Risk Factors for Postoperative Infections After Single-Level Lumbar Fusion Surgery.

STUDY DESIGN: Retrospective multivariate analysis of a prospectively collected, multicenter database. OBJECTIVE: To identify patient characteristics and perioperative risk factors associated with postoperative infectious complications after single-level lumbar fusion (SLLF) surgery. SUMMARY OF BACKGROUND DATA: Postoperative infection is a known complication after lumbar fusion. Risk factors for infectious complications after lumbar fusion have not been investigated using select set of SLLF procedures. METHODS: Patients who underwent SLLF between 2006 and 2011 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Multivariate logistic regression analyses were performed to identify pre- and intraoperative risk factors associated with postoperative infection. RESULTS: A total of 3353 patients were analyzed in this study. Overall, 173 (5.2%) patients experienced a postoperative infection, including 86 (2.6%) surgical site infections (SSIs) and 111 (3.3%) non-SSI infectious complications (pneumonia, urinary tract infection, sepsis/septic shock). Twenty-four (0.7%) patients experienced both SSI and non-SSI infectious complications. Postoperative SSI were associated with obesity (odds ratio [OR], 1.628; 95% confidence interval [CI], 1.042-2.544), American Society of Anesthesiologists class more than 2 (OR, 2.078; 95% CI, 1.309-3.299), and operative time more than 6 hours (OR, 2.573; 95% CI, 1.310-5.056). Risk factors for non-SSI infectious complications included age (60-69 yr; OR, 3.279; 95% CI, 1.541-6.980; and ≥70 yr; OR, 3.348; 95% CI, 1.519-7.378), female sex (OR, 1.791; 95% CI, 1.183-2.711), creatinine more than 1.5 mg/dL (OR, 2.400; 95% CI, 1.138-5.062), American Society of Anesthesiologists class more than 2 (OR, 1.835; 95% CI, 1.177-2.860), and operative time more than 6 hours (OR, 3.563; 95% CI, 2.082-6.097). CONCLUSION: Across a wide study population, we identified that obesity, advanced American Society of Anesthesiologists classification, and longer operative time were predictive of postoperative SSI. We also demonstrated that increased age, female sex, serum creatinine more than 1.5 mg/dL, and prolonged operative duration are associated with non-SSI infectious complications after SLLF. Continued efforts to elucidate and optimize perioperative risk factors are warranted to improve outcomes in patients requiring spinal fusion. LEVEL OF EVIDENCE: 3.

Electrostatics, structure prediction, and the energy landscapes for protein folding and binding.

While being long in range and therefore weakly specific, electrostatic interactions are able to modulate the stability and folding landscapes of some proteins. The relevance of electrostatic forces for steering the docking of proteins to each other is widely acknowledged, however, the role of electrostatics in establishing specifically funneled landscapes and their relevance for protein structure prediction are still not clear. By introducing Debye-Hückel potentials that mimic long-range electrostatic forces into the Associative memory, Water mediated, Structure, and Energy Model (AWSEM), a transferable protein model capable of predicting tertiary structures, we assess the effects of electrostatics on the landscapes of thirteen monomeric proteins and four dimers. For the monomers, we find that adding electrostatic interactions does not improve structure prediction. Simulations of ribosomal protein S6 show, however, that folding stability depends monotonically on electrostatic strength. The trend in predicted melting temperatures of the S6 variants agrees with experimental observations. Electrostatic effects can play a range of roles in binding. The binding of the protein complex KIX-pKID is largely assisted by electrostatic interactions, which provide direct charge-charge stabilization of the native state and contribute to the funneling of the binding landscape. In contrast, for several other proteins, including the DNA-binding protein FIS, electrostatics causes frustration in the DNA-binding region, which favors its binding with DNA but not with its protein partner. This study highlights the importance of long-range electrostatics in functional responses to problems where proteins interact with their charged partners, such as DNA, RNA, as well as membranes.

Preoperative Albumin Alone is Not a Predictor of 30-Day Outcomes in Pressure Ulcer Patients: A Matched Propensity-Score Analysis of the 2006-2011 NSQIP Datasets.

BACKGROUND: While there has been a great deal of literature describing the relationship between nutritional status and development of pressure ulcers, statistically rigorous studies analyzing the relationship between hypoalbuminemia and outcomes are lacking. METHODS: The American College of Surgeons' multicenter, prospective, National Surgical Quality Improvement Program database was used to identify patients who underwent surgery for treatment of pressure ulcers between 2006 and 2011. Matched propensity-score analysis was performed to match experimental groups with regard to preoperative comorbidities. Outcomes of interest included overall/surgical/medical complications and 30-day mortality. Multivariable logistic regression models were used to assess the independent association between hypoalbuminemia and outcomes. RESULTS: Over the 6-year study period, 551 patients met criteria for study inclusion. Median albumin level was 2.8 g/dL. Before propensity matching, multiple adverse outcomes were significantly elevated in patients with albumin levels below the median value (very-low albumin, or VLA), compared to control patients. However, after matching preoperative comorbidities, the differences in 30-day outcomes were eliminated. In both analyses, there was no significant difference in 30-day surgical complications. CONCLUSIONS: It is generally understood that hypoalbuminemic patients have elevated risks for surgical procedures. In pressure ulcer patients, it appears that these risks are not due to hypoalbuminemia alone, but rather a long list of attendant comorbidities. Consequently, hypoalbuminemia alone should not be used to determine the timing of a procedure for pressure ulcer surgery. Knowledge of these risks is necessary for patient counseling and surgical planning in this population.

Impact of resident involvement in neurosurgery: an analysis of 8748 patients from the 2011 American College of Surgeons National Surgical Quality Improvement Program database.

OBJECT: This study evaluates the impact of resident presence in the operating room on postoperative outcomes in neurosurgery. METHODS: The authors retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and identified all cases treated in a neurosurgery service in 2011. Propensity scoring analysis and multiple logistic regression models were used to reduce patient bias and to assess independent effect of resident involvement. RESULTS: Of the 8748 neurosurgery cases identified, residents were present in 4529 cases. Residents were more likely to be involved in complex procedures with longer operative duration. The multivariate analysis found that resident involvement was not a statistically significant factor for overall complications (OR 1.116, 95% CI 0.961-1.297), surgical complications (OR 1.132, 95% CI 0.825-1.554), medical complications (OR 1.146, 95% CI 0.979-1.343), reoperation (OR 1.250, 95% CI 0.984-1.589), mortality (OR 1.164, 95% CI 0.780-1.737), or unplanned readmission (OR 1.148, 95% CI 0.946-1.393). CONCLUSIONS: In this multicenter study, the authors demonstrated that resident involvement in the operating room was not a significant factor for postoperative complications in neurosurgery service. This analysis also showed that much of the observed difference in postoperative complication rates was attributable to other confounding factors. This is a quality indicator for resident trainees and current medical education. Maintaining high standards in postgraduate training is imperative in enhancing patient care and reducing postoperative complications.

Predictive energy landscapes for folding membrane protein assemblies.

We study the energy landscapes for membrane protein oligomerization using the Associative memory, Water mediated, Structure and Energy Model with an implicit membrane potential (AWSEM-membrane), a coarse-grained molecular dynamics model previously optimized under the assumption that the energy landscapes for folding α-helical membrane protein monomers are funneled once their native topology within the membrane is established. In this study we show that the AWSEM-membrane force field is able to sample near native binding interfaces of several oligomeric systems. By predicting candidate structures using simulated annealing, we further show that degeneracies in predicting structures of membrane protein monomers are generally resolved in the folding of the higher order assemblies as is the case in the assemblies of both nicotinic acetylcholine receptor and V-type Na(+)-ATPase dimers. The physics of the phenomenon resembles domain swapping, which is consistent with the landscape following the principle of minimal frustration. We revisit also the classic Khorana study of the reconstitution of bacteriorhodopsin from its fragments, which is the close analogue of the early Anfinsen experiment on globular proteins. Here, we show the retinal cofactor likely plays a major role in selecting the final functional assembly.

Predictors of 61 unplanned readmission cases in microvascular free tissue transfer patients: multi-institutional analysis of 774 patients.

BACKGROUND: Unplanned readmissions serve as a marker for health care quality. Risk factors associated with unplanned readmission after microvascular free tissue transfer have never been examined. In this study, we sought to identify perioperative predictors of 30-day unplanned readmission in free flap patients. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed to identify all patients who underwent microvascular free tissue transfer in 2011. Multivariate logistic regression models were used to estimate independent predictors of unplanned readmission. RESULTS: Among free flap patients, unplanned readmission rate was 7.9%. In multivariate analysis, the only factor that significantly predicted unplanned readmission (P < 0.05) was open wound/wound infection (odds ratio [OR] 2.71). Postoperative variables significantly associated with unplanned readmission included surgical complications (OR 5.43), medical complications (OR 5.62), and unplanned reoperation (OR 3.94). Flap failure was not associated with unplanned readmission. CONCLUSIONS: In our study, the presence of either open wound/wound infection, development of surgical complications, medical complications, and unplanned reoperations were associated with unplanned readmissions. Further research in predictive factors is suggested to avoid costly, unnecessary, and preventable readmissions.

Predictors of adverse events after parotidectomy: a review of 2919 cases.

OBJECTIVE: There is a current paucity of large-scale, multi-institutional studies that explore the risk factors for major complications following parotidectomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program participant use file was reviewed to identify all patients who had undergone parotidectomy between 2006 and 2011. Risk factors that predicted adverse events were estimated by using multivariate logistic regression. RESULTS: Of 2919 included patients, 202 patients experienced adverse outcomes within the first 30 days of surgery. These included surgical complications in 76 (2.6%) patients; medical complications in 90 (3.1%) patients; death in 7 (0.2%) patients; and reoperation in 77 (2.6%) patients. Predictors of any complication included disseminated cancer (odds ratio [OR] = 2.28; 95% confidence interval [CI], 1.05-4.95; P = .036) and increasing total relative value units (OR = 1.01; 95% CI, 1.00-1.02; P = .027). Active smoking was a major risk factor for surgical complications (OR = 1.81; 95% CI, 1.08-3.05; P = .025). Dyspnea (OR = 2.93; 95% CI, 1.37-6.27; P = .006) significantly predicted medical complications. CONCLUSION: Although complication rates after parotidectomy are generally low, avoidance of specific and nonspecific postoperative complications still remains an area for improvement. Future outcomes databases should include procedure-specific complications, including facial nerve injury.

Preoperative anemia does not predict complications after single-level lumbar fusion: a propensity score-matched multicenter study.

STUDY DESIGN: Multicenter retrospective cohort study. OBJECTIVE: To estimate the impact of preoperative anemia on 30-day complications in patients undergoing single-level lumbar fusion. SUMMARY OF BACKGROUND DATA: Anemia has been widely implicated as a risk factor in various surgical procedures including elective spine surgery. No large-scale study has been performed to examine this relationship in single-level lumbar fusion surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was retrospectively reviewed to identify all patients who underwent single-level lumbar fusion procedures during 2006 to 2011. A propensity score-matching algorithm was used to match scores of anemic patients with that of nonanemic patients. Multivariate logistic regression analysis of unadjusted and propensity score-matched cohorts was performed to examine the effect of preoperative anemia on 30-day postoperative complication rates and length of hospital stay. RESULTS: A total of 2960 patients met inclusion criteria. The propensity score-matching procedure yielded scores of 491 pairs of well-matched nonanemic and anemic patients. The multivariate analysis of propensity score-matched population found preoperative anemia to carry no significant association with any of the complications analyzed, including overall complications, medical complications, surgical complications, reoperation, mortality, or length of total hospital stay. CONCLUSION: For patients undergoing single-level lumbar fusion, preoperative anemia is not independently associated with increased risk of 30-day complications or increased length of stay. Further studies are needed to independently validate this relationship in other spine surgical procedures. LEVEL OF EVIDENCE: 3.

Predictive energy landscapes for folding α-helical transmembrane proteins.

We explore the hypothesis that the folding landscapes of membrane proteins are funneled once the proteins' topology within the membrane is established. We extend a protein folding model, the associative memory, water-mediated, structure, and energy model (AWSEM) by adding an implicit membrane potential and reoptimizing the force field to account for the differing nature of the interactions that stabilize proteins within lipid membranes, yielding a model that we call AWSEM-membrane. Once the protein topology is set in the membrane, hydrophobic attractions play a lesser role in finding the native structure, whereas polar-polar attractions are more important than for globular proteins. We examine both the quality of predictions made with AWSEM-membrane when accurate knowledge of the topology and secondary structure is available and the quality of predictions made without such knowledge, instead using bioinformatically inferred topology and secondary structure based on sequence alone. When no major errors are made by the bioinformatic methods used to assign the topology of the transmembrane helices, these two types of structure predictions yield roughly equivalent quality structures. Although the predictive energy landscape is transferable and not structure based, within the correct topological sector we find the landscape is indeed very funneled: Thermodynamic landscape analysis indicates that both the total potential energy and the contact energy decrease as native contacts are formed. Nevertheless the near symmetry of different helical packings with respect to native contact formation can result in multiple packings with nearly equal thermodynamic occupancy, especially at temperatures just below collapse.

Spine surgeon specialty is not a risk factor for 30-day complication rates in single-level lumbar fusion: a propensity score-matched study of 2528 patients.

STUDY DESIGN: Multicenter retrospective cohort study. OBJECTIVE: To investigate the impact of spine surgeon specialty on 30-day complication rates in patients undergoing single-level lumbar fusion. SUMMARY OF BACKGROUND DATA: Operative care of the spine is delivered by surgeons who undergo either orthopedic or neurosurgical training. It is currently unknown whether surgeon specialty has an impact on 30-day complication rates in patients undergoing single-level lumbar fusion. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was retrospectively reviewed to identify all patients who underwent single-level lumbar fusion procedures during 2006-2011. Propensity score matching analysis was employed to reduce baseline differences in patient characteristics. Univariate and multivariate analyses were performed to assess the impact of spine surgeon specialty on 30-day complication rates. RESULTS: A total of 2970 patients were included for analysis. After propensity matching, 1264 pairs of well-matched patients remained in the cohort. Overall complication rates in the unadjusted data set were 7.3% and 7.1% for the neurosurgery and orthopedic surgery cohort, respectively. Our multivariate analysis revealed that compared with the neurosurgery cohort, the orthopedic surgery cohort did not have statistically significant differences in odds ratios (OR) for development of any complication (OR, 0.95; 95% confidence interval [CI], 0.69-1.30; P = 0.740). Similarly, spine surgeon specialty was not a risk factor in any of the specific complications studied, including medical complications (OR, 1.11; 95% CI, 0.77-1.60; P = 0.583), surgical complications (OR, 0.76; 95% CI, 0.46-1.26; P = 0.287), or reoperation (OR, 1.10; 95% CI, 0.76-1.60; P = 0.618). CONCLUSION: Our analysis demonstrates that spine surgeon specialty is not a risk factor for any of the reported 30-day complications in patients undergoing single-level lumbar fusion. These data support the currently dichotomous paradigm of training for spine surgeons. Further research is warranted to validate this relationship in other spine procedures and for other outcomes. LEVEL OF EVIDENCE: 4.

Use of recombinant factor VIIa (rFVIIa) as pre-hospital treatment in a swine model of fluid percussion traumatic brain injury.

CONTEXT: Recombinant factor VIIa (rFVIIa) has been used as an adjunctive therapy for acute post-traumatic hemorrhage and reversal of iatrogenic coagulopathy in trauma patients in the hospital setting. However, investigations regarding its potential use in pre-hospital management of traumatic brain injury (TBI) have not been conducted extensively. AIMS: In the present study, we investigated the physiology, hematology and histology effects of a single pre-hospital bolus injection of rFVIIa compared to current clinical practice of no pre-hospital intervention in a swine model of moderate fluid percussion TBI. MATERIALS AND METHODS: Animals were randomized to receive either a bolus of rFVIIa (90 µg/kg) or nothing 15 minutes (T15) post-injury. Hospital arrival was simulated at T60, and animals were euthanized at experimental endpoint (T360). RESULTS: Survival was 100% in both groups; baseline physiology parameters were similar, vital signs were comparable. Animals that received rFVIIa demonstrated less hemorrhage in subarachnoid space (P = 0.0037) and less neuronal degeneration in left hippocampus, pons, and cerebellum (P = 0.00009, P = 0.00008, and P = 0.251, respectively). Immunohistochemical staining of brain sections showed less overall loss of microtubule-associated protein 2 (MAP2) and less Flouro-Jade B positive cells in rFVIIa-treated animals. CONCLUSIONS: Early pre-hospital administration of rFVIIa in this swine TBI model reduced neuronal necrosis and intracranial hemorrhage (ICH). These results merit further investigation of this approach in pre-hospital trauma care.

Predictors of unplanned readmission in patients undergoing lumbar decompression: multi-institutional analysis of 7016 patients.

OBJECT: Unplanned hospital readmission represents a large financial burden on the Centers for Medicare and Medicaid Services, commercial insurance payers, hospitals, and individual patients, and is a principal target for cost reduction. A large-scale, multi-institutional study that evaluates risk factors for readmission has not been previously performed in patients undergoing lumbar decompression procedures. The goal of this multicenter retrospective study was to find preoperative, intraoperative, and postoperative predictive factors that result in unplanned readmission (UR) after lumbar decompression surgery. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed to identify all patients who received lumbar decompression procedures in 2011. Risk-adjusted multivariate logistic regression analysis was performed to estimate independent predictors of UR. RESULTS: The overall rate of UR among patients undergoing lumbar decompression was 4.4%. After multivariate logistic regression analysis, anemia (odds ratio [OR] 1.48), dependent functional status (OR 3.03), total operative duration (OR 1.003), and American Society of Anesthesiologists Physical Status Class 4 (OR 3.61) remained as independent predictors of UR. Postoperative complications that were significantly associated with UR included overall complications (OR 5.18), pulmonary embolism (OR 3.72), and unplanned reoperation (OR 56.91). CONCLUSIONS: There were several risk factors for UR after lumbar spine decompression surgery. Identification of high-risk patients and appropriate allocation of resources to reduce postoperative incidence may reduce the readmission rate.

Operative duration as an independent risk factor for postoperative complications in single-level lumbar fusion: an analysis of 4588 surgical cases.

STUDY DESIGN: Multicenter retrospective cohort study. OBJECTIVE: To estimate the impact of increasing surgical duration on outcomes after single-level lumbar fusion. SUMMARY OF BACKGROUND DATA: Lumbar fusion is a widely used practice for the treatment of disability and chronic low back pain. Longer operative duration is shown to correlate with increased morbidity and mortality in various surgical disciplines, but no large-scale study has been performed to validate this relationship in lumbar spine surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was retrospectively reviewed to identify all patients who underwent lumbar fusion procedures during 2006 to 2011. Thirty-day morbidity and mortality rates were reported on the basis of operative time, whereas multivariate logistic regression model was used to examine operative duration as an independent risk factor for outcomes. RESULTS: A total of 4588 patients were included in the analysis. The mean operative duration for all patients was 197 ± 105 minutes. Our multivariate risk-adjusted regression models demonstrated that increasing operative time was associated with step-wise increase in risk for overall complications (odds ratio [OR], 2.09-5.73), medical complications (OR, 2.18-6.21), surgical complications (OR, 1.65-2.90), superficial surgical site infection (OR, 2.65-3.97), and postoperative transfusions (OR, 3.25-12.19). Operative duration of 5 hours or more was also associated with increased risk of reoperation (OR, 2.17), organ/space surgical site infection (OR, 9.72), sepsis/septic shock (OR, 4.41), wound dehiscence (OR, 10.98), and deep vein thrombosis (OR, 17.22). CONCLUSION: Our data suggest that increasing operative duration is associated with a wide array of complications. Operative duration is, therefore, an important quality metric in the performance of lumbar fusion. Strategies to reduce operative time and further research to identify risk factors that are associated with longer surgical duration are needed for improved patient outcomes. LEVEL OF EVIDENCE: 3.

Blind endovascular catheterization and direct access of an occluded superior ophthalmic vein for treatment of carotid cavernous fistula.

We describe a case of an elderly patient who presented with right-sided ophthalmoplegia, proptosis, chemosis, and increased intraocular pressure. An angiogram showed feeding vessels from the bilateral internal and external carotid arteries. Our initial attempt to blindly probe the inferior petrosal sinus was unsuccessful. This was followed by a right anterior orbitotomy exposing the superior ophthalmic vein which was directly cannulated with an 18 gauge angiocatheter. However, a proximal third of the superior ophthalmic vein within the orbit which was thrombosed was probed blindly. The thrombosed vein was cannulated with a microcatheter to obtain coil embolization of the carotid cavernous fistula. The implications of the procedure are discussed, given that, to our knowledge, such an endeavor has never been performed.

Intraoperative transfusion of packed red blood cells in microvascular free tissue transfer patients: assessment of 30-day morbidity using the NSQIP dataset.

Although often a life-saving therapeutic maneuver, there is minimal data available that details the effects of intraoperative packed red blood cell transfusion (IOT) after microvascular free tissue transfer. The National Surgical Quality Improvement Program database was queried to identify all patients who underwent microvascular free tissue transfer between 2006 and 2010. Multivariate logistic regression models were used to determine the association between intraoperative transfusion and outcomes. Upon bivariate and multivariate analyses, IOT was significantly associated with higher rates of overall complications (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.12-3.63), medical complications (OR, 3.35; 95% CI, 1.75-6.42), postoperative transfusion (OR, 6.02; 95% CI, 2.02-17.97), and reoperation (OR, 2.24; 95% CI, 1.24-4.04). IOT was not associated with either surgical complications or free flap loss. IOT significantly increases risk for adverse overall and medical complications. However, IOT was not associated with surgical complications or free flap loss. Transfusion practices in the operating room should be reevaluated to improve overall outcomes.

Predictors of thirty-day readmission after anterior cervical fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the incidence of and factors predicting 30-day readmission after anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is being performed on an increasing basis on a wider population of patients, which is accompanied by rising costs. Readmissions have the potential to further deplete health care resources. Although past studies have shown that readmissions after surgery are driven by operative complications, specific predictors of readmission after ACDF are not well researched. METHODS: All patients who underwent ACDF or anterior corpectomy and fusion procedures in 2011 were selected from the American College of Surgeon's National Quality Improvement database. Readmissions were analyzed on the basis of demographics, comorbidities, operative characteristics, and complications were compared in univariate analyses. Multivariate logistic regression models were created to isolate the independent effects of preoperative and postoperative factors on readmission. RESULTS: The nationwide readmission rate after ACDF surgery in this study is 2.5%. Pulmonary complications (8.5%), wound complications (8.5%), and urinary tract infections (8.5%) are the most common complications seen in readmitted patients. Readmitted patients were significantly older (58 vs. 53, P = 0.003), with higher rates of diabetes and hypertension (28.8% vs. 13.9%, P = 0.001; 64.4% vs. 42.6%, P = 0.001, respectively). Although certain preoperative factors such as age 65 years or more and preoperative stay more than 24 hours increase the odds of operative complications (odds ratio, 3.5; 95% confidence interval, 2.0-6.0 and odds ratio, 6.2; 95% confidence interval, 3.4-11.1, respectively), hypertension may independently increase the likelihood of readmission outside of any effect on complications (odds ratio, 1.8; 95% confidence interval, 1.0-3.4). CONCLUSION: The data in this study suggests that surgeons are already controlling readmission rates by limiting peri- and postoperative complications, but patients with a history of hypertension could have an increased likelihood of being readmitted despite avoiding a complication. LEVEL OF EVIDENCE: 3.

Anesthesia duration as an independent risk factor for postoperative complications in free flap surgery: a review of 1,305 surgical cases.

Surgical dogma and objective data support the relationship between increased operative times and perioperative complications. However, there has been no large-scale, multi-institutional study that evaluates the impact of increased anesthesia duration on microvascular free tissue transfer. The National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed to identify all free-flap patients between 2006 and 2011. Included patients were subdivided into quintiles of anesthesia time. Univariate and multivariate analyses were performed to assess its impact on 30-day postoperative complications. The mean anesthesia duration for all patients was 603 ± 222 minutes. In univariate analysis, 30-day overall/medical complications, reoperation, and free flap loss demonstrated statistically significant increases as anesthesia duration increased (p<0.05). However, in multivariate analyses, these trends and significances were abolished, with exception of the utilization of postoperative transfusions. Of interest, increasing anesthesia duration did not predict flap failure on multivariate analysis. We found that increased anesthesia time correlates with increased postoperative transfusions in free flap patients. As a result, limiting blood loss and avoiding prolonged anesthesia times should be goals for the microvascular surgeon. This is the largest multidisciplinary study to investigate the ongoing debate that longer anesthesia times impart greater risk.

Funneling and frustration in the energy landscapes of some designed and simplified proteins.

We explore the similarities and differences between the energy landscapes of proteins that have been selected by nature and those of some proteins designed by humans. Natural proteins have evolved to function as well as fold, and this is a source of energetic frustration. The sequence of Top7, on the other hand, was designed with architecture alone in mind using only native state stability as the optimization criterion. Its topology had not previously been observed in nature. Experimental studies show that the folding kinetics of Top7 is more complex than the kinetics of folding of otherwise comparable naturally occurring proteins. In this paper, we use structure prediction tools, frustration analysis, and free energy profiles to illustrate the folding landscapes of Top7 and two other proteins designed by Takada. We use both perfectly funneled (structure-based) and predictive (transferable) models to gain insight into the role of topological versus energetic frustration in these systems and show how they differ from those found for natural proteins. We also study how robust the folding of these designs would be to the simplification of the sequences using fewer amino acid types. Simplification using a five amino acid type code results in comparable quality of structure prediction to the full sequence in some cases, while the two-letter simplification scheme dramatically reduces the quality of structure prediction.

Blind endovascular catheterization and direct access of an occluded superior ophthalmic vein for treatment of carotid cavernous fistula.

We describe a case of an elderly patient who presented with right-sided ophthalmoplegia, proptosis, chemosis, and increased intraocular pressure. An angiogram showed feeding vessels from the bilateral internal and external carotid arteries. Our initial attempt to blindly probe the inferior petrosal sinus was unsuccessful. This was followed by a right anterior orbitotomy exposing the superior ophthalmic vein which was directly cannulated with an 18 gauge angiocatheter. However, a proximal third of the superior ophthalmic vein within the orbit which was thrombosed was probed blindly. The thrombosed vein was cannulated with a microcatheter to obtain coil embolization of the carotid cavernous fistula. The implications of the procedure are discussed, given that, to our knowledge, such an endeavor has never been performed.

Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: an exploratory study in a swine controlled haemorrhage model.

BACKGROUND: Vasoconstriction is a side effect that may prevent the use of haemoglobin based oxygen carrier (HBOC) as blood substitute. Therefore, we tested the hypothesis that the NO donor, sodium nitroprusside (SNP), would mitigate systemic and pulmonary hypertension associated with HBOC-201 in a simple controlled haemorrhage swine model. METHODS: After 55% estimated blood volume withdrawal through a venous catheter, invasively anesthetized and instrumented animals were resuscitated with three 10 ml/kg infusions of either HBOC-201 or Hextend (HEX) with or without 0.8 µg/kg/min SNP (infused concomitantly via different lines). Haemodynamics, direct and indirect measures of tissue oxygenation, and coagulation were measured for 2h. RESULTS: Haemorrhage caused a state of shock manifested by hypotension and base deficit. HBOC-201 resuscitation resulted in higher systemic (p<0.0001) and pulmonary (p<0.002) blood pressure than with HEX. Elevation of systemic (p<0.0001) but not pulmonary (p>0.05) arterial pressure was attenuated by co-infusion of SNP, without significant group differences in haemodynamics, tissue oxygenation, platelet function, coagulation, methaemoglobin, or survival (p>0.05). CONCLUSION: In swine with haemorrhagic shock, co-administration of the NO donor, SNP, effectively and safely reduces HBOC-201-related systemic but not pulmonary vasoactivity. Interestingly, co-administration of the vasodilator SNP with HEX had no deleterious effects in comparison with HEX alone.