Search

Background Applicants to integrated plastic and reconstructive surgery (PRS) residency in the United States spend exorbitant amounts of time and money throughout the interview process. Outside of first-hand experience through a visiting rotation, applicants utilize various resources in learning about a program. Today’s applicants are “Millennials,” the demographic cohort raised during the information age and proficient with digital technology. The authors evaluated whether programs have a presence on social media, and whether applicants are following these accounts. Methods An online survey was sent to applicants to a single integrated plastic surgery program evaluating basic demographics, social media utilization, and sources of information accessed throughout the residency application process. A manual search of popular social media platforms (Instagram, Facebook, and Twitter) was performed in October 2019. Accounts affiliated with integrated PRS programs were identified and analyzed. Results Eighty-four of 222 applicants (37.8%) completed the survey. Ninety-six percent of applicants were within the Millennial demographic. Ninety-six percent of applicants had some form of social media presence, with Facebook (90%) and Instagram (87%) being the most popular platforms. Seventy-three percent of applicants reported following a PRS residency social media account. As of October 2019, 59 integrated residency programs (73%) have active Instagram accounts. Conclusions Applicants still rely on the program website when researching potential residencies, but social media is being rapidly adopted by programs. Program social media accounts should be used as a dynamic form of communication to better inform applicants of program strengths and weaknesses.

Facial burns present a challenge in burn care, as hypertrophic scarring and dyspigmentation can interfere with patients’ personal identities, ocular and oral functional outcomes, and have long-term deleterious effects. The purpose of this study is to evaluate our initial experience with non-cultured, autologous skin cell suspension (ASCS) for the treatment of deep partial-thickness (DPT) facial burns. Patients were enrolled at a single burn center during a multicenter, prospective, single-arm, observational study involving the compassionate use of ASCS for the treatment of large total BSA (TBSA) burns. Treatment decisions concerning facial burns were made by the senior author. Facial burns were initially excised and treated with allograft. The timing of ASCS application was influenced by an individual’s clinical status; however, all patients were treated within 30 days of injury. Outcomes included subjective cosmetic parameters and the number of reoperations within 3 months. Five patients (4 males, 1 female) were treated with ASCS for DPT facial burns. Age ranged from 2.1 to 40.7 years (mean 18.2 ± 17.3 years). Average follow-up was 231.2 ± 173.1 days (range 63–424 days). Two patients required reoperation for partial graft loss within 3 months in areas of full-thickness injury. There were no major complications and one superficial hematoma. Healing and cosmetic outcomes were equivalent to, and sometimes substantially better than, outcomes typical of split-thickness autografting. Non-cultured, ASCS was successfully used to treat DPT facial burns containing confluent dermis with remarkable cosmetic outcomes. Treatment of DPT burns with ASCS may be an alternative to current treatments, particularly in patients prone to dyspigmentation, scarring sequelae, and with limited donor sites.

When the COVID-19 pandemic arrived in the United States in early 2020, it caused an information explosion in the health science literature. Researchers wanted to share their results quickly, so they utilized sources that were not indexed in conventional databases. Hospital librarians stepped up to meet the information and public health challenges of the pandemic. They developed alternate strategies to provide services and resources remotely at a time when their physical libraries were closed to comply with the need for social distancing and compliance with public health recommendations.

Gut bacteria release trimethylamine (TMA) from dietary substrates. TMA is absorbed and is subsequently oxidized in the liver to produce trimethylamine N‐oxide (TMAO). Plasma TMAO levels are positively correlated with risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). High‐fat diet (HFD) consumption has been reported to increase fasting and postprandial TMAO in sedentary individuals. However, whether the increase in TMAO with consumption of an HFD is observed in endurance‐trained males is unknown. Healthy, sedentary (n = 17), and endurance‐trained (n = 7) males consumed a 10‐day eucaloric diet comprised of 55% carbohydrate, 30% total fat, and 0.05) in the sedentary and endurance‐trained group, respectively. VO2max was significantly higher in the endurance‐trained compared with sedentary males (56.7 ± 8.2 vs. 39.9 ± 6.0 ml/kg/min). Neither the HFC nor the HFD evoked a detectable change in plasma TMAO (p > 0.05) in either group. Future studies are needed to identify the effects of endurance training on TMAO production., Plasma trimethylamine N‐oxide (TMAO) levels are positively correlated with risk for cardiovascular disease and consumption of a high‐fat diet has been reported to increase TMAO. Healthy, sedentary (n = 17), and endurance‐trained (n = 7) males consumed a 10‐day eucaloric diet and a 5‐day high‐fat diet. There were no significant differences in fasting (p > 0.05) or postprandial TMAO (p > 0.05) between sedentary and endurance‐trained individuals before or following the high‐fat diet, despite the endurance‐trained group consuming more dietary precursors.

Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient proangiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n = 15) or ESA (6 μg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.

BACKGROUND: The immune response to acute ischemic stroke (AIS) is implicated in diagnosis, prognosis, and intervention; however, the temporal dynamics of leukocytes following AIS are poorly understood. The purpose of this study was to characterize peripheral leukocyte dynamics following AIS among individuals with poor and favorable outcomes. METHODS: A retrospective chart review was conducted among patients with a diagnosis of AIS who were treated at a comprehensive stroke center across a 3-year timeframe. Groups were defined according to stroke outcomes. Patients with poor outcomes were distinguished from those with favorable outcomes by discharge National Institute of Health Stroke Score, infarct size, and Modified Rankin Scale. Leukocyte counts were compared among controls and AIS outcome groups. RESULTS: The neutrophil-lymphocyte ratio (NLR) calculated at 48–72 h post-AIS was identified as the strongest predictor of outcome. NLR was significantly higher in the poor outcome group (8.68 ± 0.93) compared with both the favorable outcome (4.5 ± 0.51, p = 0.009) and control group (4.33 ± 0.66, p < 0.001). Patients with a 48–72 h NLR ≥ 4.58 were 5.58 times more likely to have a poor outcome than AIS patients with an NLR < 4.58. CONCLUSIONS: The results of this study improve the understanding of the immune response in AIS. Low neutrophil count relative to high lymphocyte count at 48–72 h post-AIS should be considered a predictor of a favorable stroke outcome. Conversely, high neutrophil count relative to low lymphocyte count at 48–72 h post-AIS should be considered a predictor of a poor stroke outcome.

The primary objective of this quality improvement project was to measure and reduce the number of oxycodone immediate-release tablets dispensed to overnight stay surgical patients at discharge. The secondary objective was to reduce the proportion of inappropriate oxycodone immediate-release prescriptions at discharge. Interrupted time series analysis was performed in four surgical wards of St Vincent's Public Hospital, Sydney. The baseline period was from January 2005 to August 2013. Interventions and follow-up occurred until July 2017. Baseline audit of oxycodone immediate-release tablet numbers showed prescribing increased significantly with a monthly linear trend of 1.8 (95%CI = 1.4-2.3; p = 0.001) tablets/100 surgical admissions from January 2005 to August 2013. Four sequential interventions produced no significant change in the primary objective. At the end of the first month of a fifth intervention, comprising audit-feedback plus individual academic detailing, the average number of oxycodone tablets decreased by 77 (95%CI 39-115) tablets/100 surgical cases, and the postintervention linear trend was a monthly reduction of 3.2 (coefficient -3.2 (95%CI -4.5 to -1.8); p = 0.001) tablets/100 surgical admissions. Baseline audit showed 27% of oxycodone prescriptions to be inappropriate. Following our intervention, this dropped to 17% (p = 0.048), and then to 10% (p = 0.002) after 3 years.

INTRODUCTION Reconstruction of soft tissue defects after skin cancer excision remains a challenge. Options for reconstruction are numerous, including primary repair, local tissue rearrangement, and skin grafts, among others. In this series, the authors present a novel technique: The triangular dart flap. This is a single-stage tissue rearrangement that uses the redundant tissue of the dog-ear to aid in the closure of these wounds. METHODS A retrospective review was conducted of all patients undergoing local tissue rearrangements by the senior author from 2009 to 2018. Factors were collected and analyzed, including age, size and cause of defect, comorbidities, smoking history, and postoperative complications. RESULTS Twenty-four patients underwent reconstruction with a triangular dart flap for repair of malignant defects. Mean defect size was 7.3 cm2 (0.8-20 cm2), and mean repair size was 29.7 cm2 (6-80 cm2). Initial pathology included basal cell carcinoma (45.8%), melanoma in situ (29.2%), and squamous cell carcinoma (16.7%), among others. Location varied widely among face and extremities. Anesthesia was predominantly local only (79.1%). There were no major complications, and 5 (20.8%) minor complications. CONCLUSIONS The triangular dart flap is a novel single-stage procedure, generally performed under local anesthesia only, for correction of Mohs defects. By using the redundant tissue of dog-ears to better approximate the wound edges, a tension-free primary closure can be achieved in sensitive areas, such as the nasal tip.

Supplemental Digital Content is available in the text., Background: The COVID-19 global pandemic has impacted plastic surgery training in the United States, requiring unprecedented measures to prepare for potential surges in critically ill patients. This study investigates how plastic surgery programs responded to this crisis, as well as how successful these changes were, through a survey of program directors and of residents at academic training programs in the United States. Methods: Two separate anonymous online surveys were conducted via REDCap between April 16 and June 4, 2020. The first survey was distributed to program directors, and the second was distributed to plastic surgery residents. Resident responses were then subdivided for an analysis between geographic regions. Results: Of the 59 program director responses (43.7%), the majority of programs implemented a platoon approach for resident coverage. A minority did the same for attending coverage. In total, 92% transitioned to virtual didactics only. Plastic surgery residents covered alternative services at 25% of responding institutions, and an additional 68% had a plan in place for responding to personnel shortages. Overall, residents were satisfied with their program’s response in a variety of categories. When subdivided based on geographic region, respondents in the Northeast and Northwest were less satisfied with resident wellness, personal and loved ones’ safety, and program communication. Conclusions: With the possibility of a “second wave,” successful methods of academic programs adapting to the pandemic should be communicated to reduce the future impact. Increased frequency of communications between program directors and residents can improve mental health and wellness of the resident population.

The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy’s potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure–volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure–volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p = 0.002). Overall, using a bioengineered hydrogel delivery system, a one-time dose of NRG delivered intramyocardially to the infarct borderzone at the time of MI in adult sheep significantly reduces scar size and enhances ventricular contractility at 8 weeks after MI.

Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). Cardiac biomechanics intricately affect long-term heart function, but whether regenerated cardiac muscle is biomechanically similar to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. C57BL/6J mice underwent sham surgery or left anterior descending coronary artery ligation at age P1 or P7. Echocardiography performed 4 weeks post-MI showed that P1 MI and sham mice (n = 22, each) had similar LV wall thickness, diameter, and ejection fraction (59.6% vs 60.7%, p = 0.6514). Compared to P7 shams (n = 20), P7 MI mice (n = 20) had significant LV wall thinning, chamber enlargement, and depressed ejection fraction (32.6% vs 61.8%, p ex vivo, and the multiaxial lenticular stress-strain relationship was tracked. While LV tissue modulus for P1 MI and sham mice were similar (341.9 kPa vs 363.4 kPa, p = 0.6140), the modulus for P7 MI mice was significantly greater than that for P7 shams (691.6 kPa vs 429.2 kPa, p = 0.0194). We conclude that, in neonatal mice, regenerated LV muscle has similar biomechanical properties as native LV myocardium.

Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p &lt, 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson&rsquo, s trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2&prime, deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI.

Objective The angiogenic potential of endothelial progenitor cells (EPCs) may be limited by the absence of their natural biologic foundation, namely smooth muscle pericytes. We hypothesized that joint delivery of EPCs and smooth muscle cells (SMCs) in a novel, totally bone marrow–derived cell sheet will mimic the native architecture of a mature blood vessel and act as an angiogenic construct to limit post infarction ventricular remodeling. Methods Primary EPCs and mesenchymal stem cells were isolated from bone marrow of Wistar rats. Mesenchymal stem cells were transdifferentiated into SMCs by culture on fibronectin-coated culture dishes. Confluent SMCs topped with confluent EPCs were detached from an Upcell dish to create a SMC-EPC bi-level cell sheet. A rodent model of ischemic cardiomyopathy was then created by ligating the left anterior descending artery. Rats were randomized into 3 groups: cell sheet transplantation (n = 9), no treatment (n = 12), or sham surgery control (n = 7). Results Four weeks postinfarction, mature vessel density tended to increase in cell sheet-treated animals compared with controls. Cell sheet therapy significantly attenuated the extent of cardiac fibrosis compared with that of the untreated group (untreated vs cell sheet, 198 degrees [interquartile range (IQR), 151-246 degrees] vs 103 degrees [IQR, 92-113 degrees], P = .04). Furthermore, EPC-SMC cell sheet transplantation attenuated myocardial dysfunction, as evidenced by an increase in left ventricular ejection fraction (untreated vs cell sheet vs sham, 33.5% [IQR, 27.8%-35.7%] vs 45.9% [IQR, 43.6%-48.4%] vs 59.3% [IQR, 58.8%-63.5%], P = .001) and decreases in left ventricular dimensions. Conclusions The bone marrow-derived, spatially arranged SMC-EPC bi-level cell sheet is a novel, multilineage cellular therapy obtained from a translationally practical source. Interactions between SMCs and EPCs augment mature neovascularization, limit adverse remodeling, and improve ventricular function after myocardial infarction.

In the last decade, numerous growth factors and biomaterials have been explored for the treatment of myocardial infarction (MI). While pre-clinical studies have demonstrated promising results, clinical trials have been disappointing and inconsistent, likely due to poor translatability. In the present study, we investigate a potential myocardial regenerative therapy consisting of a protein-engineered dimeric fragment of hepatocyte growth factor (HGFdf) encapsulated in a shear-thinning, self-healing, bioengineered hydrogel (SHIELD). We hypothesized that SHIELD would facilitate targeted, sustained intramyocardial delivery of HGFdf thereby attenuating myocardial injury and post-infarction remodeling. Adult male Wistar rats (n = 45) underwent sham surgery or induction of MI followed by injection of phosphate buffered saline (PBS), 10 μg HGFdf alone, SHIELD alone, or SHIELD encapsulating 10 μg HGFdf. Ventricular function, infarct size, and angiogenic response were assessed 4 weeks post-infarction. Treatment with SHIELD + HGFdf significantly reduced infarct size and increased both ejection fraction and borderzone arteriole density compared to the controls. Thus, sustained delivery of HGFdf via SHIELD limits post-infarction adverse ventricular remodeling by increasing angiogenesis and reducing fibrosis. Encapsulation of HGFdf in SHIELD improves clinical translatability by enabling minimally-invasive delivery and subsequent retention and sustained administration of this novel, potent angiogenic protein analog. Biotechnol. Bioeng. 2017;114: 2379-2389. © 2017 Wiley Periodicals, Inc.

Objective Inflammation has been implicated as a factor that may contribute to chronic venous insufficiency. The purpose of this study is to compare readily available inflammatory cell biomarkers, with an emphasis on neutrophil count, lymphocyte count, and neutrophil lymphocyte ratio, in patients with chronic venous insufficiency. We hypothesized that circulating leukocyte counts would be higher in the peripheral blood of patients with severe compared to mild chronic venous insufficiency. Methods We performed a retrospective medical record review of patients discharged from Ruby Memorial Hospital (Morgantown, WV, USA) with a primary diagnosis of chronic venous insufficiency. Patients were organized into two groups—mild and severe chronic venous insufficiency—based on the Clinical, Etiologic, Anatomic, and Pathophysiological classification system, and inflammatory cell counts were compared between groups. Results We observed a significantly higher neutrophil count ( p = .002) and neutrophil-lymphocyte ratio ( p = .005) in patients with severe chronic venous insufficiency compared to mild. Further, the neutrophil–lymphocyte ratio may be a useful predictor of chronic venous insufficiency severity. Conclusions We reported significant differences in inflammatory cell biomarkers between mild and severe chronic venous insufficiency, as well as provided support for the use of the neutrophil–lymphocyte ratio as a predictor of chronic venous insufficiency severity. These results may provide clinicians with additional insight to manage chronic venous insufficiency in patients and provide a framework for the development of novel treatment options targeting the immune system in chronic venous insufficiency.

Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.

Introduction: Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) until postnatal day 7 (P7). Whether this regenerated muscle is similar biomechanically to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. Methods: C57BL/6J mice (n=58) underwent sham surgery or left anterior descending coronary artery ligation on postnatal day 1 (P1) or P7. After 4 weeks, echocardiography was performed. The explanted anterolateral LV wall was mounted for lenticular hydrostatic deformation testing (Fig 1A-B) and pressurized to 130 mmHg with 37°C saline to impart a homogeneous stress load. Surface strain was tracked to calculate a multiaxial composite tissue modulus. Data are expressed as mean±SEM. Results: P1 MI and sham mice (n=14, each) had similar post-MI LV wall thickness (0.61±0.05 cm vs 0.66±0.03 cm, p=0.39), end-diastolic diameter (3.14±0.10 cm vs 3.05±0.12 cm, p=0.57), and ejection fraction (58.2±4.1% vs 55.2±4.4%, p=0.63). P7 MI mice (n=14) had significant LV wall thinning (0.40±0.04 cm vs 0.71±0.02 cm, p Conclusion: In a neonatal mouse MI model, regenerated LV muscle has similar biomechanical properties as native LV muscle.

Background Despite the landmark study by Godina 30 years ago, opinions still vary within the literature about the management of complex traumatic wounds in the lower extremity. We present a large series of lower extremity reconstructions with vascularized free tissue and examine the perioperative factors that influenced the success of these cases. Methods We reviewed 88 patients with free flap reconstruction of traumatic lower extremity wounds over 8 years. Primary outcomes were flap infections, flap loss, total flap-specific complications, and total recipient site complications. Independent variables specific to perioperative care including time to flap coverage, injury classification, exposed or infected hardware, prior osteomyelitis, use of wound vacuum-assisted closure (VAC) therapy, and concurrent polytrauma were investigated to establish their influence on primary outcomes. Each independent variable was assessed using Chi-square or Fisher's exact test and was included in a logistic regression analysis to establish significance. Results Of the 88 patients, 8 had flap loss, 8 had flap infections, and a total of 23 had primary adverse outcomes. Timing of the reconstruction, VAC use, injury classification, prior hardware or wound status, or presence of polytrauma had no statistically significant impact on the primary outcomes. Injury classification/severity on total recipient site complications (p = 0.051) and flap-specific complications (p = 0.073) trended toward significance; however, subgroup analysis did not achieve significance. Logistic regression of any recipient site complication including all independent variables similarly showed no significance. Conclusion Although the original study by Godina suggests early coverage is critical to optimize outcomes, in the modern era of advanced wound care, our study adds to a growing body of evidence that supports the de-emphasis of the 72-hour reconstruction interval. Our current management is focused on more effectively coordinating efficient peritraumatic and perioperative care on an individualized basis in the often very complicated polytrauma patient.

Cardiovascular disease remains the leading cause of morbidity and mortality in the United States and worldwide. While improvements in prevention strategies and secondary interventions have led to enhanced survival, many patients still succumb to heart failure. This necessitates the development of novel strategies to target the microvascular dysfunction and malperfusion which lead to progressive functional deterioration. Cardiovascular tissue engineering strategies represent an important class of therapeutics which aim to address the insufficiencies of current management of heart failure and related sequelae. Here, we review the various tissue engineering strategies which address the limitations of current therapies and represent promising adjunct treatments to the current gold standard.

During the last 2 decades, there has been a surge in the development of stem cell therapies to treat numerous debilitating diseases. Cardiovascular disease is a leading target of this research because of the minimal proliferative and regenerative capabilities of the heart. These studies have quickly progressed to clinical trials; however, the initial enthusiasm has faded because outcomes from these studies have led to disappointing and inconsistent results.1 This viewpoint offers an explanation as to why stem cells have yet to demonstrate a significant benefit in patients having cardiovascular disease and how these challenges should be addressed. It is currently unknown which cell lineage provides the greatest potential in regenerative effects. While most cardiac clinical trials have delivered mesenchymal stem cells or bone marrow–derived stem cells (BMSCs), others have used adipose-derived stem cells (ASCs) and cardiac stem cells (CSCs).1,2 Yet, regardless of the cell type used, stem cell trials for cardiovascular diseases have not yielded clinically meaningful outcomes, though most have only been statistically powered to demonstrate feasibility and safety. Mesenchymal stem cells are advantageous because they can be delivered to patients without the need for immunosuppression and secrete numerous antiapoptotic and angiogenic growth factors.3 In 2014, 30 patients were enrolled in a multicenter, double-blind trial and randomized to receive an intramyocardial injection of 25 million mesenchymal stem cells or cell medium concurrent with left ventricular assist device implantation. The authors concluded that administration of mesenchymal stem cells was feasible and safe, with a trend toward functional efficacy.3 BMSCs are commonly administered in cardiac trials and are attractive because of their proven safety and paracrine effects.4 A BMSC trial published in 2013 randomized 200 patients with acute myocardial infarction to an open-labeled, controlled trial with 2 BMSC groups. These cells were administered via …

Background: Cardiovascular bypass grafting is an essential treatment for complex cases of atherosclerotic disease. Because the availability of autologous arterial and venous conduits is patient-limited, self-assembled cell-only grafts have been developed to serve as functional conduits with off-the-shelf availability. The unacceptably long production time required to generate these conduits, however, currently limits their clinical utility. Here, we introduce a novel technique to significantly accelerate the production process of self-assembled engineered vascular conduits. Methods: Human aortic smooth muscle cells and skin fibroblasts were used to construct bilevel cell sheets. Cell sheets were wrapped around a 22.5-gauge Angiocath needle to form tubular vessel constructs. A thin, flexible membrane of clinically approved biodegradable tissue glue (Dermabond Advanced) served as a temporary, external scaffold, allowing immediate perfusion and endothelialization of the vessel construct in a bioreactor. Subsequently, the matured vascular conduits were used as femoral artery interposition grafts in rats (n=20). Burst pressure, vasoreactivity, flow dynamics, perfusion, graft patency, and histological structure were assessed. Results: Compared with engineered vascular conduits formed without external stabilization, glue membrane–stabilized conduits reached maturity in the bioreactor in one-fifth the time. After only 2 weeks of perfusion, the matured conduits exhibited flow dynamics similar to that of control arteries, as well as physiological responses to vasoconstricting and vasodilating drugs. The matured conduits had burst pressures exceeding 500 mm Hg and had sufficient mechanical stability for surgical anastomoses. The patency rate of implanted conduits at 8 weeks was 100%, with flow rate and hind-limb perfusion similar to those of sham controls. Grafts explanted after 8 weeks showed a histological structure resembling that of typical arteries, including intima, media, adventitia, and internal and external elastic membrane layers. Conclusions: Our technique reduces the production time of self-assembled, cell sheet–derived engineered vascular conduits to 2 weeks, thereby permitting their use as bypass grafts within the clinical time window for elective cardiovascular surgery. Furthermore, our method uses only clinically approved materials and can be adapted to various cell sources, simplifying the path toward future clinical translation.

Introduction: Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, ultimately leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Methods: Male Wistar rats (n=46) underwent sham surgery (n=15) or permanent left anterior descending coronary artery ligation (n=31). Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n=15) or ESA (6 μg/kg, n=16), delivered at standardized peri-infarct sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Biaxial tensile testing of the anterior LV wall was performed using a strain-controlled biaxial load frame (Fig. 1A), producing up to physiologic circumferential and longitudinal strains (ε=20%, each). The modulus was determined along each axis, and maximum shear stress was calculated as a composite metric of the tissue’s response to physiologic strains. Data are expressed as mean±SEM. Results: At 4 weeks post-MI, ESA-treated hearts had smaller end-diastolic LV internal dimension (6.89±0.27 cm vs 7.69±0.22 cm, p=0.03) and improved ejection fraction (63.7±2.9% vs 49.4±4.4%, p=0.01) compared to saline-injected controls. Hearts treated with ESA exhibited lower moduli than saline controls in both the circumferential (269.4±33.2 kPa vs 431.5±55.6 kPa, p=0.02) and longitudinal axes (182.4±25.0 kPa vs 332.3±51.2 kPa, p=0.02, Fig. 1B). The maximum shear stress for ESA-treated hearts was significantly reduced compared to that for saline controls (5.8±0.8 kPa vs 9.0±1.2 kPa, p=0.03) and was similar to that for sham controls (Fig. 1C). Conclusion: Intramyocardial ESA injection mitigates post-MI tissue stiffening and preserves biaxial LV mechanical properties.

Introduction: The posterior ventricular anchoring neochordal (PVAN) repair is a nonresectional, single-suture technique for correcting posterior leaflet prolapse. While this technique has demonstrated clinical efficacy, a possible limitation is the stability of the suture anchored into myocardium as opposed to the fibrous portion of a papillary muscle. Hypothesis: We hypothesize that the PVAN suture serves only to position the leaflet for coaptation, after which systolic forces will be distributed throughout the valve, resulting in low peak forces on the suture. Methods: A left heart simulator was constructed using 3D printing, tuned to generate physiological pressure and flow waveforms, then validated. Porcine mitral valves (n=9) were dissected and mounted within the simulator. Chordal forces were measured using Fiber Bragg Grating (FBG) sensors, sewn in place using PTFE suture. FBG sensors are strain gauges made of 125 μ m optical fibers that use reflected peak wavelength changes to measure strain. Hemodynamic and echocardiographic data were also collected. Isolated severe mitral regurgitation (MR) was induced by cutting P2 primary chordae. The valve was repaired using the PVAN technique, anchoring the suture to a customized force-sensing post positioned to mimic in vivo placement. Results: Forces on 1° and 2° chordae of both anterior and posterior leaflets were significantly elevated in the prolapse condition ( P < 0.05). PVAN resulted in elimination of MR in all valves, as well as normalization of chordae forces to baseline levels for posterior primary ( P < 0.01 ) , posterior secondary ( P < 0.01 ) , and anterior primary chordae ( P < 0.05 ) , with reduction in anterior secondary chordal forces approaching significance ( P = 0.055 ) . Peak forces on the PVAN stitch were minimal, even compared to the forces experienced by primary chordae of normal, healthy valves ( P < 0.05). Conclusions: The PVAN technique eliminates MR by effectively positioning the posterior leaflet for optimal coaptation, distributing the forces amongst the subvalvular apparatus. Given the extremely low forces involved, the strength of the ventricular anchoring suture and myocardial anchoring point should not be a limiting factor.

The gut microbiome metabolizes choline and carnitine to release trimethylamine (TMA), which subsequently undergoes hepatic conversion to trimethylamine N-oxide (TMAO). Elevated TMAO levels are associated with cardiovascular disease and all-cause mortality risk. Dietary flavanols modulate the composition and function of the gut microbiome. Therefore, the possibility exists that these compounds could reduce intestinal TMA production and lower circulating TMAO. However, this hypothesis has never been tested in humans. A secondary analysis was performed on blood samples from a clinical study in which obese subjects at risk for insulin resistance consumed tea or cocoa flavanols in a randomized crossover design while consuming a controlled diet. These subjects generally had elevated TMAO levels (approximate to 5 M) compared to levels previously measured in healthy subjects (approximate to 1 M). None of the interventions significantly altered TMAO levels. Individual variability for choline and carnitine was relatively low. However, TMAO exhibited somewhat greater inter-individual variability. No differences in mean TMAO concentrations observed across interventions were seen based on separating subjects by glycemic status, body mass index (BMI), race, age, or gender. However, subject minimum and maximum values observed across the interventions appeared to be more strongly associated with glycemic status and age than mean values across interventions, suggesting that average TMAO values over time may be less useful than maximum or minimum values as markers of disease risk. Traditional physiological characteristics do not appear to predict TMAO responsiveness to flavanol interventions. However, African-American subjects appeared less responsive compared to non-Hispanic white subjects for both green tea and high cocoa treatments, and female subjects appeared less responsive than males for the high cocoa treatment. The present results suggest that a short-term flavanol intervention does not generally reduce fasting TMAO levels in subjects with elevated circulating TMAO. Virginia Agricultural Experiment Station; Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture; U.S. Department of AgricultureUnited States Department of Agriculture (USDA); Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education program (TOR IGEP) Funding for the present work was provided, in part, by the Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture (APN, KPD). Funding for the original study was provided by the U.S. Department of Agriculture (DJB, JAN). Funding for LEG was provided by the Virginia Tech Translational Obesity Research Interdisciplinary Graduate Education program (TOR IGEP). Public domain – authored by a U.S. government employee

Background: \ud We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients.\ud \ud Patients and methods: \ud In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7 days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7 days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small-cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively.\ud \ud Results: \ud The dose-escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. On the basis of toxicity and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion, RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively, with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28–18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%), and the mPFS was 5.8 months (95% CI: 2.76–21.25).\ud \ud Discussion: \ud In this phase I trial, we report a highly active and well-tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC.\ud \ud Clinical trial registration: \ud ClinicialTrials.gov identifier: CNCT02193633.

Objective The optimal conduit for valve-sparing aortic root replacement is still debated, with several conduit variations available, ranging from straight tubular grafts to Valsalva grafts. Benefits of neosinus reconstruction include enhanced flow profiles and improved hemodynamics. Curiously, however, some clinical data suggest that straight grafts may have greater long-term durability. In this study, we hypothesized that straight tubular grafts may help maintain the native cylindrical position of the aortic valve commissures radially, resulting in preserved leaflet coaptation, reduced stresses, and potentially improved valve performance. Methods Using 3D printing, a left heart simulator with a valve-sparing root replacement model and a physiologic coronary circulation was constructed. Aortic valves were dissected from fresh porcine hearts and reimplanted into either straight tubular grafts (n = 6) or Valsalva grafts (n = 6). Conduits were mounted into the heart simulator and hemodynamic, echocardiographic, and high-speed videometric data were collected. Results Hemodynamic parameters and coronary blood flow were similar between straight and Valsalva grafts, although the former were associated with lower regurgitant fractions, less peak intercommissural radial separation, preserved leaflet coaptation, decreased leaflet velocities, and lower relative leaflet forces compared with Valsalva grafts. Conclusions Valsalva grafts and straight grafts perform equally well in terms of gross hemodyanics and coronary blood flow. Interestingly, however, the biomechanics of these 2 conduits differ considerably, with straight grafts providing increased radial commissural stability and leaflet coaptation. Further investigation into how these parameters influence clinical outcomes is warranted.

Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

Background: Inhospital stroke (IHS) is defined as an acute ischemic infarction that occurs during hospitalization in a patient originally admitted for another diagnosis or procedure. Approximately 4 to 17 percent of all adult strokes are IHS, and most IHS occurs in cardiologic and cardiosurgical patients after catheterization or surgery. Time to brain imaging is longer in IHS vs community onset strokes (COS) due to delayed symptom recognition, and consequently, IHS patients have greater disability and increased mortality comparted to their COS counterparts. Purpose: The purpose of this project was to educate cardiac nurses to more rapidly and accurately recognize symptoms of acute ischemic stroke. We hypothesized that this education would shorten evaluation time for inpatient strokes and result in faster activation of the Code Stroke team. Methods: Two 4-hour “Heart to Brain Connection” seminars were offered. Course objectives targeted development of critical thinking regarding the relationship of cardiovascular and cerebrovascular disease. Content included cardiac and cerebral anatomy, recognition of ischemic stroke syndromes and NIH Stroke Scale review. All cardiac nurses completed NIH Stroke Scale Certification. Nurses were empowered to call a “Code Stroke” and educated on appropriate criteria. NIH Stroke Scale pocket cards and pencils with the code stroke number were distributed through the cardiac units. Results: We compared the median time from stroke symptom recognition to activation of “Code Stroke” before and after our interventions. Prior to the interventions, in 2014, the median time was 20 minutes; however, this time was decreased to 6.5 minutes in 2016 following our interventions. Further, in 2014, only 36 percent of “Code Strokes” were called by nurses. Following the interventions, “Code Strokes” were called by cardiac nurses in 75 percent of cases in 2016. Conclusions: Empowering cardiac nurses to call a “Code Stroke“ through targeted education and training increases the number of “Code Strokes” called by nurses and decreases the time from recognition to activation of the Code Stroke team thereby optimizing the patient’s potential outcome.

Severe burn injury results in a multifaceted physiological response that significantly alters drug pharmacokinetics and pharmacodynamics (PK/PD). This response includes hypovolemia, increased vascular permeability, increased interstitial hydrostatic pressure, vasodilation, and hypermetabolism. These physiologic alterations impact drug distribution and excretion-thus varying the drug therapeutic effect on the body or microorganism. To this end, in order to optimize critical care for the burn population it is essential to understand how burn injury alters PK/PD parameters. The purpose of this article is to describe the relationship between burn injury and drug PK/PD. We conducted a literature review via PubMed and Google to identify burn-related PK/PD studies. Search parameters included "pharmacokinetics," "pharmacodynamics," and "burns." Based on our search parameters, we located 38 articles that studied PK/PD parameters specifically in burns. Twenty-seven articles investigated PK/PD of antibiotics, 10 assessed analgesics and sedatives, and one article researched an antacid. Out of the 37 articles, there were 19 different software programs used and eight different control groups. The mechanisms behind alterations in PK/PD in burns remain poorly understood. Dosing techniques must be adapted based on burn injury-related changes in PK/PD parameters in order to ensure drug efficacy. Although several PK/PD studies have been undertaken in the burn population, there is wide variation in the analytical techniques, software, and study sample sizes used. In order to refine dosing techniques in burns and consequently improve patient outcomes, there must be harmonization among PK/PD analyses.

Background Diabetes mellitus is a risk factor for coronary artery disease and diabetic cardiomyopathy, and adversely impacts outcomes following coronary artery bypass grafting. Current treatments focus on macro-revascularization and neglect the microvascular disease typical of diabetes mellitus-induced cardiomyopathy (DMCM). We hypothesized that engineered smooth muscle cell (SMC)-endothelial progenitor cell (EPC) bi-level cell sheets could improve ventricular dysfunction in DMCM. Methods Primary mesenchymal stem cells (MSCs) and EPCs were isolated from the bone marrow of Wistar rats, and MSCs were differentiated into SMCs by culturing on a fibronectin-coated dish. SMCs topped with EPCs were detached from a temperature-responsive culture dish to create an SMC-EPC bi-level cell sheet. A DMCM model was induced by intraperitoneal streptozotocin injection. Four weeks after induction, rats were randomized into 3 groups: control (no DMCM induction), untreated DMCM, and treated DMCM (cell sheet transplant covering the anterior surface of the left ventricle). Results SMC-EPC cell sheet therapy preserved cardiac function and halted adverse ventricular remodeling, as demonstrated by echocardiography and cardiac magnetic resonance imaging at 8 weeks after DMCM induction. Myocardial contrast echocardiography demonstrated that myocardial perfusion and microvascular function were preserved in the treatment group compared with untreated animals. Histological analysis demonstrated decreased interstitial fibrosis and increased microvascular density in the SMC-EPC cell sheet-treated group. Conclusions Treatment of DMCM with tissue-engineered SMC-EPC bi-level cell sheets prevented cardiac dysfunction and microvascular disease associated with DMCM. This multi-lineage cellular therapy is a novel, translatable approach to improve microvascular disease and prevent heart failure in diabetic patients.

Reduction mammaplasty is one of the most commonly performed plastic surgery operations. For a majority of techniques, the most common long-term complication is pseudoptosis. It has previously been proposed that upper breast suspensory ligaments (SL) are weaker than lower breast SL. We tested this hypothesis through anthropometry of the proxies for upper and lower SL strength: the sternal notch-nipple (SN-N) distance and the nipple-inframammary fold (N-IMF) distance, respectively.An institutional review board-approved retrospective review of patients undergoing reduction mammoplasty in an academic faculty practice between 2008 and 2015 was conducted. Patient demographics included age, race, and body mass index (BMI); patient comorbidities included smoking status, diabetes, and hypertension. Breast anthropometric measurements included SN-N and N-IMF. Sternal notch-nipple was used as the primary metric of the upper SL strength, whereas N-IMF was used as the primary metric of the lower SL strength. Intraoperative details included reduction technique and resection mass. Postoperative complications were recorded, including nipple areola complex necrosis and hematoma. Linear regression analysis was performed with the primary endpoint of the relationship between SN-N and N-IMF distance in macromastia.Data from 208 patients, totaling 400 individual breast measurements, were collected. The mean SN-N length was 35.1 cm, mean N-IMF length was 16.0 cm, and mean resection weight was 1094 g. Linear regression found that N-IMF distance could be predicted as 45% of the SN-N distance (N-IMF = 0.454 * SN-N). This was a strong relationship, demonstrated by univariate analysis of SN-N and N-IMF (R, 0.624; P0.001). A Wise pattern was used in 89.9% of cases; an inferior pedicle was used in 83.7% of cases. Nipple areola complex necrosis occurred in 15 breasts (3.75%). Sternal notch-nipple (R, 0.127; P = 0.011) and N-IMF (R, 0.119; P = 0.017) were both predictive of nipple areola complex necrosis (Table 4).In our series, the N-IMF distance increased 0.45 cm for every 1 cm increase in the SN-N distance. This relationship strengthens our primary hypothesis that the lower pole ligaments stretch at a significantly slower rate than the upper pole ligaments. Taking this into consideration, we suggest that surgeons seeking to minimize pseudoptosis rates should favor techniques that minimally disrupt the lower SL.

Over the past two decades, the field of cardiovascular medicine has seen the rapid development of multiple different modalities for the treatment of ischemic myocardial disease. Most research efforts have focused on strategies aimed at coronary revascularization, with significant technological advances made in percutaneous coronary interventions as well as coronary artery bypass graft surgery. However, recent research efforts have shifted towards ways to address the downstream effects of myocardial infarction on both cellular and molecular levels. To this end, the broad application of injectable hydrogel therapy after myocardial infarction has stimulated tremendous interest. In this article, we will review what hydrogels are, how they can be bioengineered in unique ways to optimize therapeutic potential, and how they can be used as part of a treatment strategy after myocardial infarction.

Background Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. Methods The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. Results In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. Conclusions rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

Solar-powered heart? Harnessing light to create myocardial renewable energy., Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.

Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

ObjectivesThe goal of this study was to retrospectively evaluate the clinical impact of an accurate autocorrecting blood glucose monitoring system in children with severe burns. Blood glucose monitoring system accuracy is essential for providing appropriate intensive insulin therapy and achieving tight glycemic control in critically ill patients. Unfortunately, few comparison studies have been performed to evaluate the clinical impact of accurate blood glucose monitoring system monitoring in the high-risk pediatric burn population.DesignRetrospective analysis of an electronic health record system.SettingPediatric burn ICU at an academic medical center.PatientsChildren (aged < 18 yr) with severe burns (≥ 20% total body surface area) receiving intensive insulin therapy guided by either a noncorrecting (blood glucose monitoring system-1) or an autocorrecting blood glucose monitoring system (blood glucose monitoring system-2).Measurements and main resultsPatient demographics, insulin rates, and blood glucose monitoring system measurements were collected. The frequency of hypoglycemia and glycemic variability was compared between the two blood glucose monitoring system groups. A total of 122 patient charts from 2001 to 2014 were reviewed. Sixty-three patients received intensive insulin therapy using blood glucose monitoring system-1 and 59 via blood glucose monitoring system-2. Patient demographics were similar between the two groups. Mean insulin infusion rates (5.1 ± 3.8 U/hr; n = 535 paired measurements vs 2.4 ± 1.3 U/hr; n = 511 paired measurements; p < 0.001), glycemic variability, and frequency of hypoglycemic events (90 vs 12; p < 0.001) were significantly higher in blood glucose monitoring system-1-treated patients. Compared with laboratory measurements, blood glucose monitoring system-2 yielded the most accurate results (mean ± SD bias: -1.7 ± 6.9 mg/dL [-0.09 ± 0.4 mmol/L] vs 7.4 ± 13.5 mg/dL [0.4 ± 0.7 mmol/L]). Blood glucose monitoring system-2 patients achieve glycemic control more quickly (5.7 ± 4.3 vs 13.1 ± 6.9 hr; p< 0.001) and stayed within the target glycemic control range longer compared with blood glucose monitoring system-1 patients (85.2% ± 13.9% vs 57.9% ± 29.1%; p < 0.001).ConclusionsAccurate autocorrecting blood glucose monitoring system optimizes intensive insulin therapy, improves tight glycemic control, and reduces the risk of hypoglycemia and glycemic variability. The use of an autocorrecting blood glucose monitoring system for intensive insulin therapy may improve glycemic control in severely burned children.

The purpose of this study was to develop a faster approach to phase contrast magnetic resonance imaging. This article proposes a phase contrast imaging scheme called single scan phase contrast in which the polarity of the velocity-encoding gradient is alternated between phase encoding steps. In single scan phase contrast, ghost images due to moving spins form. The signal intensity of the ghost images is modulated by the sine of the motion-induce phase shift. Prior to image acquisition, the region of interest containing moving spins is identified, and the field of view is configured so to avoid overlap between the object in the image and the ghost image(s) due to motion in the region of interest. The image values of the region of interest and the ghost image are used to quantify velocity. At best, single scan phase contrast reduces the total acquisition time by a factor of two when compared to phase contrast. In this study, single scan phase contrast is validated against phase contrast in phantom and in vivo. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.

Objective Although the mammalian heart's ability to fully regenerate is debated, its potential to extensively repair itself is gaining support. We hypothesized that heart regeneration relies on rapid angiogenesis to support myocardial regrowth and sought to characterize the timeline for angiogenesis and cell proliferation in regeneration. Methods One-day-old CD-1 mice (P1, N = 60) underwent apical resection or sham surgery. Hearts were explanted at serial time points from 0 to 30 days postresection and analyzed with immunohistochemistry to visualize vessel ingrowth and cardiomyocyte migration into the resected region. Proliferating cells were labeled with 5-ethynyl-2′-deoxyuridine injections 12 hours before explant. 5-Ethynyl-2′-deoxyuridine–positive cells were counted in both the apex and remote areas of the heart. Masson's trichrome was used to assess fibrosis. Results By 30 days postresection, hearts regenerated with minimal fibrosis. Compared with sham surgery, apical resection stimulated a significant increase in proliferation of preexisting cardiomyocytes between 3 and 11 days after injury. Capillary migration into the apical thrombus was detected as early as 2 days postresection, with development of mature arteries by 5 days postresection. New vessels became perfused by 5 days postresection as evidenced by lectin injection. Vessel density and diameter significantly increased within the resected area over 21 days, and vessel ingrowth always preceded cardiomyocyte migration, with coalignment of most migrating cardiomyocytes with ingrowing vessels. Conclusions Endothelial cells migrate into the apical thrombus early after resection, develop into functional arteries, and precede cardiomyocyte ingrowth during mammalian heart regeneration. This endogenous neonatal response emphasizes the importance of expeditious angiogenesis required for neomyogenesis.

INTRODUCTION The fast-track assessment clinic (FTAC) is a process to select patients who are very likely to require primary total hip replacement. Selected patients can then be seen in a one-off clinic reducing the number of hospital visits, cost to primary care trusts and delay between referral and treatment. PATIENTS AND METHODS Fifty patients on the waiting list for hip replacement were analysed to see if there were common parameters that led to their inclusion. From these data, fast-track selection criteria (FTSCs) were generated. These FTSCs were used to make a dual comparison of outcomes between 52 patients seen in a traditional clinic. Finally, a pilot study was conducted in which patients fulfilling FTSCs were seen in a designated clinic. RESULTS An Oxford hip score (OHS) of 34 and above combined with severe loss of joint space, severe marginal osteophytes, or both was common to most patients on the waiting list (84%). FTSCs correctly predicted the outcome of the orthopaedic clinic in 38 patients out of a total of 52. During the pilot stage, positive FTSCs were shown to have a positive predictive value of 92% for joint replacement being carried out and a negative predictive value of 46%. CONCLUSIONS An OHS of 34 or above combined with complete loss of joint space and/or severe marginal osteophyte formation can be used to select patients who are very likely to need total hip replacement. These patients can be seen in a clinic that combines assessment of surgical indication with medical fitness for surgery.

Background Early detection of acute kidney injury (AKI) in severely burn-injured patients can help alter treatment to prevent progression to acute failure and reduce the need for renal replacement therapy. We hypothesized that whole blood neutrophil gelatinase–associated lipocalin (NGAL) will be increased in severely burn-injured patients who develop AKI during acute resuscitation. Materials and methods We performed a prospective observation study of adult burn patients with a 20% total body surface area (TBSA) burned or greater burn injury. Two-hour serial measurements of NGAL, serum creatinine (Cr), and hourly urine output (UO) were collected for 48 h after admission. Our primary goal was to correlate the risk of AKI in the first week after burn injury with serial NGAL levels in the first 48 h after admission. Our secondary goal was to determine if NGAL was an earlier independent predictor of AKI compared with Cr and UO. Results We enrolled 30 adult (age ≥ 18 y) burn patients with the mean ± standard deviation age of 40.9 ± 15.4 and mean TBSA of 46.4 ± 22.4. Fourteen patients developed AKI within the first 7 d after burn injury. There were no differences in age, TBSA, fluid administration, mean arterial pressure, UO, and Cr between AKI and no-AKI patients. NGAL was significantly increased as early as 4 h after injury (182.67 ± 83.3 versus 107.37 ± 46.15) in the AKI group. Controlling for age, TBSA, and inhalation injury, NGAL was a predictor of AKI at 4 h after injury (odds ratio, 1.02) and remained predictive of AKI for the period of more than the first 24 h after admission. UO and Cr were not predictive of AKI in the first 24 h after admission. Conclusions Whole blood NGAL is markedly increased in burn patients who develop AKI in the first week after injury. In addition, NGAL is an early independent predictor of AKI during acute resuscitation for severe burn injury. UO and Cr are not predictive of AKI during this time period.

We prospectively studied the outcome of a protocol of prophylaxis for deep vein thrombosis (DVT) in 103 consecutive patients undergoing surgical stabilisation of pelvic and acetabular fractures. Low-molecular-weight heparin (LMWH) was administered within 24 hours of injury or on achieving haemodynamic stability. Patients were screened for proximal DVT by duplex ultrasonography performed ten to 14 days after surgery. The incidence of proximal DVT was 10% and of pulmonary embolus 5%. Proximal DVT developed in two of 64 patients (3%) who had received LMWH within 24 hours of injury, but in eight of 36 patients (22%) who received LMWH more than 24 hours after the injury (p < 0.01). We conclude that LMWH, when begun without delay, is a safe and effective method of thromboprophylaxis in high-risk patients with major pelvic or acetabular fractures.