We developed a chondroitin sulfate - polyethylene glycol (CS-PEG) adhesive hydrogel with numerous potential biomedical applications. The carboxyl groups on chondroitin sulfate (CS) chains were functionalized with N-hydroxysuccinimide (NHS) to yield chondroitin sulfate succinimidyl succinate (CS-NHS). Following purification, the CS-NHS molecule can react with primary amines to form amide bonds. Hence, using six arm polyethylene glycol amine PEG-(NH2)6 as a crosslinker we formed a hydrogel which was covalently bound to proteins in tissue via amide bonds. By varying the initial pH of the precursor solutions, the hydrogel stiffness, swelling properties, and kinetics of gelation could be controlled. The sealing/adhesive strength could also be modified by varying the damping and storage modulus properties of the material. The adhesive strength of the material with cartilage tissue was shown to be ten times higher than that of fibrin glue. Cells encapsulated or in direct contact with the material remained viable and metabolically active. Furthermore, CS-PEG material produced minimal inflammatory response when implanted subcutaneously in a rat model and enzymatic degradation was demonstrated in vitro. This work establishes an adhesive hydrogel derived from biological and synthetic components with potential application in wound healing and regenerative medicine.

Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

Soft tissue reconstruction often requires multiple surgical procedures that can result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical challenge because even subtle deformities can severely affect an individual’s social and psychological function. We therefore developed a biosynthetic soft tissue replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be injected and photocrosslinked in situ with transdermal light exposure. Modulating the ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a dose-dependent relationship between increasing PEG concentration and enhanced implant volume persistence. In direct comparison with commercial HA injections, the PEG-HA implants maintained significantly greater average volumes and heights. Reversibility of the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in human patients confirmed the feasibility of the transdermal photocrosslinking approach for implantation in abdomen soft tissue, although an inflammatory response was observed surrounding some of the materials.

Background Soft tissue repair is currently limited by the availability of autologous tissue sources and the absence of an ideal soft tissue replacement comparable to native adipose tissue. Extracellular matrix (ECM)-based biomaterials have demonstrated great potential as instructive scaffolds for regenerative medicine, mechanically and biochemically defined by the tissue of origin. As such, the distinctive high lipid content of adipose tissue requires unique processing conditions to generate a biocompatible scaffold for soft tissue repair. Methods Human adipose tissue was decellularized to obtain a matrix devoid of lipids and cells, while preserving ECM architecture and bioactivity. To control degradation and volume persistence, the scaffold was crosslinked using hexamethylene diisocyanate and 1-Ethyl-3-(-3-dimethylaminopropyl) carbodiimide. In vitro studies with human adipose-derived stem cells were used to assess cell viability and adipogenic differentiation on the biomaterial. In vivo biocompatibility and volume persistence were evaluated by subcutaneous implantation over 12 weeks in a small animal model. Results The scaffold provided a biocompatible matrix supporting the growth and differentiation of adipose-derived stem cells in vitro. Crosslinking the matrix increased its resistance to enzymatic degradation. Subcutaneous implantation of the acellular adipose matrix in Sprague-Dawley rats showed minimal inflammatory reaction. Adipose tissue development and vascularization was observed in the implant, with host cells migrating into the matrix indicating the instructive potential of the matrix for guiding tissue remodeling and regeneration. Conclusions With its unique biological and mechanical properties, decellularized adipose ECM is a promising biomaterial scaffold that can potentially be used allogenically for the correction of soft tissue defects.

Combined PET/CT fusion scanning was most useful in the detection and management of recurrent papillary thyroid cancer in patients who had average thyroglobulin levels greater than 10 ng/mL and when the tumor no longer concentrated radioactive iodine. In 100% of the cases in which PET/CT localized a region suspicious for malignancy, histopathological analysis confirmed the results. When PET/CT is positive, it is a powerful tool for predicting exact locations of recurrent papillary thyroid cancer, thus making it a reliable guide for surgical planning. PET/CT is a supplement to conventional imaging and fine-needle aspiration in the workup of recurrent papillary thyroid cancer. A negative finding on PET/CT is not sufficiently reliable to preclude further investigation and treatment.

To describe the clinical presentation and the radiological and surgical findings in patients with spontaneous meningoencephalocele of the temporal bone. Design: Retrospective case series. Setting: Academic, tertiary care medical center. Patients: Fifteen consecutive patients with surgically confirmed meningoencephalocele of the mastoid and middle ear, without a history of trauma, tumor, cholesteatoma, or surgery of the mastoid or cranium, who were treated at our institution between January 1, 1999, and December 31, 2006. Results: Ten of the 15 patients were women. Ages ranged from 31 to 77 years, with 12 patients 50 years or older. The most common presenting complaint was newonset hearing loss in 14 patients, followed by aural fullness and headache. Cerebrospinal fluid formed an effusion in the middle ears of 13 patients and was most commonly identified when myringotomy resulted in continuous clear otorrhea. Four subjects had a history of adult-onset recurrent acute otitis media with intermittent otorrhea, which in 1 case was complicated by brain abscess. At least 1 full-thickness defect of the tegmen associated with cortical thinning of the middle fossa floor was identified in all cases on high-resolution computed tomography. At surgery, herniations of meningeal and cerebral tissue were seen through 1 (7 cases) or 2 (8 cases) defects in the middle fossa floor. Obstruction of antral aeration by the meningoencephalocele was present in all 4 cases associated with otitis media.

Patients with a positive serum calcium slope (t = 6 and 12 hours) after total thyroidectomy are safe to discharge within 24 hours after surgery with patient education with or without calcium supplementation. In addition, patients with a nonpositive slope and a serum calcium level > or =8 mg/dL at 12 hours postoperatively (< or =0.5 mg/dL below the low end of normal) are unlikely to develop significant hypocalcemia, especially beyond 24 hours postoperatively, and therefore can be safely discharged within 24 hours after total thyroidectomy with patient education and oral calcium supplementation. Our management algorithm identifies those patients at low risk of developing significant hypocalcemia early in the postoperative course after total thyroidectomy to allow for a short hospital stay and safe discharge.

This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.