Plasma Environment, Radiation, Structure, and Evolution of the Uranian System (PERSEUS): A Dedicated Orbiter Mission Concept to Study Space Physics at Uranus.

The Plasma Environment, Radiation, Structure, and Evolution of the Uranian System (PERSEUS) mission concept defines the feasibility and potential scope of a dedicated, standalone Heliophysics orbiter mission to study multiple space physics science objectives at Uranus. Uranus's complex and dynamic magnetosphere presents a unique laboratory to study magnetospheric physics as well as its coupling to the solar wind and the planet's atmosphere, satellites, and rings. From the planet's tilted and offset, rapidly-rotating non-dipolar magnetic field to its seasonally-extreme interactions with the solar wind to its unexpectedly intense electron radiation belts, Uranus hosts a range of outstanding and compelling mysteries relevant to the space physics community. While the exploration of planets other than Earth has largely fallen within the purview of NASA's Planetary Science Division, many targets, like Uranus, also hold immense scientific value and interest to NASA's Heliophysics Division. Exploring and understanding Uranus's magnetosphere is critical to make fundamental gains in magnetospheric physics and the understanding of potential exoplanetary systems and to test the validity of our knowledge of magnetospheric dynamics, moon-magnetosphere interactions, magnetosphere-ionosphere coupling, and solar wind-planetary coupling. The PERSEUS mission concept study, currently at Concept Maturity Level (CML) 4, comprises a feasible payload that provides closure to a range of space physics science objectives in a reliable and mature spacecraft and mission design architecture. The mission is able to close using only a single Mod-1 Next-Generation Radioisotope Thermoelectric Generator (NG-RTG) by leveraging a concept of operations that relies of a significant hibernation mode for a large portion of its 22-day orbit.

Complete blood platelet and lymphocyte ratios increase diagnostic accuracy of periprosthetic joint infection following total hip arthroplasty.

INTRODUCTION: Systemically, changes in serum platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte (MLR) represent primary responses to early inflammation and infection. This study aimed to determine whether PLR, PVR, NLR, and MLR can be useful in diagnosing periprosthetic joint infection (PJI) in total hip arthroplasty (THA) patients. METHODS: A total of 464 patients that underwent revision THA with calculable PLR, PVR, NLR, and MLR in 2 groups was evaluated: 1) 191 patients with a pre-operative diagnosis of PJI, and 2) 273 matched patients treated for revision THA for aseptic complications. RESULTS: The sensitivity and specificity of PLR combined with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial white blood cell count (WBC) and synovial polymorphonuclear leukocytes (PMN) (97.9%; 98.5%) is significantly higher than only ESR combined with CRP, synovial WBC and synovial PMN (94.2%; 94.5%; p < 0.01). The sensitivity and specificity of PVR combined with ESR, CRP and synovial WBC, and synovial PMN (98.4%; 98.2%) is higher than only ESR combined with CRP, synovial WBC and synovial PMN (94.2%; 94.5%; p < 0.01). CONCLUSION: The study results demonstrate that both PLR and PVR calculated from complete blood counts when combined with serum and synovial fluid markers have increased diagnostic sensitivity and specificity in diagnosing periprosthetic joint infection in THA patients. LEVEL OF EVIDENCE: III, case-control retrospective analysis.

Elevated ESR and CRP Prior to Second-Stage Reimplantation Knee Revision Surgery for Periprosthetic Joint Infection Are Associated with Increased Reinfection Rates.

Although two-stage revision surgery is considered as the most effective treatment for managing chronic periprosthetic joint infection (PJI), there is no current consensus on the predictors of optimal timing to second-stage reimplantation. This study aimed to compare clinical outcomes between patients with elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior to second-stage reimplantation and those with normalized ESR and CRP prior to second-stage reimplantation. We retrospectively reviewed 198 patients treated with two-stage revision total knee arthroplasty for chronic PJI. Cohorts included patients with: (1) normal level of serum ESR and CRP (n = 96) and (2) elevated level of serum ESR and CRP prior to second-stage reimplantation (n = 102). Outcomes including reinfection rates and readmission rates were compared between both cohorts. At a mean follow-up of 4.4 years (2.8-6.5 years), the elevated ESR and CRP cohort demonstrated significantly higher reinfection rates compared with patients with normalized ESR and CRP prior to second-stage reimplantation (33.3% vs. 14.5%, p < 0.01). Patients with both elevated ESR and CRP demonstrated significantly higher reinfection rates, when compared with patients with elevated ESR and normalized CRP (33.3% vs. 27.6%, p = 0.02) as well as normalized ESR and elevated CRP (33.3% vs. 26.3%, p < 0.01). This study demonstrates that elevated serum ESR and/or CRP levels prior to reimplantation in two-stage knee revision surgery for chronic PJI are associated with increased reinfection rate after surgery. Elevation of both ESR and CRP were associated with a higher risk of reinfection compared with elevation of either ESR or CRP, suggesting the potential benefits of normalizing ESR and CRP prior to reimplantation in treatment of chronic PJI.

The Effect of Joint Line Elevation on In Vivo Knee Kinematics in Bicruciate Retaining Total Knee Arthroplasty.

Prior studies have reported a negative effect on both clinical outcomes and patient-reported outcome measures (PROMS) following joint line elevation (JLE) in cruciate-retaining (CR) total knee arthroplasty (TKA) and posterior stabilized (PS) TKA designs. This experimental study was aimed to quantify the effect of JLE on in vivo knee kinematics in patients with bicruciate retaining (BCR) TKA during strenuous activities. Thirty unilateral BCR TKA patients were evaluated during single-leg deep lunge and sit-to-stand using a validated combined computer tomography and dual fluoroscopic imaging system. Correlation analysis was performed to quantify any correlations between JLE and in vivo kinematics, as well as PROMS. There was a significant negative correlation between JLE and maximum flexion angle during single-leg deep lunge (ρ = -0.34, p = 0.02), maximum varus joint angles during single-leg deep lunge (ρ = -0.37, p = 0.04), and sit-to-stand (ρ = -0.29, p = 0.05). There was a significant negative correlation between JLE and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (ρ = -0.39, p = 0.01) and knee disability and osteoarthritis outcome score physical function (KOOS-PS; ρ = -0.33, p = 0.03). The JLE that yields a significant loss in PROMS and maximum flexion angles were 2.6 and 2.3 mm, respectively. There was a linear negative correlation of JLE with both in vivo knee kinematics and PROMS, with changes in JLE of greater than 2.6 and 2.3 mm, leading to a clinically significant loss in PROMS and maximum flexion angles, respectively, suggesting an increased need to improve surgical precision to optimize patient outcomes following BCR TKA.

Gait and Knee Flexion In Vivo Kinematics of Asymmetric Tibial Polyethylene Geometry Cruciate Retaining Total Knee Arthroplasty.

The preservation of the posterior cruciate ligament in cruciate retaining (CR) total knee arthroplasty (TKA) designs has the potential to restore healthy knee biomechanics; however, concerns related to kinematic asymmetries during functional activities still exist in unilateral TKA patients. As there is a limited data available regarding the ability of the contemporary CR TKA design with concave medial and convex lateral tibial polyethylene bearing components to restore healthy knee biomechanics, this study aimed to investigate in vivo three-dimensional knee kinematics in CR TKA patients during strenuous knee flexion activities and gait. Using a combined computer tomography and dual fluoroscopic imaging system approach, in vivo kinematics of 15 unilateral CR TKA patients (comparison of replaced and contralateral nonreplaced knee) were evaluated during sit-to-stand, step-ups, single-leg deep lunge, and level walking. The patient cohort was followed-up at an average of 24.5 months ( ± 12.6, range 13-42) from surgical procedure. Significantly smaller internal knee rotation angles were observed for the contemporary CR TKA design during step-ups (2.6 ± 5.8 vs. 6.3 ± 6.6 degrees, p < 0.05) and gait (0.6 ± 4.6 vs. 6.3 ± 6.8 degrees, p < 0.05). Significantly larger proximal and anterior femoral translations were measured during sit-to-stand (34.7 ± 4.5 vs. 29.9 ± 3.1 mm, p < 0.05; -2.5 ± 2.9 vs. -8.1 ± 4.4 mm, p < 0.05) and step-ups (34.1 ± 4.5 vs. 30.8 ± 2.9 mm, p < 0.05; 2.2 ± 3.2 vs. -3.5 ± 4.5 mm, p < 0.05). Significantly smaller ranges of varus/valgus and internal/external rotation range of motion were observed for CR TKA, when compared with the nonoperated nee, during strenuous activities and gait. The preservation of the posterior cruciate ligament in the contemporary asymmetric bearing geometry CR TKA design with concave medial and convex lateral tibial polyethylene bearing components has the potential to restore healthy knee biomechanics; however, the study findings demonstrate that native knee kinematics were not fully restored in patients with unilateral asymmetric tibial polyethylene bearing geometry CR TKA during functional activities.

Outcomes and Risk Factors Associated With Failures of Debridement, Antibiotics, and Implant Retention in Patients With Acute Hematogenous Periprosthetic Joint Infection.

BACKGROUND: Acute hematogenous periprosthetic joint infections (PJI) accounts for 20% to 35% of all PJI cases. Treatment options include débridement, antibiotics, and implant retention (DAIR) or implant revision (single-stage/two-stage revision). Because the reported success rates of DAIR for acute PJIs as reported in the literature varies widely, this study aimed to investigate (1) the outcome of DAIR as revision surgery procedure and (2) the potential risk factors for treatment failure of DAIR in patients with acute hematogenous PJI. METHODS: We reviewed 106 consecutive cases of total joint arthroplasty patients who underwent DAIR for the diagnosis of acute hematogenous PJI. Outcomes of the cohort including infection free survival was investigated. Mean follow-up was 4.9 years. Demographics, case data, comorbidities, and extremity score were analyzed by univariate and multivariate regressions to identify risk factors for failure of DAIR. RESULTS: The failure rate of patients who underwent DAIR was 23.6% (25 of 106 patients). Univariate regression demonstrated that diabetes mellitus (P = 0.01) and polymicrobial infections (P < 0.01) are associated with failure of DAIR. Multivariate regression confirmed diabetes mellitus and polymicrobial infections as independent risk factors for failure of DAIR. DISCUSSION: Debridement, antibiotics, and implant retention may be a viable treatment option with moderate failure rates at the midterm follow-up in cases of acute hematogenous PJI. The study also identified diabetes mellitus and polymicrobial infections as independent risk factors for failure of DAIR. The findings of this study provide clinically useful information for surgeons in treatment of patients with acute hematogenous PJI.

Development of a Preoperative Risk Calculator for Reinfection Following Revision Surgery for Periprosthetic Joint Infection.

BACKGROUND: A recent systematic review demonstrated that reinfection rates following eradication of hip and knee periprosthetic joint infection (PJI) may be as high as 29%. This study aimed to develop a preoperative risk calculator for assessing patient's individual risk associated with reinfection following treatment of PJI in total joint arthroplasty (TJA). METHODS: A total of 1081 consecutive patients who underwent revision TJA for PJI were evaluated. In total, 293 patients were diagnosed with TJA reinfection. A total of 56 risk factors, including patient characteristics and surgical variables, were evaluated with multivariate regression analysis. Analysis of the area under the receiver operating characteristics curve was performed to evaluate the strength of the predictive model. RESULTS: Of the 56 risk factors studied, 19 were found to have a significant effect as risk factor for TJA reinfection. The strongest predictors for TJA reinfection included previous PJI treatment techniques such as irrigation and debridement, the number of previous surgical interventions, medical comorbidities such as obesity, drug abuse, depression and smoking, as well as microbiology including the presence of Enterococcus species. The combined area under the receiver operating characteristics curve of the risk calculator for periprosthetic hip and knee joint reinfection was 0.75. CONCLUSIONS: The study findings demonstrate that surgical factors, including previous PJI surgical treatment techniques as well as the number of previous surgeries, alongside microbiology including the presence of Enterococcus species have the strongest effect on the risk for periprosthetic THA and TKA joint reinfection, suggesting the limited applicability of the existing risk calculators for the development of PJI following primary TJA in predicting the risk of periprosthetic joint reinfection.

Lumbar Spine Fusion Before Revision Total Hip Arthroplasty Is Associated With Increased Dislocation Rates.

BACKGROUND: The aim of this study was to determine whether timing of lumbar spinal fusion (LSF) before revision total hip arthroplasty (THA) would impact dislocation and rerevision rates. METHODS: This retrospective analysis includes a total of 505 patients who underwent revision THA with concomitant diagnosis of degenerative lumbar spinal stenosis with spondylolisthesis. Patients were stratified into the following two cohorts: (1) 328 patients who underwent revision THA with previous LSF and (2) 177 patients who underwent revision THA, followed by LSF. Postoperative complications including dislocation and rerevision rates were evaluated. RESULTS: Patients who underwent revision THA with previous LSF demonstrated significantly higher dislocation rates and rerevision rates compared with patients who underwent revision THA, followed by LSF, at the 1-year follow-up (6.7% versus 5.1%, P < 0.01; 8.5% versus 7.0%, P = 0.02). Patients who underwent revision THA, followed by LSF within 1 year demonstrated significantly higher dislocation and rerevision rates (5.6% versus 4.1%; 7.6% versus 6.4%). DISCUSSION: This study demonstrates that patients who underwent revision THA with previous LSF demonstrated notably higher dislocation rates and rerevision rates compared with patients who underwent revision THA, followed by LSF, with the greater the intervals between revision THA and LSF, the lower the postoperative dislocation rates and rerevision rates.

Outcomes and Risk Factors Associated With 2-Stage Reimplantation Requiring an Interim Spacer Exchange for Periprosthetic Joint Infection.

BACKGROUND: Patients undergoing a 2-stage revision for periprosthetic joint infection (PJI) often require a repeat spacer in the interim due to persistent infection. This study aims to report outcomes for patients with repeat spacer exchange and to identify risk factors associated with interim spacer exchange in 2-stage revision arthroplasty. METHODS: A total of 256 consecutive 2-stage revisions for chronic infection of total hip arthroplasty and total knee arthroplasty with reimplantation and minimum 2-year follow-up were investigated. An interim spacer exchange was performed in 49 patients (exchange cohort), and these patients were propensity score matched to 196 patients (nonexchange cohort). Multivariate analysis was performed to analyze risk factors for failure of interim spacer exchange. RESULTS: Patients in the propensity score-matched exchange cohort demonstrated a significantly increased reinfection risk compared to patients without interim spacer exchange (24% vs 15%, P = .03). Patients in the propensity score-matched exchange cohort showed significantly lower postoperative scores for 3 patient-reported outcome measures (PROMs): hip disability and osteoarthritis outcome score physical function (46.0 vs 54.9, P = .01); knee disability and osteoarthritis outcome score physical function (43.1 vs 51.7, P < .01); and patient-reported outcomes measurement information system physical function short form (41.6 vs 47.0, P = .03). Multivariate analysis demonstrated Charles Comorbidity Index (odds ratio, 1.56; P = .01) and the presence of Enterococcus species (odds ratio, 1.43; P = .03) as independent risk factors associated with 2-stage reimplantation requiring an interim spacer exchange for periprosthetic joint infection. CONCLUSION: This study demonstrates that patients with spacer exchange had a significantly higher risk of reinfection at 2 years of follow-up. Additionally, patients with spacer exchange demonstrated lower postoperative PROM scores and diminished improvement in multiple PROM scores after reimplantation, indicating that an interim spacer exchange in 2-stage revision is associated with worse patient outcomes.

MRI Characteristics of Adverse Local Tissue Reactions Associated With Intraoperative Tissue Damage and Poor Revision Surgery Outcomes: A Systematic Review.

BACKGROUND: Metal artifact reductions sequence (MARS) MRI has been established as a cross-sectional imaging modality for diagnosis of adverse local tissue reaction (ALTR). This study aims to evaluate the current literature regarding the characteristics of MARS MRI associated with intraoperative tissue necrosis and postoperative complications in patients undergoing revision THA because of ALTR. METHODS: We systematically searched the literature that included reporting MRI characteristics of ALTR in failed THA and their correlation with intraoperative findings and postoperative outcomes. RESULTS: A total of 617 studies were assessed, and 15 studies met the inclusion criteria. Synovial wall thickness correlated with increasing ALVAL grade, however, weakly with tissue necrosis. Synovial composition of mixed or solid features and the presence of abductor disruption correlated with complications and tissue necrosis. Tissue edema was a poor predictor of aseptic lymphocyte-dominant vasculitis-associated lesion (ALVAL) grade or tissue necrosis. DISCUSSION: MARS MRI synovial composition including mixed and solid features and the presence of abductor disruption provide the best prognostic characteristics associated with intraoperative soft-tissue necrosis and revision surgery outcome. These prognostic characteristics on MRI may assist surgeons with improved criteria for intervention and preoperative patient counseling.

Total knee arthroplasty following intramedullary tibial nailing.

INTRODUCTION/PURPOSE: Total knee arthroplasty (TKA) in the setting of previous periarticular hardware increases resource utilization, readmissions, complications, and revision rates. Despite the frequency of intramedullary nail (IMN) fixation for tibial fractures, little guidance exists on the management of these patients and no series have reported on outcomes of patients undergoing TKA in the setting of a retained or removed IMN. METHODS: This is a retrospective case series of patients who underwent TKA after IMN fixation of tibial fractures. Patient and case data, including need for hardware removal, staged vs non-staged procedures, operative time, and need for revision implants, were recorded. Postoperative data, including complications and revision, were recorded. Oxford Knee Score (OKS) was performed at follow-up. RESULTS: Nine patients were identified consisting of eight women and one man. Follow-up ranged from 0.8-13 years. Non-staged removal of the intramedullary hardware occurred in three cases that had increased operative lengths recorded. There were no complications related to wound healing or infection. No patients required revision. Two of the three patients who underwent non-staged TKA developed arthrofibrosis requiring manipulation. OKS scores in patients who underwent non-staged surgery were consistently low. CONCLUSIONS: Conversion TKA after tibial IMN fixation can result in satisfying outcomes in many patients. However, intramedullary hardware presents challenges to TKA similar to more extensively studied conversion TKA scenarios. Removing hardware in either a staged or non-staged fashion results in increased resource utilization and imparts perioperative challenges with only theoretical benefits of one approach compared to the other. Increased stiffness may be associated with a non-staged approach to hardware removal and TKA. Several technical factors may permit component positioning without removal of hardware. Despite limitations, this is the first series to discuss this challenging clinical scenario and provides surgeons with technical guidance and data on operative outcomes.

Staged vs Concurrent Hardware Removal During Conversion Total Knee Arthroplasty.

BACKGROUND: Conversion total knee arthroplasty (TKA) in the presence of periarticular hardware can be associated with increased resource utilization, complications, and revisions. However, little guidance exists on the optimal approach to hardware removal. The purpose of this study is to compare outcomes of conversion TKA with hardware removal performed in either a staged or concurrent manner. METHODS: This is a retrospective study of 155 TKA operations performed with staged (45) or concurrent (110) removal of hardware at the time of TKA. Differences in patient data, case data, complications, reoperations, and revisions were evaluated. Subgroup comparisons of cases involving major hardware (plates, nails, rods), minor hardware (screws, buttons, wires), and tibial plates were performed. RESULTS: There were no differences in age, sex, body mass index, or comorbidities between patients who underwent staged or concurrent hardware removal. Rates of complications, reoperations, and revisions did not differ at multiple time points (90 days, 1 year, 2 years, 4 years). Patients who underwent staged hardware removal were more likely to have had prior surgery for fracture reconstruction (68% vs 33%, P < .001), to have had major hardware removed (84% vs 59%, P = .03), and were less likely to have had hardware removal performed through a single incision with TKA (50% vs 92%, P < .001). Subgroup analysis of major and minor hardware cases demonstrated comparable outcomes. CONCLUSION: There remains no established benefit to either a staged or concurrent approach to hardware removal at the time of TKA. This is true regardless of hardware burden. At this time, a case-by-case approach should be taken to conversion TKA in the presence of periarticular hardware.

Outcome of Dual Mobility Constructs for Adverse Local Tissue Reaction Associated Abductor Deficiency in Revision Total Hip Arthroplasty.

BACKGROUND: Treatment of adverse local tissue reaction (ALTR) is challenging owing to high complications and poor outcomes after a revision surgery. As dislocation is the most common cause of reoperation, it is often necessary to use advanced articulations such as dual mobility. This study aims to evaluate the outcome and complication rates after revision surgery with dual mobility constructs, compared to constrained and conventional articulations in the setting of significant abductor deficiency due to ALTR. METHODS: Out of a total of 338 revision total hip arthroplasties for ALTR, 234 patients with a significant tissue necrosis and abductor muscle insufficiency (grade 3) were evaluated. The complication rates after revisions were compared between 42 hips with dual mobility implants, 24 hips with constrained liners, 104 hips with large diameter heads (36-40 mm), and 64 hips with small diameter heads (≤32 mm). RESULTS: After an average of 4 years of follow-up (2.8-8.6), the dual mobility articulation had no dislocation, compared to 4.1% and 15.5% for constrained liner and conventional articulations, respectively (P < .001). Utilization of dual mobility and constrained liner cup also did not increase the risk of nondislocation complications, including periprosthetic joint infection and periprosthetic fracture (P = .18 and .52). CONCLUSIONS: This study demonstrates significantly lower dislocation rates for dual mobility when compared to conventional articulations and comparable to constrained liners in cases of severe abductor deficiency due to ALTR, suggesting that dual mobility implants are viable surgical treatment alternatives to constrained liners to minimize dislocation during revision total hip arthroplasty in the setting of significant abductor deficiency due to ALTR.

S2 Alar Iliac Fixation in Long Segment Constructs, a Two- to Five-Year Follow-up.

STUDY DESIGN: Retrospective review of patients having undergone S2 alar-iliac (S2AI) fixation for long fusions with a minimum two-year follow-up. OBJECTIVES: To report on fusion rates, complications, technique-specific complications of patients having undergone S2AI fixation. SUMMARY OF BACKGROUND DATA: Sacropelvic fixation continues to be a challenge when performing long fusions to the pelvis. S2AI screws have been found to provide solid biomechanical fixation and have been found to have good clinical results in short-term follow-up for pediatric and adult patients. METHODS: Cases were retrospectively reviewed in patients who had placement of S2AI screws for long fusions with at least a two-year follow-up. Demographic data, complications, and reoperations were reviewed. Complications were broken into minor and major categories similar to previous series on pelvic fixation. RESULTS: There were 86 cases identified. Minor and major complications occurred in 29% and 24% of patients, respectively, with the majority of minor complications being intraoperative dural tears. Revision surgery for all causes was performed in 23% of the cohort. Fusion rate at L5-S1 for patients without preoperative pseudarthrosis was 95.3%. Preoperative L5-S1 pseudoarthrosis was identified in 20 patients, 17 (95%) of these went onto fusion after one surgery. There was evidence of S2AI screw lucency in 10.4% of cases. However, the majority of these were asymptomatic. CONCLUSIONS: Sacropelvic fixation using the S2AI technique provides safe, durable fixation with low rates of technique-specific complications and limited need for hardware removal. Complication rates in this series were similar to other series on long fusions to the pelvis. Additionally, fusion rates were high at L5-S1 for both patients with and without preoperative L5-S1 pseudarthrosis. It appears that the S2AI technique is a powerful option for patients with previous L5-S1 pseudarthrosis. LEVEL OF EVIDENCE: Level III.

Comparing hospital outcomes between open and closed tibia fractures treated with intramedullary fixation.

INTRODUCTION: Tibial shaft fractures comprise a large portion of operatively treated long bone fractures, and present with the highest rate of open injuries. Intramedullary fixation has become the standard of care for both open and closed injuries. The rates of short term complications and hospital length of stay for open and closed fractures treated with intramedullary fixation is not fully known. Previous series on tibia fractures were performed at high volume centers, and data were not generalizable, further they did not report on length of stay and the impact of preoperative variables on infections, complications and reoperation. We used a large surgical database to compare these outcomes while adjusting for preoperative risk factors. METHODS: Data were extracted from the ACS-NSQIP database from 2005 to 2014. Cases were identified based on CPT codes for intramedullary fixation and categorized as closed vs open based on ICD9 code. In addition to demographic and case data, primary analysis examined correlation between open and closed fracture status with infection, complications, reoperation and hospital length of stay. Secondary analysis examined preoperative variables including gender, race, age, BMI, and diabetes effect on outcomes. RESULTS: There were 272 cases identified. There were no significant demographic differences between open and closed tibia fracture cases. Open fracture status did not increase the rate of infection, 30day complications, reoperation, or length of stay. The only preoperative factor that correlated with length of stay was age. There was no correlation between BMI, presence of insulin dependent and nondependent diabetes, and any outcome measure. DISCUSSION: When considering the complication rates for open and closed tibial shaft fractures treated with intramedullary fixation, there is no difference between 30-day complication rate, length of stay, or return to the operating room. Our reported postoperative infection rates were comparable to previous series, adding validity to our results. The heterogeneity of the hospitals included in ACS-NSQIP database allow our data to be generalizable. These methods may underrepresent the true occurrence of infection as operatively treated tibia infections may present late, requiring late revision. Despite limitations, the data reflect on the current burden of managing these once devastating injuries.

Acute exercise prevents the development of neuropathic pain and the sprouting of non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury.

Spinal cord injury (SCI) impaired sensory fiber transmission leads to chronic, debilitating neuropathic pain. Sensory afferents are responsive to neurotrophic factors, molecules that are known to promote survival and maintenance of neurons, and regulate sensory neuron transduction of peripheral stimuli. A subset of primary afferent fibers responds only to the glial cell-line derived neurotrophic factor (GDNF) family of ligands (GFLs) and is non-peptidergic. In peripheral nerve injury models, restoration of GDNF or artemin (another GFL) to pre-injury levels within the spinal cord attenuates neuropathic pain. One non-invasive approach to increase the levels of GFLs in the spinal cord is through exercise (Ex), and to date exercise training is the only ameliorative, non-pharmacological treatment for SCI-induced neuropathic pain. The purpose of this study was 3-fold: 1) to determine whether exercise affects the onset of SCI-induced neuropathic pain; 2) to examine the temporal profile of GDNF and artemin in the dorsal root ganglia and spinal cord dorsal horn regions associated with forepaw dermatomes after SCI and Ex; and 3) to characterize GFL-responsive sensory fiber plasticity after SCI and Ex. Adult, female, Sprague-Dawley rats received a moderate, unilateral spinal cord contusion at C5. A subset of rats was exercised (SCI+Ex) on automated running wheels for 20min, 5days/week starting at 5days post-injury (dpi), continuing until 9 or 37dpi. Hargreaves' and von Frey testing was performed preoperatively and weekly post-SCI. Forty-two percent of rats in the unexercised group exhibited tactile allodynia of the forepaws while the other 58% retained normal sensation. The development of SCI-induced neuropathic pain correlated with a marked decrease in the levels of GDNF and artemin in the spinal cord and DRGs. Additionally, a dramatic increase in the density and the distribution throughout the dorsal horn of GFL-responsive afferents was observed in rats with SCI-induced allodynia. Importantly, in SCI rats that received Ex, the incidence of tactile allodynia decreased to 7% (1/17) and there was maintenance of GDNF and artemin at normal levels, with a normal distribution of GFL-responsive fibers. These data suggest that GFLs and/or their downstream effectors may be important modulators of pain fiber plasticity, representing effective targets for anti-allodynic therapeutics. Furthermore, we highlight the potent beneficial effects of acute exercise after SCI.

PHYRN: a robust method for phylogenetic analysis of highly divergent sequences.

Both multiple sequence alignment and phylogenetic analysis are problematic in the "twilight zone" of sequence similarity (≤ 25% amino acid identity). Herein we explore the accuracy of phylogenetic inference at extreme sequence divergence using a variety of simulated data sets. We evaluate four leading multiple sequence alignment (MSA) methods (MAFFT, T-COFFEE, CLUSTAL, and MUSCLE) and six commonly used programs of tree estimation (Distance-based: Neighbor-Joining; Character-based: PhyML, RAxML, GARLI, Maximum Parsimony, and Bayesian) against a novel MSA-independent method (PHYRN) described here. Strikingly, at "midnight zone" genetic distances (~7% pairwise identity and 4.0 gaps per position), PHYRN returns high-resolution phylogenies that outperform traditional approaches. We reason this is due to PHRYN's capability to amplify informative positions, even at the most extreme levels of sequence divergence. We also assess the applicability of the PHYRN algorithm for inferring deep evolutionary relationships in the divergent DANGER protein superfamily, for which PHYRN infers a more robust tree compared to MSA-based approaches. Taken together, these results demonstrate that PHYRN represents a powerful mechanism for mapping uncharted frontiers in highly divergent protein sequence data sets.