Annual Resident Research Day

COMPETITION PAPERS

1. Benedict, L, Paulus, J, Rideout, L, Chwals, W.  Does injury severity predict CT scan utilization at referring institutions prior to transfer to a pediatric trauma center?

Objective:  Computed Tomography (CT) scans performed at referring institutions risk transfer delays and duplicate scanning at destination pediatric trauma centers (PTC) for definitive care. In a cohort of our pediatric trauma patients transferred from outside institutions, we evaluated the relationship between injury severity score (ISS) and CT scans performed.  Methods:  In this 4-year retrospective cohort study, demographic data, injury profiles, ISS and CT scan obtained were abstracted from patient medical records and our pediatric trauma registry.  Crude odds ratios and 95% confidence intervals were calculated with CT scan’s obtained as the primary outcome (Fisher’s exact test, p<0.05). Results: 422 patients were reviewed from 2008-2012.  Severely injured patients (ISS>15) were three times more likely to obtain a CT scan at a referring institution compared to those who were less severely injured (odds ratio, 2.95; 95% confidence interval, 1.19-7.3; p-value, .015).  Furthermore, in the subgroup of children transferred without pre-transfer scans (160/422), CT scans obtained after evaluation at our PTC were reduced to 20% in patients with ISS <15.  Conclusion: Despite the inability to provide definitive care, severely injured children were three times more likely to obtain a CT scan at one of our referring institutions prior to transfer to our Level I PTC. 

2. Bugaev N, Breeze JL, Daoud V, Arabian SS, Rabinovici R. Management and Outcome of Patients with Blunt Splenic Injury and Preexisting Liver Cirrhosis.

Objective:  The response of liver cirrhosis (LC) patients to abdominal trauma, including blunt splenic injury (BSI) is unfavorable. To better understand the response to BSI in LC patients, the present study reviewed a much larger group of such patients, derived from the National Trauma Data Bank (NTDB). Methods: NTDB was queried for 2002-2010, and all adult BSI patients without severe brain trauma were identified. LC and no-LC patients were compared using non-operative management (NOM) failure and mortality as primary outcomes. Predictors of these outcomes in LC patients were identified.  Results:  Of the 77,753 identified BSI patients, 289 (0.37%) had LC. Overall, 90% of patients underwent initial NOM (86% in LC and 90% in no-LC patients, p=0.091) with a global 90% success rate. Compared to non-cirrhotic patients, LC patients had a lower NOM success rate (83 vs. 90%, p=0.004) despite increased utilization of splenic artery angioembolization (13 vs. 8%, p=0.001). LC patients also had more complications/patient, a longer hospital and ICU length of stay, and a higher mortality (23 vs. 6%, p<0.0001), which was independent of the treatment paradigm.  In the LC group, mortality in those who underwent immediate surgery was 35% vs. 46% in failed NOM (p=0.418) and 14% (p=0.019) in successful NOM patients. LC patients who did not require surgery were more likely to survive than those who had surgery alone (AOR-0.30). Preexisting coagulopathy (AOR-3.28) and Grade 4-5 BSI (AOR-11.6) predicted NOM failure in LC patients, whereas male gender (AOR- 4.34), hypotension (AOR-3.15), preexisting coagulopathy (AOR-3.06), and Glasgow Coma Scale <13 (AOR-6.33) predicted mortality. Conclusion: LC patients have a higher rate of complications, mortality and NOM failure than no-LC patients. As LC patients with failed NOM have similar mortality as those undergoing immediate surgery, judgment must be exerted in selecting initial management options.

3. Nabzdyk CS, Icli B, Lujan-Hernandez J, Cahill M, Giatsidis G, Orgill DP, Feinberg MW. miRNA-26a Silencing in a Murine Model of Diabetic Wound Healing.

Objective: Diabetes related wound healing complications pose an enormous clinical challenge. Microvascular dysfunction and decreased angiogenesis contribute to the impaired wound healing. MicroRNA 26a (miR-26a) has been shown to inhibit proangiogenic BMP-SMAD1 signaling in infarcted mouse myocardium. MiR-26a silencing increased angiogenesis and improved ventricular remodeling. This study investigates whether similar effects can be achieved in a diabetic mouse model of cutaneous wound healing. Methods: Skin on the dorsum of DB/DB mice was injected twice with non-specific control (NS) or miR-26a anti-miRs (LNA-anti-miR-26a) in a field block pattern prior (48h and 24h) to excising a 1x1cm2 skin flap. Serial imaging of the wound was performed to assess closure rate until day 9 when wounds were harvested. Q-RT-PCR was used to evaluate effects of miR-26a silencing on BMP-Smad1 signaling. Wound bed granulation thickness and angiogenesis were assessed histologically. Results: Anti-miR26a silenced miR-26a in the wound throughout Day 9 (1.6 x10-3, p< 0.05). A trend towards increased SMAD1 (8.3 fold, p>0.05) and significantly increased expression of inhibitor of DNA binding protein 1 (ID1) (2.7 fold, p<0.05) were noted. Compared to NS, anti-miR26a also enhanced wound closure (99% vs. 54%, relative wound size, p<0.05), granulation tissue thickness (2.3 fold, p<0.05) and angiogenesis (48.2 vs. 108.3 (CD31 count/HPF), p<0.05). Conclusions: This data showed that cutaneous miR-26a silencing in DB/DB mice improved wound healing with increased angiogenesis and granulation tissue formation. Increased SMAD1-ID1 signaling may underlie these effects. Additional experiments will further delineate molecular and cellular mechanisms involved and show whether this approach may be used for a clinical application.

4. Saur NM, England MR, Menzie W, Melanson A, Trieu M, Berlin J, Hurley J, Krystyniak K, Kongable GL, Nasraway SA.  Accuracy of a novel noninvasive transdermal continuous glucose monitor in critically ill patients. WINNER!!!

Objective:  Stress hyperglycemia and hypoglycemia are associated with increased morbidity and mortality in the critically ill. Intermittent and random blood glucose (BG) measurement can miss episodes of hyper- and hypoglycemia.  The purpose of this study was to determine the accuracy of the Symphony^® continuous glucose monitor (CGM) in critically ill cardiac surgery patients.    Methods:  Fifteen adult cardiac-surgery patients were evaluated immediately postoperatively in the intensive care unit between February 15 and April 1, 2012.  Prelude^® SkinPrep prepared the skin and a sensor was applied to two test sites on each subject to monitor interstitial fluid glucose.  Reference BG was sampled at 30-60 minute intervals. The skin at the test sites was inspected for adverse effects. Accuracy of the CGM data relative to reference BG values was determined using Continuous Glucose-Error Grid Analysis (CG-EGA) and mean absolute relative difference (MARD). Results:  Using 570 Symphony CGM glucose readings paired with reference BG measurements, CG-EGA showed that 99.6% of the readings were clinically accurate.  BG measurements ranged from 73 to 251 mg/dL. The MARD was 12.3%. No adverse device effects were reported. Conclusions:  The Symphony CGM system is able to safely, continuously and non-invasively monitor glucose in the transdermal interstitial fluid of cardiac surgery intensive care unit patients with accuracy similar to that reported with other CGM systems.

5. Traa MX, Barboza, L, Doron, S, Snydman, DR, Noubary, F, Nasraway, SA. Horizontal Infection Control Strategy Decreases Methicillin-resistant Staphylococcus aureus Infection and Eliminates Bacteremia in a Surgical ICU Without Active Surveillance.

Objective: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a significant contributor to morbidity and mortality in hospitalized patients worldwide.  Numerous healthcare bodies in Europe and the United States have championed active surveillance per the ‘search and destroy’ model.  However this strategy is associated with significant economic, logistical and patient costs without any impact on other hospital-acquired pathogens.  We evaluated whether horizontal infection control strategies could decrease the incidence of MRSA infection in the ICU, without the need for active surveillance. Methods: Retrospective, observational study of 6,697 patients in the surgical intensive care unit (surgical ICU) of a tertiary care medical center in Boston, Massachusetts from 2005-2012.  Evidence-based infection prevention strategies were implemented in an iterative fashion, including 1) hand hygiene program with refresher education campaign, 2) chlorhexidine oral hygiene program, 3) chlorhexidine bathing, 4) catheter-associated bloodstream infection program, and 5) daily goals sheets. Results: The incidence of MRSA infection fell from 2.66 to 0.69 per 1000 patient days from 2005 to 2012, an average decrease of 21% per year. The biggest decline in rate of infection was detected in 2008, which may suggest that the catheter-associated bloodstream infection prevention program was particularly effective.  Among 4,478 surgical ICU admissions over the last 5 years, not a single case of MRSA bacteremia was observed.        Conclusion: Aggressive multifaceted horizontal infection control is an effective strategy for reducing the incidence of MRSA infection and eliminating MRSA bacteremia in the ICU without the need for active surveillance and decontamination.

SHORT PRESENTATIONS

1. Dermody, M, O’Donnell TF, Balk, E.  Complications of endovenous ablation in randomized controlled trials.

Objective: Endovenous ablation (EVA) of the great saphenous vein (GSV), with radiofrequency (RFA) or laser ablation (EVLA), has largely replaced the standard ligation and stripping (L&S).  Several randomized controlled trials (RCT) have reported data on efficacy of the ablation with little focus on complications.  We analyzed the current literature for short-term complications of EVA as compared to L&S. Methods: We searched MEDLINE, the Cochrane Central Trials Registry, and individual journals from January 2008 through January 8, 2013 for RCTs comparing RFA and/or EVLA and/or L&S to treat GSV incompetence.  We excluded studies using foam sclerotherapy, re-do GSV surgery, or the addition of a high GSV ligation to an EVA procedure.  We meta-analysized short-term (<1 year) complications using the Peto odds ratio to elucidate differences between RFA (using the VNUS® ClosureFAST™ catheter), EVLA, and L&S. Results: Seventeen RCTs met inclusion criteria.  There were 317 patients who underwent RFA with ClosureFAST™, 1057 patients who had EVLA, and 975 who had L&S.  70% were female with a mean age of 47.5 years.  The majority had CEAP clinical class 2 or 3.  There was an overall complication rate of 39.6% in the 2624 limbs analyzed over all procedures.  There was no evidence of a difference in the rates of venous thromboembolism.  There was a significantly higher rate of wound infection for L&S (2.3%; 95% CI 1.3-3.1%) vs EVLA (0.5%; 95% CI 0.3-1.3%; P=.006), but not between L&S and RFA (1.5%; 95% CI 0.4-3.0%; P=.094).  The paresthesia rate was significantly lower with EVLA (3.8%; 95% CI 2.4-4.5%) as compared to RFA (5.2%; 95% CI 3.1-7.9%; P<.001) and L&S (7.4%; 95% CI 5.3-8.3%; P<.001).  The rate of thrombophlebitis was significantly lower for L&S (3.0%; 95% CI 2.9-4.0%) as compared to RFA (5.5%; 95% CI 3.0-7.8%; P=.003) and EVLA (5.6%; 95% CI 4.2-7.0%; P=.003).  There was no difference in the rate of thermal skin burns between RFA and EVLA. Conclusions: Endovenous ablation and ligation and stripping of the GSV are not without complications, although usually minor.  L&S has a higher wound infection rate and lower thrombophlebitis rate as compared to EVA.  EVLA has a significantly lower rate of paresthesia as compared to RFA and L&S.  Thermal skin burns occur with equal frequency in RFA and EVLA. 

2. Morrison SA, Hodin R, Sadow P, Lubitz C, Stephen A. Diffuse Sclerosing Variant of Papillary Thyroid Cancer: A Risk Factor for Recurrent Laryngeal Nerve Involvement.

Objective: Diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare variant of papillary thyroid carcinoma (PTC), accounting for 0.7%-5.3% of PTC cases. This variant historically exhibits more aggressive behavior than classical PTC.  However, prior studies have been few in number and have not investigated the role and potential consequences of recurrent laryngeal nerve (RLN) involvement. In this series, we present the incidence and implications of nerve involvement in this PTC variant. Methods: Thirty-four patients were retrospectively reviewed over a 13 year period at a single institution. Records from patients undergoing thyroidectomy were queried from a pathologic database. Patients were selected for inclusion if three or greater criteria were met for diffuse sclerosing variant, as defined by the WHO. Clinical and histopathological characteristics of study patients were reviewed and compared to values reported in the literature for patients with classical PTC. Operative reports and laryngoscopies were reviewed for evidence of nerve involvement and post-operative paralysis. Results: Compared to classical PTC, our study patients were more likely to be younger (average age 40 vs. 46), have larger tumors (3.9cm vs. 2.2cm), with higher rates of cervical lymph node involvement (90.6% vs. 43.0%). Our case series revealed a significantly greater incidence of multifocality (87.5% vs. 17.2%) and extra-thyroidal extension (75.8% vs 59.6%). Additionally, DSPC study patients were more likely to have persistent or recurrent disease (26.9% vs 17.2%) as well as distant metastasis (11.5% vs. 4.3%). Our cohort demonstrated a 30% incidence of RLN involvement as reported by the operating surgeon, resulting in vocal cord palsy in 7/34 patients (20.6%). Three of these seven patients underwent intentional nerve sacrifice. The remaining 4 patients had transient vocal cord palsies that resolved.    Conclusions: In this series, DSV-PTC was associated with greater infiltration and aggressive behavior compared to patients with classical PTC. In particular, RLN involvement was noted in 30% of patients, and the incidence of post-operative RLN palsy was 20.6%. These findings have important implications with regard to the pre-operative work-up, intra-operative decision making, and post-operative management of patients with DSV-PTC.

3. Traa MX, Saur NM, Almussallam B, Orkin BA, Popowich DA.  The Effect of Chronic Narcotic Use on CT Scan Yield in Crohn’s Disease.

Objective: Computed tomography (CT) is increasingly relied upon above clinical examination as the modality of choice in determining management of patients with Crohn’s disease presenting with new complaints. A CT of the abdomen and pelvis exposes a patient to 10mGy/mSv radiation, which has been correlated with a greater incidence of cancer. We aimed to identify factors that predict low-yield CT scans and to compare our data to previous work and our previously analyzed small-scale pilot study. Methods: A retrospective chart review was conducted for 86 patients with Crohn’s disease at Tufts Medical Center between May 2009 and October 2012. Data gathered included number of emergency department (ED) visits; hospital admissions; operations; diagnostic studies performed (CT, magnetic resonance imaging, small bowel follow through, endoscopy); chronic narcotic use; attendance at surgery, gastroenterology, or pain clinic; and number of missed visits. Chi-square comparisons were made with p-values <0.05 considered significant. Results: Compared to non-narcotic users, narcotic users were more likely to have ED visits (93% vs 54%, p= 0.0067), hospital admissions (93% vs 75%, p=0.178), and CT scans (100% vs 57% p=0.0015). Patients who are on chronic narcotics represent 54 percent of the total CTs done for Crohn’s patients despite only representing 19 percent of our Crohn’s population. Additionally, chronic narcotic users’ mean ED visit frequency was 1.5-times higher than those patients who do not use chronic narcotics and is associated with a two-fold higher likelihood of being admitted to the hospital. Additionally, the ratios of CT scans to operation and CT scans to hospital admission were higher in the chronic narcotic group, whereas the ratio of ED visits to operation was identical between groups (Table 1). Conclusion: We have identified chronic use of narcotics as a significant predictor of low-yield CT scans. Crohn’s patients who are on chronic pain medications should be managed without a CT scan unless their pain is significantly changed from their baseline. Reducing the scan burden in this population will decrease both health care financial cost and ionizing radiation risk to these patients.

Competition Oral Presentations

1. Benedict, LA, Paulus JK, Rideout L, Walter J. Chwals WJ. Are CT scans obtained at referring institutions justified prior to transfer to a pediatric trauma center?

Objective: Computed Tomography (CT) imaging has been used with increasing frequency in the evaluation of pediatric trauma patients. Referring institutions often use CT scans for the evaluation of injuries in these patients, ostensibly to determine the necessity for transfer to a pediatric trauma center. We evaluated a cohort of pediatric trauma patients who received CT scans at referring institutions to determine whether state guidelines for stabilization and immediate transfer to a pediatric trauma center without pre-transfer CT imaging were met. Methods: This was a 3-year retrospective cohort study completed at our level 1 pediatric trauma center. Pediatric trauma patients who had CT imaging at referring institutions were classified according to whether state criteria were met for immediate transfer. Demographic data and injury profile characteristics were abstracted from patient medical records and our pediatric trauma registry. Results: A total of 262 patients with 413 CT scans were reviewed from 2008-2011 and 244 (59%) of those CT scans were negative for any injury. Of the 138 patients 10 years of age or younger, 63 (45%) had negative CT scans. 172 patients scanned (66%, 95% CI: 60%, 71%) met criteria for immediate transfer to a pediatric trauma center with 143 of those patients (83%) having injuries that required a higher level of care. GCS score <14 (45%) was the most common requirement for transfer and CT scan of the head was the most frequent scan obtained (53%). Conclusion: The majority of pediatric trauma patients were subjected to CT scans at referring institutions despite meeting statewide trauma guidelines for stabilization and immediate transfer to a pediatric trauma center without any CT imaging. Furthermore, the majority of pre-transfer CT scans were negative and provided no clinical benefit in determining the need for transfer.

2. Benedict LA, Wang D, Cameron D, Pepin D, Hendren K, Sosulski A, Li H, Gao G, RH Brown, and Donahoe PK. Spinal cord expression of virally delivered Mullerian Inhibiting Substance extends life and promotes survival of motor neurons in transgenic SOD1^mutant mice. WINNER!!!

Objective: Motor neuron diseases are a group of neurological disorders caused by slowly progressive death of motor neurons, which control essential voluntary muscle activity. Mullerian Inhibiting Substance (MIS) is a member of the TGF-β superfamily, which includes other motor-neuron survival factors. Since MIS and its receptors are expressed in motor neurons, we hypothesized that heightened spinal cord expression of MIS would prolong survival in SOD1 mutated mice. Methods: Adeno-Associated virus serotype 9 was used to deliver Mullerian Inhibiting Substance (AAV9-MIS) as a single intravenous injection at P28 (n=4 with 4 controls), P7 (n=7), or P1 (n=9) into C57/BL6 mice carrying the G93A superoxide dismutase (SOD1) mutation that occurs in 20-25% of patients with familial ALS. Genome copy number was analyzed from liver and brain specimens at disease end point to quantify the presence of vector. Phosphate buffered saline (PBS) was compared to Mullerian Inhibiting Substance for effect on the size and number of motor neurons by both immunohistochemistry and immunofluorescence of spinal cord sections using the motor neuron marker choline acetyltransferase. Results: SOD1 mutated mice injected with the AAV9-MIS vector demonstrated a 15 day survival benefit when compared to mice injected with PBS (P28, *p=0.026; P7, *p=0.038; P1, *p=0.013). In addition, endstage AAV9-MIS injected mice showed more robust ChAT staining in the ventral horns of the spinal cord by immunofluorescence (FIGURE 1A-RED) when compared to control (FIGURE 1B-RED). Furthermore, AAV9-MIS injected mice demonstrated more axonal staining in the ventral horn of the spinal cord by immunohistochemistry (FIGURE 1C-PURPLE) when compared to control (FIGURE 1D-PURPLE). Conclusion: The in vivo responses produced by virally delivered MIS indicates its use as an effective method for prolonging survival of patients with neurological diseases such as ALS and that neurotropic viral gene therapy may be an efficient mode of delivery of MIS.

3. Benoit E, O’Donnell TF, Kitsios GD, Iafrati MD. Improved amputation-free survival in unreconstructable critical limb ischemia and its implications for clinical trial design and quality measurement.

Objective: Amputation-free survival (AFS), a composite endpoint of mortality and amputation, is the preferred outcome measure in critical limb ischemia (CLI). Given the improvements in systemic management of atherosclerosis and interventional management of limb ischemia over the past 2 decades, we examined whether these outcomes have changed in patients with CLI without revascularization options (no option-critical limb ischemia [NO-CLI]). Methods: We reviewed the literature for published 1-year AFS, mortality, and amputation rates from control groups in NO-CLI trials. Summary proportions of events were estimated by conducting a random effects meta-analysis of proportions. To determine whether there had been any change in event rates over time, we performed a random effects meta-regression and a mixed effects logistic regression, both regressed against the variable "final year of recruitment." Results: Eleven trials consisting of 886 patients satisfied search criteria, 7 of which presented AFS data. Summary proportion of events (95% confidence interval) were 0.551 (0.399 to 0.693) for AFS; 0.198 (0.116 to 0.317) for death; and 0.341 (0.209 to 0.487) for amputation. Regression analyses demonstrated that AFS has risen over time as mortality rates have fallen, and these improvements are statistically significant. The decrease in amputation rates failed to reach statistical significance. The lack of published data precluded a quantitative evaluation of any change in the clinical severity or comorbidities in the NO-CLI population. Conclusions: AFS and mortality rates in NO-CLI have improved over the past 2 decades. Due to declining event rates, clinical trials may underestimate treatment effects and thus fail to reach statistical significance unless sample sizes are increased or unless a subgroup with a higher event rate can be identified. Alternatively, comparing outcomes to historical values for quality measurement may overestimate treatment effects. Benchmark values of AFS and morality require periodic review and updating.

4. Morrison S, Graham R, Hill S, Price L, Holcroft C, Rogers G. Efficacy and Safety of Continuous Low Irradiance Photodynamic Therapy (CLIPT) in the Treatment of Cutaneous Recurrence of Breast and Dermal Malignancies.

Objective: Photodynamic therapy (PDT) is an important treatment for patients with both pre-malignant and malignant conditions. CLIPT is a novel modification of PDT that enhances tumor specific cytotoxicity while minimizing necrosis to adjacent healthy tissue. This phase I clinical trial was designed to determine the maximum tolerated dose (MTD) and tumor response using CLIPT for cutaneous recurrence of both breast and dermal malignancies. Methods: The study design planned for sequential cohorts of 6 patients to be treated at increasing laser intensity, starting at 100 j/cm². Dose limiting toxicity (DLT) was defined as full thickness necrosis. The MTD was defined as the highest dose level at which < 33% of patients experienced the DLT. Patients were injected with Photofrin and then underwent 24 hours of continuous photodynamic therapy. Also assessed were clinical and pathologic response rates and quality of life measures. Results: Eleven patients were enrolled: 9 with recurrent breast cancer and 2 with recurrent dermal cancers. Two patients were treated at 100 j/cm² and suffered full thickness skin necrosis. The next cohort of patients was therefore dose reduced and treated at 50 j/cm². One of the subsequent 9 patients suffered full thickness necrosis, thus establishing the MTD at 50 j/cm². Eight of 11 patients (73%) demonstrated either a complete or partial clinical response. Interestingly, two patients had significant regression of tumor nodules distant from the treatment field. Quality of life measures were generally improved following treatment - particularly bleeding and pain from the tumor nodules. Of the 8 patients whose TUNEL assay results were available, 8 (100%) demonstrated a pathologic response to treatment as evidenced by either tumor apoptosis or regression. Conclusions: The MTD of CLIPT was established at 50 j/cm2. CLIPT is a highly effective therapeutic modality in the treatment of dermal recurrence of both breast and cutaneous malignancies.

5. Nabzdyk CS, Glaser JD, Chun M, Pathan S, Phaneuf M, You JO, Pradhan L, LoGerfo FW. Composite Electrospun Polyethylene Terephtalate Materials for Arterial Bypass Grafting.

Objective: Intimal hyperplasia (IH) is the leading cause of prosthetic arterial graft failure. Electrospun polyethylene terephthalate (ePET) is an interesting alternative to commercially available grafts. The combination of non-degradable PET with degradable polymers such as polyglycolic acid (PGA) may be developed into biologically active prosthetic arterial bypass grafts. Methods: Graft materials synthesized were: unmodified ePET, ePET/ePGA as a co-polymer (PET/PGA mixture resulting in one continuous fiber) and co-electrospun ePET/ePGA fabric (individual PET and PGA fibers interspersed). Materials were incubated in saline at 37°C for 7, 14 and 21 days. For imaging, scanning electron microscopy (SEM) was used. Human aortic smooth muscle cells (HAoSMCs) were seeded onto the materials. Attachment and viability were analyzed 3 and 48 hours later by alamar blue assay. Commercial PTFE served as comparison. Results: ePET fibers had a diameter of 1-2µm while ePGA fibers measured 0.2-0.5µm. At 14d and 21d ePET/ePGA co-polymer fabrics showed strand breaks on SEM while co-electrospun ePET/ePGA showed intact PET fibers with little residual ePGA. Compared to PTFE, electrospun materials had higher attachment rates and viability indices of HAoSMC, suggesting cellular proliferation. No differences in HAoSMC attachment and viability were observed between electrospun materials. Conclusion: This preliminary data suggests that eletrospun composite ePET/ePGA materials do not impair HAoSMC attachment compared to ePET. Overall, electrospun materials provide higher HAoSMC attachment rates than commercial PTFE. Further, co-electrospun ePET/ePGA fabrics were intact after PGA degradation, while ePET/ePGA co-polymer showed strand breaks. Thus co-electrospinning of PET and degradable PGA might lead to novel prosthetic arterial grafts.

Short Oral Presentations

1. Benoit E, O’Donnell TF, Patel AN. Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review.

Objective: Researchers have accumulated a decade of experience with autologous cell therapy in the treatment of critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of cell therapy in CLI. We searched the literature for clinical trials of autologous cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Methods: Safety analysis included evaluation of death, cancer, unregulated angiogenesis, and procedural adverse events such as bleeding. Efficacy analysis included the clinical endpoints amputation and death as well as functional and surrogate endpoints. Results: We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received cell therapy. The overall adverse event rate was low (4.2%). Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in cancer incidence when analyzed against population rates. With regard to efficacy, cell therapy patients had a significantly lower amputation rate than control patients (OR 0.36, p = 0.0004). Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Conclusions: Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of amputation and death. Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and cancer and treatment with cell therapy decreases the risk of amputation. Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.

2. Nabzdyk CS, Chun M, Oliver-Allen H, Phaneuf M, Pathan S, You JO, Pradhan L, LoGerfo FW. Polyethyleneimine (PEI) siRNA Complexes Released From Coated Electrospun Polyethylene Terephthalate (PET) Bypass Graft Materials Facilitate Gene Silencing in Infiltrating Primary Human Aortic Smooth Muscle Cells.

Objective: Anastomotic Intimal hyperplasia (AIH) remains the leading cause of prosthetic arterial graft failure. Use of electrospun PET (ePET) can be an alternative to conventional PET grafts. RNAi is a promising tool to silence genes contributing to AIH, including, Thrombospondin-2 (TSP-2) previously shown by us to be upregulated in AIH. Delivery of silencing RNA (siRNA) from ePET graft to the anastomotic sites could potentially mitigate AIH. Methods: ePET was dip-coated with control siRNA alone or complexed with either, cationic polymer polyethyleneimine (PEI) or the lipophilic transfection reagent Lipofectamine RNAiMax for 45 minutes. UV-Spectrophotometry was used to quantify siRNA coating on ePET. Control and TSP-2 siRNA-PEI complexes coated ePET samples (5x5mm²) were placed onto a monolayer of human aortic smooth muscle cells (HAoSMCs) for 24 hours. Confocal microscopy and Q-RT-PCR were performed to evaluate cellular infiltration into ePET and gene silencing of TSP-2. Results: Significant amount of siRNA from the coating solution was adsorbed to ePET if complexed with PEI compared to RNAiMax or no transfection reagent (62%±3% vs. 1%±0.075% or 1.0%±0.01%), HAoSMCs migrated into and proliferated on ePET coated with siRNA-PEI complexes. Compared to control siRNA, TSP-2 siRNA uptake in HAoSMC resulted in significant gene silencing of TSP-2 from ePET coated with siRNA-PEI. Conclusions: Coating of ePET with siRNA-PEI complexes is feasible, does not impair HAoSMCs in-growth and facilitates TSP-2 gene silencing in HAoSMC in vitro. This clinically feasible approach for delivery of target gene siRNAs may help prevent AIH and subsequent graft failure.

3. Traa MX, Barboza L, Doron s, Snydman D, Nasraway SA. Defying Methicillin-resistant Staphylococcus aureus and Eliminating Bacteremia in a Surgical ICU Without Active Surveillance.

Objective: Methicillin resistant staphylococcus aureus (MRSA) is a significant contributor to morbidity and mortality in intensive care units and hospitals around the world. Active surveillance with the ‘search and destroy’ model has been championed by a number of healthcare bodies in Europe and the United States. However this strategy has been associated with significant economic, logistical, and patient costs. Methods: We conducted a retrospective, observational study with quasi-experimental design of MRSA infections in 8,460 patients in the surgical intensive care unit (SICU) of a major tertiary care center in Boston, Massachusetts over a ten-year period from 2002-2012. Incidence of MRSA positive infections was measured for the final five years from 2007-2012, after cessation of an active surveillance culture program. Numerous evidence-based infection prevention strategies were implemented in an iterative fashion, including 1) hand hygiene program, 2) oral chlorhexidine rinses, 3) chlorhexidine bathing, 4) catheter-associated bloodstream infection program (including chlorhexidine skin preparation, chlorhexidine-coated central venous catheters and chlorhexidine-impregnated dressings), 5) daily goal sheets, and 6) refresher education campaigns to combat hand-hygiene protocol fatigue. Weighted linear regression analysis was used to calculate statistical significance of the decline of MRSA incidence. Results: Over the final five-year study period, the MRSA incidence fell by 47% per year from 2.9 per 1000 patient years in 2007 to 0.69 per 1000 patient years in 2012 (p=0.0067). During these years the MRSA bacteremia rate was zero of 4,478 patients. To the author’s knowledge this is the lowest reported MRSA bacteremia rate in an ICU. Interestingly, the rate of MRSA resistance also declined, from 70% to just 18% during the ten-year study period. Conclusion: An aggressive infection control strategy achieves significant reductions in the incidence of MRSA infection and eliminates MRSA bacteremia in the ICU without the costs and negative effects of active surveillance and isolation. Hospitals should focus on thorough infection prevention rather than the ‘search and destroy’ approach to efficiently and effectively defy the scourge of MRSA.

1. Chhabra, N, Crosslin, T, D’Achille, J, Holewinski, S, Hudson-Jinks, TM, Nasraway, SA. Report of Mortality and other Outcomes of Patients in a Surgical Intensive Care Unit: Strengths and Limitations of the Standardized Mortality Ratio.

Objective: There has been a radical acceleration in the volume and implementation of evidence-based processes of care in the ICU. Little is known about the effects of these changes in the aggregate on outcomes for the critically ill. Methods: Numerous evidence-based protocols were implemented to improve patient care, physician communication and to decrease hospital-acquired infections. We performed a cohort study of prospectively evaluated patients from a ten bed surgical intensive care unit at an academic medical center in Boston. The primary cohort was all patients admitted to the surgical intensive care unit from March 2010 through February 2012 and related outcomes. The change in standardized mortality ratio was longitudinally determined from the latest 15-year study period (1997-2011) which comprised 10,172 patients. Results: There were 1,799 intensive care unit admissions in the primary cohort. Hospital mortality, observed and predicted by Acute Physiology and Chronic Health Evaluation IV, was measured. Crude hospital mortality was 8.4%. The standardized mortality ratio (observed/predicted mortality) was 0.58 (95% CI: 0.49-0.65). The standardized mortality ratio decreased by 20% from 0.73 to 0.54 over the 15-year study period, an absolute 1% per year decrease (p = 0.039; CI -.02 to -.002). Approximately 562 additional lives were saved from among the 10,172 patients admitted during this longitudinal period. Conclusions: Mortality was less than predicted and steadily declined during the previous 15 years with the introduction of evidence-based protocols to improve the process of care.

2. Driscoll, D, Herman, L, D’Achille, J. Suction-assisted Lipectomy with Dermal Mastopexy: A Superior Procedure in Repeat Reduction Mammaplasty with Questionable Nipple-areola Complex Vascularity.

3. Saur NM, Kongable GL, Holewinski S, O’Brien K, Nasraway SA. Software-Guided Insulin Dosing: Tight Glycemic Control and Decreased Glycemic Derangements in Critically Ill Patients.

Objective: Glycemic control has become an increasingly important element of care in critically ill patients secondary to the discovery that severe stress hyperglycemia is strongly associated with increased mortality. The purpose of this study is to determine whether glycemic derangements are more effectively controlled using software-guided insulin dosing when compared to paper protocols. Methods: We prospectively evaluated consecutive critically ill patients treated in a tertiary- hospital surgical intensive care unit (ICU) from January 1 through June 30, 2008 and January 1 through September 30, 2009. Paper-protocol insulin dosing was evaluated as a baseline during the first time period followed by software-based insulin dosing in the second. We compared glycemic metrics related to hyperglycemia, hypoglycemia and glycemic variability during the two periods. Results: One-hundred and ten patients were treated by paper protocol while eighty-seven were treated with the software protocol during the before and after periods. The mean ICU admission blood glucose (BG) was higher in patients started on software-guided intensive insulin than for patients receiving paper-based intensive insulin (181 vs. 156 mg/dL, p 0.003, mean of the per-patient mean). Patients treated with software-guided intensive insulin therapy had lower mean BG (117 vs. 135 mg/dL, p 0.0008), sustained greater time within the desired BG target range (95-135mg/dL; 68% vs. 52%, p 0.0001), had less frequent hypoglycemia (% of time BG < 70 mg/dL; 0.51% vs. 1.44%, p 0.04) and showed decreased glycemic variability (GV; BG per-patient standard deviation (SD) from the mean, ± 29 vs. ± 42 mg/dL, p 0.01). Conclusion: Surgical ICU patients whose intensive insulin infusions were managed using the software program achieved tighter glycemic control and fewer glycemic derangements than those managed with the paper-based insulin-dosing regimen.

4. Almutairi, H, Ma, H, Rosen, NA, Iafrati, MD. Prolonged Radiation Exposure in IVC Filter Removal.

Objectives: As the rate of inferior vena cava (IVC) filter retrieval increases, so does radiation exposure. We sought to quantify the range of procedure times and radiation doses and to identify factors that predict procedure difficulty. Methods: A single center, retrospective review, of attempted removal of IVC filters from 2005 through 2012 was conducted. Data analysis included: fluoroscopy time (FT), procedure success, radiation dose, operator experience, time since filter placement, filter tilt, and body mass index (BMI). Results: Forty-nine of 52 attempted IVC filter removals were successful. Median FT was 6.9 minutes (range, 1.8- 81.9 minutes). Most filters (79%, n = 41) were removed in less than 15 minutes (uncomplicated). These uncomplicated cases (100% success) had median FT= 5.2 minutes (range, 1.8-13.4 minutes) and estimated skin exposure of 111 mGy. More prolonged cases (21%, n = 11) had FT> 15 minutes, median of 42 minutes (range, 18.5- 81.9 minutes), radiation dose of 2516 mGy, with three failures (27%, 3/11). The “prolonged cases” had a longer interval since insertion (273 days vs 140 days, P = NS) and a greater likelihood of filter tilt (64% vs 10%, P < .0006). Patients with tilted filters received 38.1 minutes FT versus properly aligned of 5.4 minutes (P < .000003). At the time of insertion, none of the “prolonged cases” were tilted. Filter type and BMI did not  affect FT. Operators included three interventional radiologist and three vascular surgeons. While specialty training did not correlate with FT, it is notable that the most junior member of the team accounted for 17% of total cases and 36% of prolonged cases, which were all successful. Conclusion: Most retrievable IVC filters are removed quickly with reasonable radiation exposure. Over time, filters can tilt, resulting is challenges to retrieval, increasing FT, radiation exposure, and likelihood of failure. Filter removal should be scheduled as soon as medically appropriate. When rapid progress is not made, early use of adjuvant techniques may prevent exposure beyond the FDA suggested 1000 mGy limit.

5. Spector, D, Z Perry, Shikora, S. Bariatric Surgery Improves Glucose Control in Obese Patients with Type 1 Diabetes.

Objectives: The prevalence of diabetes is growing worldwide for both Type 1 and Type 2 Diabetes Mellitus (T1DM, T2DM). The association between obesity and T2DM has been well demonstrated, with gastric bypass achieving cure rates above 80%. T1DM patients are usually leaner, but similar to the general rise in obesity, reports are revealing these patients to be more than 35% overweight at onset of disease. Furthermore, intensive insulin treatment causes even more weight gain. It is unclear what role bariatric surgery has with obese T1DM patients; only two case reports have been published. Methods: Retrospective analysis of prospectively collected bariatric surgery patients with T1DM; 5 patients underwent gastric bypass, and 2 gastric banding. Results: The mean postoperative follow-up was 45.4 months. Only one patient suffered a complication (DVT). The preoperative and postoperative results for the mean BMI was 40.05 vs. 31.16 (p=0.018); the mean glucose level was 239 vs. 150 mg/dl (p=0.028); the mean HbA₁c was 8.51 vs. 7.34 (p=0.046); and the mean daily insulin dosage was 54.7 vs. 34.6 units (p=0.028). The effects were more robust for the gastric bypass patients. Conclusions: Bariatric surgery is effective and safe for obese T1DM patients. The results demonstrate that patients after bariatric surgery have better control over glucose levels, require less daily insulin doses, and have lower HbA₁c. These changes are likely the result of a combination of factors including lowered caloric intake, lowered BMI (insulin resistance), and elevated Incretin effect. Possibly, T1DM should be considered a comorbidity strengthening the indication for bariatric surgery.

6. Dermody, M, Alessi-Chinetti, J, Iafrati, M, James M. Estes. The Utility of Screening for Deep Venous Thrombosis in Asymptomatic, Non-Ambulatory Neurosurgical Patients.

Objectives: Decisions regarding deep venous thrombosis (DVT) prophylaxis are complicated in neurosurgical patients because of the potential for catastrophic bleedingcomplications. Screening with venous duplex ultrasound (VDUS) may improve outcomes, but can strain hospital resources. Since there is little data to guide VDUS surveillance,we investigated the utility of a comprehensive VDUS screening program in neurosurgical patients. Methods: Medical records of patients admitted to the neurosurgical service at a university-affiliated hospital from October 2007 through January 2010 who underwent weekly VDUS of the lower extremities until ambulatory or discharged were retrospectively reviewed. Demographics, comorbidities, interventions, and use of DVT prophylaxis were recorded. All patients in this study were asymptomatic for clinical evidence of DVT. When DVT was identified, VDUS reported its location and progression. Results: One hundred seventy-four consecutive patients were screened according to the established protocol. They had 312 VDUS studies, 68 (21.8%) of which were positive in 40 (23%) unique patients; 10 were bilateral and two catheter-related. There were no documented pulmonary emboli in this series. Seventeen patients (37.7%) had isolated calf DVT, four of which were bilateral (totaling 21 thrombi), and 9 (20%) had coexistent thrombi in calf and proximal veins. Of the 21 isolated calf DVTs, 15 had follow-up studies and two progressed to the popliteal or ileofemoral vein on follow-up (13.3%). Mechanical prophylaxis was uniformly utilized, but chemical prophylaxis varied based on surgeons' assessment of bleeding risk. DVT developed in 19.3% (28/145) of patients receiving prophylactic medication (unfractionated heparin or low-molecular weight heparin) and 41.4% (12/29) receiving no chemoprophylaxis (P < .001). The only patient characteristic that correlated with DVT risk was a body mass index <30 (9.1% vs 29.4%, P = .01). Conclusions: Despite the uniform application of mechanical DVT prophylaxis and the use of chemoprophylaxis in a majority of patients, we found a 23% incidence of DVT in these hospitalized, nonambulatory, neurosurgical patients. No patients with isolated calf DVT had an embolic complication but 13.3% progressed proximally in short-term follow-up. While chemical prophylaxis significantly reduced DVT risk, no factor was sufficiently predictive to exclude patients from screening. These data substantiate the importance of full leg VDUS screening and maximizing DVT prophylaxis in this high risk population.

7. Haqqani, O, Agarwal, P, Halin, N, Iafrati, M. Defining the Radiation "Scatter Cloud" in the Interventional Suite.

Objective: We hypothesized that fluoroscopic imaging creates radiation fields that are unevenly scattered throughout the endovascular suite. We sought to quantify the radiation dose spectrum at various locations during imaging procedures and to represent this in a clinically useful manner. Methods: Digital subtraction imaging (Innova 4100; GE Healthcare, Waukesha, Wisc) of the abdomen and pelvis was performed on a cadaver in anteroposterior, left lateral, and right anterior oblique 45° projections. Radiation exposure was monitored in real time with DoseAware dosimeters (Phillips, Houston, Tex) in eight radial projections at distances of 2, 4, and 6 ft from the center of the imaged field, each at 5-ft heights from the floor. Three to five consecutive data points were collected for each location. Results: At most positions around the angiographic table, radiation exposure decreased as the distance from the source emitter increased; however, the intensity of the exposure varied dramatically around the axis of imaging. With anteroposterior imaging, the radiation fields have symmetric dumbbell shapes, with maximal exposure perpendicular to the table at the level of the gantry. Peak levels at 4 and 6 ft from the source emitter were 2.4 times and 3.4 times higher, respectively, than predicted based on the inverse square law. Maximal radiation exposure was measured in the typical operator position 2 ft away and perpendicular to the table (4.99 mSv/h). When the gantry was rotated 45° and 90°, the radiation fields shifted, becoming more asymmetric, with increasing radiation doses to 10.9 and 69 mSv/h, respectively, on the side of the emitter. Minimal exposure is experienced along the axis of the table, decreasing with distance from the source (<0.77 mSv/h). Conclusions: Quantifiable and reproducible radiation scatter is created during interventional procedures. Radiation doses vary widely around the perimeter of the angiography table and change according to imaging angles. These data are easily visualized using contour plots and scatter three-dimensional mesh plots. Rather than the concentric circles predicted by the inverse square law, these data more closely resemble a “scatter cloud.” Knowledge of the actual exposure levels within the endovascular environment may help in mitigating these risks to health care providers.