Citations

Obesity associated with metabolic derangements (ObM) worsens the prognosis of patients with coronary artery stenosis (CAS), but the underlying cardiac pathophysiologic mechanisms remain elusive. We tested the hypothesis that ObM exacerbates cardiomyocyte loss distal to moderate CAS. Obesity-prone pigs were randomized to four groups ( n = 6 each): lean-sham, ObM-sham, lean-CAS, and ObM-CAS. Lean and ObM pigs were maintained on a 12-wk standard or atherogenic diet, respectively, and left circumflex CAS was then induced by placing local-irritant coils. Cardiac structure, function, and myocardial oxygenation were assessed 4 wk later by computed-tomography and blood oxygenation level dependent (BOLD) MRI, the microcirculation with micro-computed-tomography, and injury mechanisms by immunoblotting and histology. ObM pigs showed obesity, dyslipidemia, and insulin resistance. The degree of CAS (range, 50–70%) was similar in lean and ObM pigs, and resting myocardial perfusion and global cardiac function remained unchanged. Increased angiogenesis distal to the moderate CAS observed in lean was attenuated in ObM pigs, which also showed microvascular dysfunction and increased inflammation (M1-macrophages, TNF-α expression), oxidative stress (gp91), hypoxia (BOLD-MRI), and fibrosis (Sirius-red and trichrome). Furthermore, lean-CAS showed increased myocardial autophagy, which was blunted in ObM pigs (downregulated expression of unc-51-like kinase-1 and autophagy-related gene-12; P < 0.05 vs. lean CAS) and associated with marked apoptosis. The interaction diet xstenosis synergistically inhibited angiogenic, autophagic, and fibrogenic activities. ObM exacerbates structural and functional myocardial injury distal to moderate CAS with preserved myocardial perfusion, possibly due to impaired cardiomyocyte turnover.

ObjectivesAnalyze the effect of ipsilateral submandibular gland preservation on patients undergoing concurrent neck dissection and transoral surgery for oropharyngeal squamous cell carcinoma. Evaluate for (1) intraoperative and postoperative communications between the oropharynx and neck and (2) oncologic outcomes.Study DesignRetrospective chart review of prospectively collected data.SettingTertiary academic referral center.Methods and SubjectsRetrospective chart review of patients undergoing transoral laser resection of oropharyngeal squamous cell carcinoma with simultaneous neck dissection(s) for primary, persistent, recurrent, and second primary disease between January 1999 and February 2013. Data analyzed for operative technique, pathologic diagnosis, postoperative course, complications, and oncologic outcomes.ResultsOverall 253 patients were identified. Of these, 96 patients underwent ipsilateral submandibular gland preservation and 157 underwent ipsilateral submandibular gland removal at the time of neck dissection. The prevalence of intraoperative communication between the neck and oropharynx was significantly lower in cases with submandibular gland preservation (2/96, 2.08%) compared to those with submandibular gland removal (22/157, 14.13%). No postoperative leaks occurred in the gland preservation group (0/96, 0%) compared to a leak prevalence of 8.92% (14/157) when the gland was removed (P =. 0041). There was no difference in local, regional, or distant disease recurrence between submandibular gland preservation and gland removal. Similarly, Kaplan‐Meier analysis showed no difference in disease free survival, disease specific survival, or overall survival.ConclusionsSubmandibular gland preservation during neck dissection in patients undergoing transoral surgery for oropharyngeal squamous cell carcinoma significantly reduces the risk of intraoperative and postoperative salivary leaks without compromising oncologic outcomes.

Background: Telemedical physician triage (TPT) is a potential application of telemedicine in the emergency department (ED). We report the technical success, patient satisfaction, and effect on ED throughput metrics (length of stay [LOS] and time to physician evaluation [TPE]) of TPT performed on a mobile platform. Materials and Methods: Patients underwent standard nursing triage with or without TPT. Technical success is reported as raw data. Patient satisfaction is reported as raw data±standard deviation on a 5-point (low-to-high) scale. LOS and TPE are reported as mean±SD [95% CI] values. Statistical analyses of LOS and TPE are via two-sample t test. Results: One hundred six patients were registered during intervention periods, and TPT was completed in 36 (34%). One hundred ninety-six patients were registered during control periods. The technical success rate was 95%. Average patient satisfaction was 4.7 on a 5-point scale. The primary analysis (106 patients) showed no change in LOS (266±101 [244–288] min versus 258±172 [234–282] min) but a trend toward improved TPE with TPT (35±28 [29–41] min versus 42±31 [38–46] min) ( p =0.052). A secondary analysis (36 patients) showed no change in LOS (273±125 [231–316] min versus 258±172 [234–282] min) but improved TPE with TPT (16±15 [11–21] min versus 42±31 [38–46] min) ( p <0.0001). Conclusions: TPT in the ED on a mobile platform was technically successful, well accepted by patients, and associated with a decrease in TPE but not LOS.

New onset diabetes after transplantation (NODAT) occurs less frequently in living donor liver transplant (LDLT) recipients than in deceased donor liver transplant (DDLT) recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75),P<0.001). Predictors for NODAT in LDLT recipients were hepatitis C (HCV) and treated acute cellular rejection (ACR). Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.

OBJECTIVE Identification of patients at high risk for new-onset diabetes after kidney transplantation (NODAT) will facilitate clinical trials for its prevention. RESEARCH DESIGN AND METHODS We previously described a pretransplant predictive risk model for NODAT using seven pretransplant variables (age, planned use of maintenance corticosteroids, prescription for gout medicine, BMI, fasting glucose, fasting triglycerides, and family history of diabetes). We have now applied the initial model to a cohort of 474 transplant recipients from another center for validation. We performed two analyses in the validation cohort. The first was a standard model with variables derived from the original study. The second was a summary score model, in which the sum of dichotomized variables (all the variables dichotomized at clinically relevant cut points) was used to categorize, individuals into low (0–1), intermediate (2, 3), or high (4–7) risk groups. We also conducted a combined database analyses, merging the initial and validation cohorts (n = 792) to obtain better estimates for a prediction equation. RESULTS Although the frequency of several risk factors differed significantly between the two cohorts, the models performed similarly in each cohort. Using the summary score model, incidences of NODAT in low-risk, medium-risk, and high-risk groups in the initial cohort were 12, 29, and 56%, and in the validation cohort incidences were 11, 29, and 51%. CONCLUSIONS A pretransplant model for NODAT, including many type 2 diabetes risk factors, predicted NODAT in the validation cohort.

Abstract Signaling through fibroblast growth factor receptor one (FGFR1) is a known inducer of proliferation in both embryonic and human adult mesenchymal stem cells (hMSCs) and positively regulates maintenance of stem cell viability. Leveraging the mitogenic potential of FGF2/FGFR1 signaling in stem cells for therapeutic applications necessitates a mechanistic understanding of how this receptor stimulates cell cycle progression. Using small interfering RNA (siRNA) depletion, antibody-inhibition, and small molecule inhibition, we establish that FGFR1 activity is rate limiting for self-renewal of hMSCs. We show that FGFR1 promotes stem cell proliferation through multiple mechanisms that unite to antagonize cyclin-dependent kinase (CDK) inhibitors. FGFR1 not only stimulates c-Myc to suppress transcription of the CDK inhibitors p21Waf1 and p27Kip1, thus promoting cell cycle progression but also increases the activity of protein kinase B (AKT) and the level of S-phase kinase-associated protein 2 (Skp2), resulting in the nuclear exclusion and reduction of p21Waf1. The in vivo importance of FGFR1 signaling for the control of proliferation in mesenchymal progenitor populations is underscored by defects in ventral mesoderm formation during development upon inhibition of its signaling. Collectively, these studies demonstrate that FGFR1 signaling mediates the continuation of MSC growth and establishes a receptor target for enhancing the expansion of mesenchymal progenitors while maintaining their multilineage potential. Stem Cells 2013;31:2724–2736

Quantifying the pathological features of flexor tendon pulleys is essential for grading the trigger finger since it provides clinicians with objective evidence derived from microscopic images. Although manual grading is time consuming and dependent on the observer experience, there is a lack of image processing methods for automatically extracting pulley pathological features. In this paper, we design and develop a color-based image segmentation system to extract the color and shape features from pulley microscopic images. Two parameters which are the size ratio of abnormal tissue regions and the number ratio of abnormal nuclei are estimated as the pathological progression indices. The automatic quantification results show clear discrimination among different levels of diseased pulley specimens which are prone to misjudgments for human visual inspection. The proposed system provides a reliable and automatic way to obtain pathological parameters instead of manual evaluation which is with intra- and interoperator variability. Experiments with 290 microscopic images from 29 pulley specimens show good correspondence with pathologist expectations. Hence, the proposed system has great potential for assisting clinical experts in routine histopathological examinations.

AbstractObjectivesPatient satisfaction is tied to outcome, but there is scant literature on the relationship of patient perceived outcome and attributes of the pain clinic visit, including the patient interaction with the pain management specialist. The primary purpose of this study is to identify attributes of the patient–provider interaction most strongly associated with patient perceived outcome of their clinic visit. The secondary aim is to correlate patient perceived outcome with patient self‐rated overall health.MethodsA patient satisfaction survey conducted via phone approximately 3 weeks after the patient's pain clinic visit.ResultsThe response rate was 60.2%; 987 patient surveys collected between 2006 and 2010 were used in the analysis. Four factors were significantly associated with the outcome: (1) Explanations by the physician of the patient's condition and treatment, (2) clear instructions regarding post‐appointment activities, (3) knowing the patient as a person, and (4) the patient's self‐rated health. In terms of the secondary objective, those who answered very good/excellent regarding their self‐rated health had an 87% increased odds of better (very good/excellent) outcome of their pain clinic visit (or 1.87 times the odds of better outcome) compared with those who answered poor/fair/good.ConclusionsOur results suggest that pain physicians may positively impact patient perceived outcomes of clinic visits by explaining the patient's condition and treatment, providing instructions, and taking the time to understand the patient and their values.

Abstract Metastasis, the leading cause of cancer death, requires tumor cell intravasation, migration through the bloodstream, arrest within capillaries, and extravasation to invade distant tissues. Few mechanistic details have been reported thus far regarding the extravasation process or re-entry of circulating tumor cells at metastatic sites. Here, we show that neuropilin-2 (NRP-2), a multifunctional nonkinase receptor for semaphorins, vascular endothelial growth factor (VEGF), and other growth factors, expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular extravasation and metastasis in zebrafish and murine xenograft models of clear cell renal cell carcinoma (RCC) and pancreatic adenocarcinoma. In tissue from patients with RCC, NRP-2 expression is positively correlated with tumor grade and is highest in metastatic tumors. In a prospectively acquired cohort of patients with pancreatic cancer, high NRP-2 expression cosegregated with poor prognosis. Through biochemical approaches as well as Atomic Force Microscopy (AFM), we describe a unique mechanism through which NRP-2 expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular adhesion and extravasation. Taken together, our studies reveal a clinically significant role of NRP-2 in cancer cell extravasation and promotion of metastasis. Cancer Res; 73(14); 4579–90. ©2013 AACR.