Kevin W. Sexton

Women in Academic Surgery: The Pipeline Is Busted

PURPOSE This investigation examined the trends for gender-based advancement in academic surgery by performing a comparative analysis of the rate of change in the percentage of medical students, surgery residents, and full professors of surgery who are women. METHODS All available Women in Medicine Annual Reports were obtained from the American Association of Medical Colleges (AAMC). The gender compositions of medical graduates, surgery residents, and full professors were plotted. Binomial and linear trendlines were calculated to estimate the year when 50% of surgery full professors would be women. Additionally, the percentage distribution of men and women at each professorial rank was determined from 1995 to 2009 using these reports to demonstrate the rate of academic advancement of each gender. RESULTS The slope of the line of increase for women full professors is significantly less than for female medical students and for female general surgery residents (0.36, compared with 0.75 and 0.99, respectively). This predicts that the earliest time that females will account for 50% of full professors in surgery is the year 2096. When comparing women and men in academic ranks, we find that women are much less likely than men to be full professors. CONCLUSIONS The percentage of full professors in surgery who are women is increasing at a rate disproportionately slower than the increases in female medical students and surgery residents. The rates of increase in female medical students and surgery residents are similar. The disproportionately slow rate of increase in the number of female full professors suggests that multiple factors may be responsible for this discrepancy.

Preoperative anemia predicts thrombosis and free flap failure in microvascular reconstruction.

AbstractPatients undergoing microvascular reconstruction are often anemic from a combination of iatrogenic hemodilution and acute blood losses. No major clinical study describes the impact of preoperative anemia on free flap morbidity. The plastic surgery service at a high-volume academic center performed 156 free flaps among 147 patients from December 2005 to December 2010. One hundred thirty-two had a preoperative hemoglobin (Hb) or hematocrit (Hct), with mean values of 11.8 ± 2.4 g/dL and 35.2% ± 7.0%, respectively. The overall failure rate was 9% (12/132), primarily from vascular thrombosis (6/12). Through logistic regression analysis, Hb and Hct were significant predictors of flap failure (P < 0.005) and vascular thrombosis (P < 0.05). Fisher exact test revealed a significant increase in failure risk at Hct level less than 30% (Hb < 10 g/dL) (relative risk, 4.76, P = 0.006), and probit analysis demonstrated an exposure-response relationship to decreased Hct level (P < 0.005). These findings support that preoperative anemia could significantly impact free flap morbidity.

Hydrophilic polymers enhance early functional outcomes after nerve autografting.

BACKGROUND Approximately 12% of operations for traumatic neuropathy are for patients with segmental nerve loss, and less than 50% of these injuries obtain meaningful functional recovery. Polyethylene glycol (PEG) therapy has been shown to improve functional outcomes after nerve severance, and we hypothesized this therapy could also benefit nerve autografting. METHODS We used a segmental rat sciatic nerve injury model in which we repaired a 0.5-cm defect with an autograft using microsurgery. We treated experimental animals with solutions containing methylene blue (MB) and PEG; control animals did not receive PEG. We recorded compound action potentials (CAPs) before nerve transection, after solution therapy, and at 72 h postoperatively. The animals underwent behavioral testing at 24 and 72 h postoperatively. After we euthanized the animals, we fixed the nerves, sectioned and immunostained them to allow for quantitative morphometric analysis. RESULTS The introduction of hydrophilic polymers greatly improved morphological and functional recovery of rat sciatic axons at 1-3 d after nerve autografting. Polyethylene glycol therapy restored CAPs in all animals, and CAPs were still present 72 h postoperatively. No CAPS were detectable in control animals. Foot Fault asymmetry scores and sciatic functional index scores were significantly improved for PEG therapy group at all time points (P < 0.05 and P < 0.001; P < 0.001 and P < 0.01). Sensory and motor axon counts were increased distally in nerves treated with PEG compared with control (P = 0.019 and P = 0.003). CONCLUSIONS Polyethylene glycol therapy improves early physiologic function, behavioral outcomes, and distal axonal density after nerve autografting.

Dual-imaging system for burn depth diagnosis

Currently, determination of burn depth and healing outcomes has been limited to subjective assessment or a single modality, e.g., laser Doppler imaging. Such measures have proven less than ideal. Recent developments in other non-contact technologies such as optical coherence tomography (OCT) and pulse speckle imaging (PSI) offer the promise that an intelligent fusion of information across these modalities can improve visualization of burn regions thereby increasing the sensitivity of the diagnosis. In this work, we combined OCT and PSI images to classify the degree of burn (superficial, partial-thickness and full-thickness burns). Algorithms were developed to integrate and visualize skin structure (with and without burns) from the two modalities. We have completed the proposed initiatives by employing a porcine burn model and compiled results that attest to the utility of our proposed dual-modal fusion approach. Computer-derived data indicating the varying burn depths were validated through immunohistochemical analysis performed on burned skin tissue. The combined performance of OCT and PSI modalities provided an overall ROC-AUC=0.87 (significant at p<0.001) in classifying different burn types measured after 1-h of creating the burn wounds. Porcine model studies to assess feasibility of this dual-imaging system for wound tracking are underway.

Lack of emergency hand surgery: discrepancy between elective and emergency hand care.

Wrist, hand, and finger trauma are the most common injuries presenting to emergency departments. Shortage of emergency hand care is an emerging problem, as on-call hand coverage declines. This study evaluates the availability of elective and emergency hand surgery services in Tennessee, with the use of telephone surveys administered to emergency department and operating facility management. One hundred eleven Tennessee hospitals completed the surveys (93% response rate). In all, 77% of hospitals offer elective hand surgery, 58% offer basic emergency hand services, 18% offer occasional hand specialist call coverage and only 7% of hospitals have 24/7 hand specialist call coverage. Hospitals with hand specialists have significantly more payer charges from commercial insurance than hospitals without hand specialists (26.1% vs. 16.1%, P < 0.001). Our results strongly support the need for increased emergency hand coverage. Solutions include creating multihospital coordinated call schedules, increasing incentives for call coverage, and training more hand specialists.

4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury.

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.

Use of Brilliant Blue FCF during vein graft preparation inhibits intimal hyperplasia

BACKGROUND Intimal hyperplasia remains the primary cause of vein graft failure for the 1 million yearly bypass procedures performed using human saphenous vein (HSV) grafts. This response to injury is caused in part by the harvest and preparation of the conduit. The use of Brilliant Blue FCF (FCF) restores injury-induced loss of function in vascular tissues possibly via inhibition of purinergic receptor signaling. This study investigated whether pretreatment of the vein graft with FCF prevents intimal hyperplasia. METHODS Cultured rat aortic smooth muscle cells (A7r5) were used to determine the effect of FCF on platelet-derived growth factor-mediated migration and proliferation, cellular processes that contribute to intimal hyperplasia. The effectiveness of FCF treatment during the time of explantation on preventing intimal hyperplasia was evaluated in a rabbit jugular-carotid interposition model and in an organ culture model using HSV. RESULTS FCF inhibited platelet-derived growth factor-induced migration and proliferation of A7r5 cells. Treatment with FCF at the time of vein graft explantation inhibited the subsequent development of intimal thickening in the rabbit model. Pretreatment with FCF also prevented intimal thickening of HSV in organ culture. CONCLUSIONS Incorporation of FCF as a component of vein graft preparation at the time of explantation represents a potential therapeutic approach to mitigate intimal hyperplasia, reduce vein graft failure, and improve outcome of the autologous transplantation of HSV.

A novel therapy to promote axonal fusion in human digital nerves.

BACKGROUND Peripheral nerve injury can have a devastating impact on our military and veteran population. Current strategies for peripheral nerve repair include techniques such as nerve tubes, nerve grafts, tissue matrices, and nerve growth guides to enhance the number of regenerating axons. Even with such advanced techniques, it takes months to regain function. In animal models, polyethylene glycol (PEG) therapy has shown to improve both physiologic and behavioral outcomes after nerve transection by fusion of a portion of the proximal axons to the distal axon stumps. The objective of this study was to show the efficacy of PEG fusion in humans and to retrospectively compare PEG fusion to standard nerve repair. METHODS Patients with traumatic lacerations involving digital nerves were treated with PEG after standard microsurgical neurorrhaphy. Sensory assessment after injury was performed at 1 week, 2 weeks, 1 month, and 2 months using static two-point discrimination and Semmes-Weinstein monofilament testing. The Medical Research Council Classification (MRCC) for Sensory Recovery Scale was used to evaluate the level of injury. The PEG fusion group was compared to patient-matched controls whose data were retrospectively collected. RESULTS Four PEG fusions were performed on four nerve transections in two patients. Polyethylene glycol therapy improves functional outcomes and speed of nerve recovery in clinical setting assessed by average MRCC score in week 1 (2.8 vs 1.0, p = 0.03). At 4 weeks, MRCC remained superior in the PEG fusion group (3.8 vs 1.3, p = 0.01). At 8 weeks, there was improvement in both groups with the PEG fusion cohort remaining statistically better (4.0 vs 1.7, p = 0.01). CONCLUSION Polyethylene glycol fusion is a novel therapy for peripheral nerve repair with proven effectiveness in animal models. Clinical studies are still in early stages but have had encouraging results. Polyethylene glycol fusion is a potential revolutionary therapy in peripheral nerve repair but needs further investigation. LEVEL OF EVIDENCE Therapeutic study, level IV.

The Clinical Role of Intraoperative Core Temperature in Free Tissue Transfer.

BackgroundLengthy microvascular procedures carry hypothermia risk, yet limited published data evaluate the overall impact of core temperature on patient and flap morbidity. Although hypothermia may contribute to complications, warming measures are challenged by conflicting reports of intraoperative hypothermia improving anastomotic patency. MethodsA retrospective review included all free flaps performed by plastic surgeons at an academic medical center from December 2005 to December 2010. Intraoperative core temperatures were measured by esophageal probe, and median values recorded over 5-minute intervals yielded a case mean (Tavg), maximum (Tmax), and nadir (Tmin). Outcomes included flap failure, pedicle thrombosis, recipient site infection and complications associated with patient, and flap morbidity. Analysis used Student t test, Fisher exact test, Probit, and logistic regression. ResultsOf 156 consecutive free tissue transfers, the median Tavg, Tmax, and Tmin were 36.5°C, 37.1°C, and 35.8°C, respectively. The flap failure rate was 7.7% (12/156) and pedicle thrombosis occurred in 9 (6%) cases. Core temperatures did not associate with overall flap failure or pedicle thrombosis but recipient site infection occurred in 21 (13%) patients who had significantly lower mean core temperatures (Tavg = 36.0°C, P < 0.01). Lower Tavg and Tmax significantly predicted recipient site infection (P < 0.01 and P < 0.05, respectively). Cut-point analysis revealed significant increases in recipient site infection risk at Tavg less than 37.0°C (P = 0.026) and Tmin less than or equal to 34.5°C (P = 0.020). ConclusionsIntraoperative hypothermia posed significant risk of flap infection with no benefit to anastomotic patency in free tissue transfer.

Adjuvant neurotrophic factors in peripheral nerve repair with chondroitin sulfate proteoglycan-reduced acellular nerve allografts.

BACKGROUND Acellular nerve allografts are now standard tools in peripheral nerve repair because of decreased donor site morbidity and operative time savings. Preparation of nerve allografts involves several steps of decellularization and modification of extracellular matrix to remove chondroitin sulfate proteoglycans (CSPGs), which have been shown to inhibit neurite outgrowth through a poorly understood mechanism involving RhoA and extracellular matrix-integrin interactions. Chondroitinase ABC (ChABC) is an enzyme that degrades CSPG molecules and has been shown to promote neurite outgrowth after injury of the central and peripheral nervous systems. Variable results after ChABC treatment make it difficult to predict the effects of this drug in human nerve allografts, especially in the presence of native extracellular signaling molecules. Several studies have shown cross-talk between neurotrophic factor and CSPG signaling pathways, but their interaction remains poorly understood. In this study, we examined the adjuvant effects of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on neurite outgrowth postinjury in CSPG-reduced substrates and acellular nerve allografts. MATERIALS AND METHODS E12 chicken DRG explants were cultured in medium containing ChABC, ChABC + NGF, ChABC + GDNF, or control media. Explants were imaged at 3 d and neurite outgrowths measured. The rat sciatic nerve injury model involved a 1-cm sciatic nerve gap that was microsurgically repaired with ChABC-pretreated acellular nerve allografts. Before implantation, nerve allografts were incubated in NGF, GDNF, or sterile water. Nerve histology was evaluated at 5 d and 8 wk postinjury. RESULTS The addition of GDNF in vitro produced significant increase in sensory neurite length at 3 d compared with ChABC alone (P < 0.01), whereas NGF was not significantly different from control. In vivo adjuvant NGF produced increases in total myelinated axon count (P < 0.005) and motor axon count (P < 0.01), whereas significantly reducing IB4+ nociceptor axon count (P < 0.01). There were no significant differences produced by in vivo adjuvant GDNF. CONCLUSIONS This study provides initial evidence that CSPG-reduced nerve grafts may disinhibit the prosurvival effects of NGF in vivo, promoting motor axon outgrowth and reducing regeneration of specific nociceptive neurons. Our results support further investigation of adjuvant NGF therapy in CSPG-reduced acellular nerve grafts.