Making a Painless Drain: Proof of Concept.

Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%). Glutaraldehyde (1%) was added to crosslink the gelatin into a hydrogel. The hydrogel was dehydrated, resulting in a thin, stable polymer. Sterile lidocaine hydrogel-coated silicone discs and control discs were prepared and surgically implanted in the subcutaneous space of C57B6 mice. Using von Frey filaments, mice underwent preoperative baseline pain testing, followed by pain testing on post-procedure day 1 and 3. On post-procedure day 1, mice implanted with control discs demonstrated no change in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 2.4-fold (P = 0.36) and 4.7-fold (P = 0.01) increase in pain tolerance, respectively. On post-procedure day 3, mice implanted with control discs demonstrated a 0.7-fold decrease in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 1.8-fold (P = 0.88) and 8.4-fold (P = 0.02) increase in pain tolerance, respectively. Our results demonstrate successful development of a lidocaine-eluting chest tube with hydrogel coating, leading to improved pain tolerance in vivo. The concept of a drug-eluting drain coating has significant importance due to its potential universal application in a variety of drain types and insertion locations.

Sulfonated Thermoresponsive Injectable Gel for Sequential Release of Therapeutic Proteins to Protect Cardiac Function after Myocardial Infarction.

Myocardial infarction causes cardiomyocyte death and persistent inflammatory responses, which generate adverse pathological remodeling. Delivering therapeutic proteins from injectable materials in a controlled-release manner may present an effective biomedical approach for treating this disease. A thermoresponsive injectable gel composed of chitosan, conjugated with poly(N-isopropylacrylamide) and sulfonate groups, was developed for spatiotemporal protein delivery to protect cardiac function after myocardial infarction. The thermoresponsive gel delivered vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and platelet-derived growth factor (PDGF) in a sequential and sustained manner in vitro. An acute myocardial infarction mouse model was used to evaluate polymer biocompatibility and to determine therapeutic effects from the delivery system on cardiac function. Immunohistochemistry showed biocompatibility of the hydrogel, while the controlled delivery of the proteins reduced macrophage infiltration and increased vascularization. Echocardiography showed an improvement in ejection fraction and fractional shortening after injecting the thermal gel and proteins. A factorial design of experimental study was implemented to optimize the delivery system for the best combination and doses of proteins for further increasing stable vascularization and reducing inflammation using a subcutaneous injection mouse model. The results showed that VEGF, IL-10, and FGF-2 demonstrated significant contributions toward promoting long-term vascularization, while PDGF's effect was minimal.

iHear: Canadian medical student based hearing assessment program for grade school children using a tablet audiometer.

PURPOSE: To evaluate the progress and challenges of a hearing screening program as well as review the incidence of pediatric hearing loss in grade school children participating in this program. METHODS: Medical students from the University of Ottawa established iHear, a grade school hearing assessment program that uses novel tablet audiometry. Over 3 years, children in grades 1 and 2 were assessed and those found to have abnormal results on iHear assessment were then referred to audiology for formal testing, and to otolaryngology if needed. RESULTS: From 2014 to 2017, 753 children aged 5-9 years old were assessed for hearing loss. Mean age of participants was 6.7 years, 51.9% of whom were female. Of the children assessed, 86 (11.4%) had abnormal results and 6 (0.8%) had inconsistent results, necessitating 92 referrals for assessment by a professional audiologist. Of the 65 participants who completed secondary audiologic assessment, 54 (83.1%) were normal and 11 (16.9%) had a definitive hearing loss or abnormal tympanometry. A total of 32 children were lost to follow-up. A total of 118 medical students were involved in the iHear program. CONCLUSIONS: Hearing loss in grade school populations continues to go undetected across Canada. Programs such as iHear demonstrate that gaps in the provision of hearing assessment can be filled effectively by medical students equipped with tablet audiometry. Medical student exposure to audiology and otolaryngology increased through the iHear program.

Injectable Polymeric Delivery System for Spatiotemporal and Sequential Release of Therapeutic Proteins To Promote Therapeutic Angiogenesis and Reduce Inflammation.

Myocardial infarction (MI) causes cardiac cell death, induces persistent inflammatory responses, and generates harmful pathological remodeling, which leads to heart failure. Biomedical approaches to restore blood supply to ischemic myocardium, via controlled delivery of angiogenic and immunoregulatory proteins, may present an efficient treatment option for coronary artery disease (CAD). Vascular endothelial growth factor (VEGF) is necessary to initiate neovessel formation, while platelet-derived growth factor (PDGF) is needed later to recruit pericytes, which stabilizes new vessels. Anti-inflammatory cytokines like interleukin-10 (IL-10) can help optimize cardiac repair and limit the damaging effects of inflammation following MI. To meet these angiogenic and anti-inflammatory needs, an injectable polymeric delivery system composed of encapsulating micelle nanoparticles embedded in a sulfonated reverse thermal gel was developed. The sulfonate groups on the thermal gel electrostatically bind to VEGF and IL-10, and their specific binding affinities control their release rates, while PDGF-loaded micelles are embedded in the gel to provide the sequential release of the growth factors. An in vitro release study was performed, which demonstrated the sequential release capabilities of the delivery system. The ability of the delivery system to induce new blood vessel formation was analyzed in vivo using a subcutaneous injection mouse model. Histological assessment was used to quantify blood vessel formation and an inflammatory response, which showed that the polymeric delivery system significantly increased functional and mature vessel formation while reducing inflammation. Overall, the results demonstrate the effective delivery of therapeutic proteins to promote angiogenesis and limit inflammatory responses.

A sulfonated reversible thermal gel for the spatiotemporal control of VEGF delivery to promote therapeutic angiogenesis.

Despite medical and surgical advancements for the treatment of cardiovascular disease, mortality and morbidity remain high. Therapeutic angiogenesis has been one approach to address the major clinical need for a more effective treatment to restoring blood flow in ischemic organs and tissues, but current progress in angiogenic drug delivery is inadequate at providing sufficient bioavailability without causing safety concerns. An injectable sulfonated reversible thermal gel composed of a polyurea conjugated with poly(N-isopropylacrylamide) and sulfonate groups has been developed for the delivery of angiogenic factors. The thermal gel allowed for the spatiotemporal control of vascular endothelial growth factor release with a decreased initial burst release and reduced release rate in vitro. A subcutaneous injection mouse model was used to evaluate efficacious vascularization and assess the inflammatory response due to a foreign body. Thermal gel injections showed substantial vascularization properties by inducing vessel formation, recruitment and differentiation of vascular endothelial cells, and vessel stabilization by perivascular cells, while infiltrating macrophages due to the thermal gel injections decreased over time. These results demonstrated effective localization and delivery of angiogenic factors for therapeutic angiogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3053-3064, 2018.

Clinical and pathologic factors of prognostic significance in penile squamous cell carcinoma in a North American population.

OBJECTIVE: To analyze, in a clinicopathologic correlation study, a small population of primarily white men with invasive squamous cell carcinoma of the penis for potential prognostic predictors. Penile squamous cell carcinoma is an uncommon cancer in North America. It has a wide spectrum of clinical behavior and an understudied pathogenesis. METHODS: The data from 43 patients with invasive squamous cell carcinoma of the penis were studied retrospectively. Extensive chart reviews were conducted, glass slides were reviewed, and tissue microarrays were constructed for analysis of immunohistochemical stains p16(INK4a), p53, and Ki-67. Univariate and multivariate logistic regression analyses were performed to elucidate any clinical or pathologic factors that would predict overall survival. RESULTS: The mean age at diagnosis was 63 years. Most cases (63%) were invasive squamous cell carcinoma, not otherwise specified, and presented as pathologic stage T1 or T2 tumors. Of the 43 patients, 23% died of their disease; 53% of the cases stained for p16(INK4a). Higher pathologic tumor stage and a lack of p16(INK4a) staining were independent predictors of worse overall survival (P = .014) and cancer-specific survival (P = .010). CONCLUSION: Our results have shown that 53% of the invasive penile squamous cell carcinoma cases in this population were associated with human papillomavirus, using p16(INK4a) as a surrogate marker of human papillomavirus infection. These patients had a statistically significant survival advantage, independent of other prognostic factors.