCs improved regional contractility at both the infarct (Fig. 1G) and border zones (Fig. 1H). Collectively, mechanoenergetic recoupling was superior in the Pim-1 group compared to ckit+ controls (Cardiac Efficiency; Fig. 1I). Conclusions: Cardioreparative potential of CSCs delivered by intramyocardial injection to infarcted porcine hearts is significantly enhanced by overexpress Pim1, supporting translational development of Pim-1 as a validated genetic modification of CSCs for incorporation into clinical trials