Wesley N. Sivak

Assessing the impact of antibiotic prophylaxis in outpatient elective hand surgery: A single-center, retrospective review of 8,850 cases

PURPOSE Prophylactic antibiotics have been shown to prevent surgical site infection (SSI) after some gastrointestinal, orthopedic, and plastic surgical procedures, but their efficacy in clean, elective hand surgery is unclear. Our aims were to assess the efficacy of preoperative antibiotics in preventing SSI after clean, elective hand surgery, and to identify potential risk factors for SSI. METHODS We queried the database from an outpatient surgical center by Current Procedural Terminology code to identify patients who underwent elective hand surgery. For each medical record, we collected patient demographics and characteristics along with preoperative, intraoperative, and postoperative management details. The primary outcome of this study was SSI, and secondary outcomes were wound dehiscence and suture granuloma. RESULTS From October 2000 through October 2008, 8,850 patient records met our inclusion criteria. The overall SSI rate was 0.35%, with an average patient follow-up duration of 79 days. The SSI rates did not significantly differ between patients receiving antibiotics (0.54%; 2,755 patients) and those who did not (0.26%; 6,095 patients). Surgical site infection was associated with smoking status, diabetes mellitus, and longer procedure length irrespective of antibiotic use. Subgroup analysis revealed that prophylactic antibiotics did not prevent SSI in male patients, smokers, or diabetics, or for procedure length less than 30 minutes, 30 to 60 minutes, and greater than 60 minutes. CONCLUSIONS Prophylactic antibiotic administration does not reduce the incidence of SSI after clean, elective hand surgery in an outpatient population. Moreover, subgroup analysis revealed that prophylactic antibiotics did not reduce the frequency of SSI among patients who were found to be at higher risk in this study. We identified 3 factors associated with the development of SSI in our study: diabetes mellitus status, procedure length, and smoking status. Given the potential harmful complications associated with antibiotic use and the lack of evidence that prophylactic antibiotics prevent SSIs, we conclude that antibiotics should not be routinely administered to patients who undergo clean, elective hand surgery. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic III.

Spatially controlled delivery of neurotrophic factors in silk fibroin-based nerve conduits for peripheral nerve repair.

Restoration with sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Silk has shown clinical promise for numerous tissue engineering applications due to its biocompatibility, impressive mechanical properties, and Food and Drug Administration approval. The aim of this study was to evaluate the efficacy of silk fibroin–based nerve guides containing glial cell line-derived neurotrophic factor (GDNF) in a long-gap sized (15 mm) rat sciatic nerve defect model. Four groups of nerve conduits were prepared: (1) silk conduits with empty silk microspheres, (2) silk conduits with GDNF-loaded silk microspheres uniformly distributed in the conduit wall, (3) silk conduits with GDNF-loaded silk microspheres in a controlled manner with the highest GDNF concentration at the distal end, and (4) isograft. After 6 weeks, the nerve grafts were explanted, harvested, and fixed for histologic analysis. Nerve tissue stained with the S-100, and neuroendocrine marker PGP 9.5 antibodies demonstrated a significantly increased density of nerve tissue in the GDNF-treated groups compared with the empty microsphere (control) group (P < 0.05). GDNF-treated animals with a higher concentration of GDNF in the distal portion possessed a significantly higher density of PGP 9.5 protein middle conduit part than comparison to GDNF uniform-treated animals (P < 0.05). Silk-based nerve conduits possess optimal mechanical and degradative properties, rendering them potentially useful in peripheral nerve repair. This study demonstrates that novel, porous silk fibroin–based nerve conduits, infused with GDNF in a controlled manner, represent a potentially viable conduit for Schwann cell migration and proliferation in the regeneration of peripheral nerves.

Simultaneous drug release at different rates from biodegradable polyurethane foams

In this study, we present an approach for the simultaneous release of multiple drug compounds at different rates from single-phase polyurethane foams constructed from lysine diisocyanate (LDI) and glycerol. The anti-cancer compounds DB-67 and doxorubicin were covalently incorporated into polyurethane foams, whereby drug release can then occur in concert with material degradation. To begin, the reactions of DB-67 and doxorubicin with LDI in the presence of a tertiary amine catalyst were monitored with infrared spectroscopy; each compound formed urethane linkages with LDI. Fluorescent spectra of DB-67 and doxorubicin were then recorded in phosphate-buffered saline, pH 7.4 (PBS), to ensure that each anti-cancer compound could be quantitatively detected alone and in combination. Doxorubicin and DB-67 were then incorporated into a series of degradable LDI-glycerol polyurethane foams alone and in combination with one another. The sol content, average porosity and drug distribution throughout each foam sample was measured and found to be similar amongst all foam samples. The stability of DB-67 and doxorubicins fluorescent signal was then assessed over a 2-week period at 70 degrees C. Release rates of the compounds from the foams were assessed over a 10-week period at 4, 22, 37 and 70 degrees C by way of fluorescence spectroscopy. Release was found to be temperature-dependent, with rates related to the chemical structure of the incorporated drug. This study demonstrates that differential release of covalently bound drugs is possible from simple single-phase, degradable polyurethane foams.

LDI-glycerol polyurethane implants exhibit controlled release of DB-67 and anti-tumor activity in vitro against malignant gliomas.

The purpose of the present study was to develop a biodegradable and biocompatible polyurethane drug delivery system based on lysine diisocyanate (LDI) and glycerol for the controlled release of 7-tert-butyldimethylsilyl-10-hydroxy-camptothecin (DB-67). DB-67 has yet to be implemented in any clinical therapies due to the inability to delivered it in sufficient quantities to impact tumor growth and disease progression. To remedy this, DB-67 was covalently incorporated into our delivery system by way of an organometallic urethane catalyst and was found to be dispersed evenly throughout the LDI-glycerol polyurethane discs. Scanning electron micrographs indicate that the LDI-glycerol discs are uniform and possess a pore distribution typical of the non-solvent casting technique used to prepare them. The release rates of DB-67 from the LDI-glycerol discs were found to vary with both time and temperature and were shown capable of delivering therapeutic concentrations of DB-67 in vitro. Cellular proliferation assays demonstrate that empty LDI-glycerol discs alone do not significantly alter the growth of malignant human glioma cell lines (U87, T98G, LN229 and SG388). DB-67-loaded LDI-glycerol polyurethane discs were found to inhibit cellular proliferation by 50% on average in all the malignant glioma cell lines tested. These results clearly demonstrate the long-term, slow release of DB-67 from LDI-glycerol polyurethane discs and their potential for postoperative intracranial chemotherapy of cancers.

Incorporation of ionic ligands accelerates drug release from LDI-glycerol polyurethanes.

This study seeks to determine the effect of ionic ligands on the drug delivery characteristics of biodegradable polyurethane materials synthesized from lysine diisocyanate (LDI) and glycerol. Two naturally occurring, structurally related ionic species, choline chloride (CC) and isethionic acid (ISE), along with 3,3-dimethyl-butanol (DMB), their neutral carbon analog, were covalently incorporated into LDI-glycerol polyurethane materials. Selected organometallic and tertiary amine catalysts were used to fashion films and foams, respectively. The potent anticancer compound DB-67, a fluorescent camptothecin derivative, was also covalently linked to the polyurethane constructs. It was first determined that the sulfonate functional group on ISE does not react to a significant degree with isocyanate. The morphological characteristics of the polyurethane films and foams were assessed via scanning electron microscopy, showing significant differences related to the ionic ligands. The ionic materials displayed increased swelling in aqueous media over the neutral control materials. Differences in the distribution of DB-67 throughout the films and foams were then detected by fluorescence microscopy. The drug delivery characteristics of the materials were then evaluated in vitro, revealing accelerated release from ionic materials. The results of this study demonstrate the unique effects that incorporation of ionic ligands into LDI-glycerol polyurethanes have on the morphology and drug distribution of the materials. These differences have a significant impact on the drug delivery characteristics of the materials, and this information should prove useful in the design and synthesis of biodegradable controlled release systems.

Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration.

Nerve conduits are a proven strategy for guiding axon regrowth following injury. This study compares degradable silk–trehalose films containing chondroitinase ABC (ChABC) and/or glial cell line‐derived neurotrophic factor (GDNF) loaded within a silk fibroin‐based nerve conduit in a rat sciatic nerve defect model. Four groups of silk conduits were prepared, with the following silk–trehalose films inserted into the conduit: (a) empty; (b) 1 µg GDNF; (3) 2 U ChABC; and (4) 1 µg GDNF/2 U ChABC. Drug release studies demonstrated 20% recovery of GDNF and ChABC at 6 weeks and 24 h, respectively. Six conduits of each type were implanted into 15 mm sciatic nerve defects in Lewis rats; conduits were explanted for histological analysis at 6 weeks. Tissues stained with Schwann cell S‐100 antibody demonstrated an increased density of cells in both GDNF‐ and ChABC‐treated groups compared to empty control conduits (p < 0.05). Conduits loaded with GDNF and ChABC also demonstrated higher levels of neuron‐specific PGP 9.5 protein when compared to controls (p < 0.05). In this study we demonstrated a method to enhance Schwann cell migration and proliferation and also foster axonal regeneration when repairing peripheral nerve gap defects. Silk fibroin‐based nerve conduits possess favourable mechanical and degradative properties and are further enhanced when loaded with ChABC and GDNF. Copyright

Management of failed alveolar bone grafts: improved outcomes and decreased morbidity with allograft alone.

Background: This study demonstrates the safety and efficacy of allograft alone in revision alveolar bone graft surgery. Methods: A retrospective review of the authors’ institution’s alveolar bone graft experience (from 2004 to 2012) with open iliac crest bone graft, minimal-access iliac crest bone graft plus supplemental allograft, and revision allograft alone was performed. All patients (n = 47) were treated with alveolar fistula repair with primary closure. Results: Group 1 patients (12 male, 10 female; average age, 10 years) received iliac crest bone graft alone; 17 had unilateral and five had bilateral clefts. Group 2 (eight male, six female; average age, 9 years) received an iliac crest bone graft plus allograft; six clefts were unilateral and eight were bilateral. Group 3 (six male, five female; average age, 13 years) received revision allograft alone; seven clefts were unilateral and four were bilateral. Average operative time/alveolus was shortest in group 3 compared with groups 1 and 2 (p < 0.0005). Average engraftment was better in group 3 than in group 1 (p < 0.001) and similar to that in group 2 (p < 0.079). Revision alveolar bone graft with allograft alone improved Enemark scores from 3.7 preoperatively to 1.0 postoperatively (p < 0.0001). Hospital stay was shortest in group 3 compared with groups 1 and 2 (p < 0.0001). Bone graft extrusion occurred in six patients (27.3 percent) in group 1, no complications occurred in group 2, and a single necrotic central incisor was lost at the time of revision bone grafting in group 3 (9.1 percent). Conclusion: Allograft alone is safe and effective and provides a reliable alternative when traditional alveolar bone graft with iliac crest bone graft has failed. CLINICAL QUESTIONS/LEVEL OF EVIDENCE: Therapeutic, III.

The Role of Chondroitinase as an Adjuvant to Peripheral Nerve Repair

Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of neural regeneration in the peripheral nervous system. Following nerve injury, inhibitory CSPGs accumulate within the endoneurium and Schwann cell basal lamina of the distal nerve stump. The utilization of chondroitinase ABC (chABC) has led to a marked increase in the ability of injured axons to regenerate across gaps through the CSPG-laden extracellular matrix. Experimental models have repeatedly shown chABC to be capable of degrading the CSPGs that hinder neurite outgrowth. In this article, the characterization of CSPGs, their upregulation following peripheral nerve injury, and potential mechanisms behind their growth and inhibition are described. To date, the literature supports that the adjunct use of chABC may be beneficial to peripheral nerve repair in digesting inhibitory CSPGs. chABC has also shown some indication of synergism with other therapies, such as stem cell transplantation. Evidence supporting the use of chondroitinase as a treatment modality in nerve repair, either alone or in combination with other agents, is reviewed within. Finally, several shortcomings of chABC are addressed, notably its thermal stability and physiologic longevity - both hindering its widespread clinical adoption. Future studies are warranted in order to optimize the therapeutic benefits of the chondroitinase enzyme.

Polymeric biomaterials for nerve regeneration: fabrication and implantation of a biodegradable nerve guide.

Optimizing the quantity, quality, and speed of axon regeneration is important in maximizing functional outcomes following peripheral nerve injury. When severed, injured nerves must be able to regenerate and reconnect to the structures they previously controlled within 12-18 months before sensation and motion are permanently lost. Nerve sprouts from the proximal stump will spontaneously migrate toward the distal stump in the event of a nerve transection. However, surgical intervention remains necessary to repair transection injuries. Regeneration becomes particularly troublesome with large gaps, where autologous nerve grafts or nerve guides are used to repair transected nerves. Nerve conduits function as therapeutic adjuncts, guiding axonal regeneration across gap defects. Despite the availability of several FDA-approved nerve conduits, functional outcomes following their use remain less than optimal. Much work has been focused on developing nerve conduits to improve peripheral nerve repair outcomes. This chapter describes fabrication of a poly(caprolactone) nerve guide and demonstrates its use in a rat sciatic nerve model.

Diagnosis of Ulnar Nerve Entrapment at the Arcade of Struthers with Electromyography and Ultrasound

Summary: Ulnar neuropathy is caused by compression of the ulnar nerve in the upper extremity, frequently occurring at the level of the elbow or wrist. Rarely, ulnar nerve entrapment may be seen proximal to the elbow. This report details a case of ulnar neuropathy diagnosed and localized to the arcade of Struthers with electromyography (EMG) and ultrasound (US) imaging and confirmed at time of operative release. US imaging and EMG findings were used to preoperatively localize the level of compression in a patient presenting with left ulnar neuropathy. In this case, ulnar entrapment 8 cm proximal to the medial epicondyle was diagnosed. Surgical release was performed and verified the level of entrapment at the arcade of Struthers in the upper arm. Alleviation of symptoms was noted at 8-week follow-up; no complications occurred. US imaging can be used in complement with EMG studies to properly diagnose and localize the level of ulnar nerve entrapment. This facilitates full release of the nerve and may prevent the need for revision surgery.