Gold Nanoparticles for Monitoring of Mesenchymal Stem-Cell-Loaded Bioresorbable Polymeric Wraps for Arteriovenous Fistula Maturation

Mesenchymal stem cell (MSC)-seeded polymeric perivascular wraps have been shown to enhance arteriovenous fistula (AVF) maturation. However, the wraps\u27 radiolucency makes their placement and integrity difficult to monitor. Through electrospinning, we infused gold nanoparticles (AuNPs) into polycaprolactone (PCL) wraps to improve their radiopacity and tested whether infusion affects the previously reported beneficial effects of the wraps on the AVF\u27s outflow vein. Sprague Dawley rat MSCs were seeded on the surface of the wraps. We then compared the effects of five AVF treatments-no perivascular wrap (i.e., control), PCL wrap, PCL + MSC wrap, PCL-Au wrap, and PCL-Au + MSC wrap-on AVF maturation in a Sprague Dawley rat model of chronic kidney disease (n = 3 per group). Via micro-CT, AuNP-infused wraps demonstrated a significantly higher radiopacity compared to that of the wraps without AuNPs. Wraps with and without AuNPs equally reduced vascular stenoses, as seen via ultrasonography and histomorphometry. In the immunofluorescence analysis, representative MSC-seeded wraps demonstrated reduced neointimal staining for markers of infiltration with smooth muscle cells (α-SMA), inflammatory cells (CD45), and fibroblasts (vimentin) compared to that of the control and wraps without MSCs. In conclusion, AuNP infusion allows in vivo monitoring via micro-CT of MSC-seeded polymeric wraps over time, without compromising the benefits of the wrap for AVF maturation

An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer

Background: Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease. Methods: We investigated urinary samples (n ¼ 121) from patients with bladder cancer (n ¼ 68) and age-matched controls (n ¼ 53). Fifteen miRs were quantified using real-time PCR. Results: We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs 15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA Po0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance). Conclusion: The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed

Assessment of Health Care Cost for Complex Surgical Patients: Review of Cost, Re-Imbursement and Revenue Involved in Pancreatic Surgery at a High-Volume Academic Medical Centre

AbstractBackgroundPancreatic surgery is complex with the potential for costly hospitalization.MethodsA retrospective review of patients undergoing a pancreatic resection was performed.ResultsThe median age of the study population was 64 years. Half of the cohort was female (51%), and the majority were white (62%). Most patients underwent a pancreaticoduodenectomy (PD) (69%). The pre-operative age-adjusted Charlson comorbidity index was zero for 36% (n = 50), 1 for 31% (n = 43) and ≥2 for 33% (n = 45). The Clavien–Dindo grading system for post-operative complication was grade I in 17% (n = 24), whereas 45% (n = 62) were higher grades. The medians direct fixed, direct variable, fixed indirect and total costs were $2476,$15 397, $13 207 and$31 631, respectively. There was a positive contribution margin of $7108, whereas the net margin was a loss of$6790. On univariate analyses, age, type of operation and complication grade were associated with total cost (P ≤ 0.05), whereas operation type and complication grade were associated with a net margin (P = 0.01). These findings remained significant on multivariate analysis (P < 0.05).ConclusionsIncreased cost, reimbursement and revenue were associated with type of operation and post-operative complications

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury

This research was performed as a project of the Intestinal Stem Cell Consortium, a collaborative research project funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIH U01 DK-085508 to CWH), and a grant from Oklahoma Center for the Advancement of Science and Technology to CWH.Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.Yeshttp://www.plosone.org/static/editorial#pee

Minimally invasive image-guided therapies for hepatocellular carcinoma

Mohamed E Abdelsalam,1 Ravi Murthy,1 Rony Avritscher,1 Armeen Mahvash,1 Michael J Wallace,1 Ahmed O Kaseb,2 Bruno C Odisio,1 1Department of Interventional Radiology, 2Department of Medical Oncology, The University of Texas MD&nbsp;Anderson Cancer Center, Houston, TX, USA Abstract: Hepatocellular carcinoma (HCC) is the fifth most frequently occurring cancer globally and predominantly develops in the setting of various grades of underlying chronic liver disease, which affects management decisions. Image-guided percutaneous ablative or transarterial therapies have acquired wide acceptance in HCC management as a single treatment modality or combined with other treatment options in patients who are not amenable for surgery. Recently, such treatment modalities have also been used for bridging or downsizing before definitive treatment (ie, surgical resection or liver transplantation). This review focuses on the use of minimally invasive image-guided locoregional therapies for HCC. Additionally, it highlights recent advancements in imaging and catheter technology, embolic materials, chemotherapeutic agents, and delivery techniques; all lead to improved patient outcomes, thereby increasing the interest in these invasive techniques. Keywords: hepatocelleular carcinoma, locoregional therapy, TACE, ablation, 90