Will My Tibial Fracture Heal? Predicting Nonunion at the Time of Definitive Fixation Based on Commonly Available Variables.

BACKGROUND: Accurate prediction of tibial nonunions has eluded researchers. Reliably predicting tibial nonunions at the time of fixation could change management strategies and stimulate further research. QUESTIONS/PURPOSES: We asked (1) whether data from medical records, fracture characteristics, and radiographs obtained at the time of fixation would identify features predictive of tibial fracture nonunion; and (2) whether this information could be used to create a model to assess the chance of nonunion at the time of intramedullary (IM) nail fixation of the tibia. METHODS: We retrospectively reviewed all tibial shaft fractures treated at our center from 2007 to 2014. We conducted a literature review and collected data on 35 factors theorized to contribute to delayed bone healing. Patients were followed to fracture healing or surgery for nonunion. Patients with planned prophylactic nonunion surgery were excluded because their nonunions were anticipated and our focus was on unanticipated nonunions. Our cohort consisted of 382 patients treated with IM nails for tibial shaft fractures (nonunion, 56; healed, 326). Bivariate and multivariate regression techniques and stepwise modeling approaches examined the relationship between variables available at definitive fixation. Factors were included in our model if they were identified as having a modest to large effect size (odds ratio > 2) at the p < 0.05 level. RESULTS: A multiple variable logistic regression model was developed, including seven factors (p < 0.05; odds ratio > 2.0). With these factors, we created the Nonunion Risk Determination (NURD) score. The NURD score assigns 5 points for flaps, 4 points for compartment syndrome, 3 points for chronic condition(s), 2 points for open fractures, 1 point for male gender, and 1 point per grade of American Society of Anesthesiologists Physical Status and percent cortical contact. One point each is subtracted for spiral fractures and for low-energy injuries, which were found to be predictive of union. A NURD score of 0 to 5 had a 2% chance of nonunion; 6 to 8, 22%; 9 to 11, 42%; and > 12, 61%. CONCLUSIONS: The proposed nonunion prediction model (NURDS) seems to have potential to allow clinicians to better determine which patients have a higher risk of nonunion. Future work should be directed at prospectively validating and enhancing this model. LEVEL OF EVIDENCE: Level III, diagnostic study.

Revisiting the polyoxometalate-based late-transition-metal-oxo complexes: the "oxo wall" stands.

Terminal oxo complexes of the late transition metals Pt, Pd, and Au have been reported by us in Science and Journal of the American Chemical Society. Despite thoroughness in characterizing these complexes (multiple independent structural methods and up to 17 analytical methods in one case), we have continued to study these structures. Initial work on these systems was motivated by structural data from X-ray crystallography and neutron diffraction and (17)O and (31)P NMR signatures which all indicated differences from all previously published compounds. With significant new data, we now revisit these studies. New X-ray crystal structures of previously reported complexes K(14)[P(2)W(19)O(69)(OH(2))] and "K(10)Na(3)[Pd(IV)(O)(OH)WO(OH(2))(PW(9)O(34))(2)]" and a closer examination of these structures are provided. Also presented are the (17)O NMR spectrum of an (17)O-enriched sample of [PW(11)O(39)](7-) and a careful combined (31)P NMR-titration study of the previously reported "K(7)H(2)[Au(O)(OH(2))P(2)W(20)O(70)(OH(2))(2)]." These and considerable other data collectively indicate that previously assigned terminal Pt-oxo and Au-oxo complexes are in fact cocrystals of the all-tungsten structural analogues with noble metal cations, while the Pd-oxo complex is a disordered Pd(II)-substituted polyoxometalate. The neutron diffraction data have been re-analyzed, and new refinements are fully consistent with the all-tungsten formulations of the Pt-oxo and Au-oxo polyoxometalate species.

Pseudoaneurysm of the distal thigh after manipulation of a total knee arthroplasty.

The authors describe a unique complication after manipulation of a stiff total knee arthroplasty in a 47-year-old man. Four days after undergoing manipulation under anesthesia (MUA), the patient presented with increasing pain and swelling of the affected knee and decreased hemoglobin/hematocrit. Computed tomographic angiogram revealed a ruptured pseudoaneurysm of a segmental branch of the deep femoral artery that was treated with embolization and anterior thigh compartment fasciotomy. Although many complications of MUA have been described, we present a novel finding of a ruptured pseudoaneurysm. Ruptured pseudoaneurysm should be included in the differential diagnosis whenever a patient presents with pain and swelling of the thigh after MUA given its potential morbidity.

Synthesis and characterization of a metal-to-polyoxometalate charge transfer molecular chromophore.

[P(4)W(35)O(124){Re(CO)(3)}(2)](16-) (1), a Wells-Dawson [α(2)-P(2)W(17)O(61)](10-) polyoxometalate (POM)-supported [Re(CO)(3)](+) complex containing covalent W(VI)-O-Re(I) bonds has been synthesized and characterized by several methods, including X-ray crystallography. This complex shows a high visible absorptivity (ε(470 nm) = 4000 M(-1) cm(-1) in water) due to the formation of a Re(I)-to-POM charge transfer (MPCT) band. The complex was investigated by computational modeling and transient absorption measurements in the visible and mid-IR regions. Optical excitation of the MPCT transition results in instantaneous (<50 fs) electron transfer from the Re(I) center to the POM ligand.

NURD 2.0: Prediction of tibial nonunion after intramedullary nail fixation at any time within 3 months after injury.

Introduction Nonunion after fixation of long bones negatively impacts outcomes and requires additional surgery. The ability to predict likelihood of nonunion after tibial shaft fracture would be helpful to clinicians and patients. The goal of this work was to combine three previous models of tibial shaft nonunion at different time points into one overall model that incorporates time as a continuous variable. Methods We conducted a retrospective review at a Level I academic trauma center. The study cohort consisted of patients with tibial shaft fractures treated with nail insertion from 2007 through 2014, excluding patients who did not have contact between bone ends, those who had planned bone grafting for acute bone defects, and those who lacked adequate follow-up. Three previous models were combined: 382 patients at time 0, 323 at 6 weeks, and 240 at 12 weeks. The primary outcome variable was surgery for nonunion. Bivariate and multivariate regression analyses determined which of 42 clinical and radiographic variables were significantly associated with nonunion. Predictive power was evaluated using area under the curve (AUC). Results The original nonunion risk determination (NURD) score was significantly improved through addition of 6- and 12-week radiographic union scores for tibial fractures, infection and complications, smoking status, and need for flaps. Overall, over the course of 12 weeks, the NURD-based model produced an AUC of 0.87 at initial time of fixation that improved to >0.9 at 6 and 12 weeks. Data were used to bin patients into five clinically important risk strata (p < 0.001). Patients in the lowest risk strata had 0% probability of nonunion (0 of 97 patients); in the second lowest risk strata, 4% (three of 73 patients); and in the highest risk strata, 48% (38 of 80 patients). Conclusions We created a NURD 2.0 score that predicts nonunion at various time points during the first 3 months after fracture. The new model is a notable improvement over previous models. A computerized version allows surgeons and patients to use the score when making treatment decisions regarding need for nonunion surgery.

Predicting tibia shaft nonunions at initial fixation: An external validation of the Nonunion Risk Determination (NURD) score in the SPRINT trial data.

BACKGROUND: Predictive models are common in orthopedic research; however, most models are not validated in an external population. The Nonunion Risk Determination (NURD) score was developed using a single-center cohort of 382 patients to reliably predict tibia shaft nonunions at the time of initial intramedullary nail fixation. The purpose of this study was to externally validate the NURD score using data from the SPRINT Trial. METHODS: The SPRINT trial was a multicenter study comparing reamed versus unreamed intramedullary nails in tibial shaft fracture patients. We assessed the prognostic performance of the NURD score in the SPRINT trial data with comparisons of the c-statistics, calibration plots, and a comparison of predicted probabilities at cut-points defined in the study to derive the NURD score. In addition, we compared the odds ratios of the NURD score components between the derivation (NURD) and external validation (SPRINT) data. RESULTS: The NURD score demonstrated significantly worse discrimination in the SPRINT data than was observed in the original data (c-statistic: 0.61 vs. 0.85, p<0.01). The NURD score was well-calibrated in the derivation and SPRINT data. The SPRINT data had less heterogeneity, as determined by the standard deviation of the linear predictors (NURD: 1.4 vs. SPRINT: 0.4). Once we adjusted for case-mix differences, the NURD score had similarly strong discrimination in the SPRINT data (c-statistic: 0.81 vs. 0.85, p = 0.17). DISCUSSION: Based on our external validation, the NURD score lacks generalizability as it underperforms with respect to discrimination in the SPRINT trial data. However, after adjusting for case-mix differences, the performance of the NURD score is comparable between the two datasets, suggesting robust reproducibility.

Altered bone marrow dendritic cell cytokine production to toll-like receptor and CD40 ligation during chronic feline immunodeficiency virus infection.

Impaired dendritic cell (DC) function is thought to be central to human immunodeficiency virus-associated immunodeficiency. In this study, we examined the effect of chronic feline immunodeficiency virus (FIV) infection on DC cytokine production in response to microbial and T-cell stimulation. Cytokine production after either Toll-like receptor (TLR) or CD40 ligation in bone marrow-derived DCs (BM-DCs) was measured in naïve and chronically FIV-infected cats. The BM-DCs were stimulated with ligands to TLR-2, -3, -4, -7 and -9 or cocultured with 3T3 cells expressing feline CD40 ligand. Ligation of TLR-4 and TLR-9 in BM-DCs from infected cats resulted in a significant decrease in the ratio of interleukin-12 (IL-12) to IL-10. Conversely, TLR-7 ligation produced a significant increase in the IL-12 : IL-10 ratio in BM-DCs from infected cats. No difference was noted for TLR-3 ligation. RNA expression levels of TLR-2, -3, -4, -7 and -9 were not significantly altered by FIV infection. CD40 ligation significantly elevated both IL-10 and IL-12 messenger RNA production but did not alter the IL-12 : IL-10 ratio. Chronic FIV infection alters the ratio of immunoregulatory cytokines produced by BM-DCs in response to certain pathogen-derived signals, which is probably relevant to the increased risk of opportunistic infections seen in lentiviral infection.

Multifunctional multilayer films containing polyoxometalates and bismuth oxide nanoparticles.

Multifunctional multilayer films consisting of the Keggin-type polyoxometalate [SiW(9)V(3)O(40)](7-) (SiW(9)V(3)) and bismuth oxide nanoparticles (Bi(2)O(3)) were prepared by the layer-by-layer assembly method. For the first time, electrochromic and photochromic studies were done on a film containing both polyoxometalates and nanoparticles. The films were characterized by UV-vis absorption, emission spectra, and atomic force microscopy. Their electrochromic and photochromic properties were investigated by cyclic voltammetry and UV-vis spectroscopy. The results show that the reduction of SiW(9)V(3) is very reversible and tunable with the addition of Bi(2)O(3) layers into the film. The electrocatalytic activity of the films toward oxidation of l-cysteine hydrochloride hydrate (l-cysteine) and reduction of nitrite were studied with cyclic voltammetry. The results show that the incorporation of Bi(2)O(3) nanoparticles into the films changed the films' photoluminescence properties and electrocatalytic efficiency.

Development and application of a quantitative real-time PCR assay to detect feline leukemia virus RNA.

We previously defined four categories of feline leukemia virus (FeLV) infection, designated as abortive, regressive, latent, and progressive. To determine if detectable viral DNA is transcriptionally active in the absence of antigenemia, we developed and validated a real-time viral RNA qPCR assay. This assay proved to be highly sensitive, specific, reproducible, and allowed reliable quantitation. We then applied this methodology, together with real-time DNA qPCR and p27 capsid antigen capture ELISA, to examine cats challenged with FeLV. We found that circulating viral RNA and DNA levels were highly correlated and the assays were almost in perfect agreement. This indicates that the vast majority of viral DNA is transcriptionally active, even in the absence of antigenemia. The real-time qPCR assays are more sensitive than the most commonly used FeLV diagnostic assay, the p27 capsid antigen capture ELISA. Application of qPCR assays may add greater depth in understanding of FeLV-host relationships.

Polyoxometalate-encapsulated twenty-nuclear silver-tetrazole nanocage frameworks as highly active electrocatalysts for the hydrogen evolution reaction.

Two unprecedented polyoxometalate-encapsulated twenty-nuclear silver-tetrazole nanocage frameworks have been synthesized, which exhibit high activity in hydrogen evolution reaction. HUST-100 shows an onset overpotential of 148 mV and a Tafel slope of 82 mV dec-1, and the catalytic current density approaches 10 mA cm-2 at an overpotential of 234 mV.

Prediction of tibial nonunion at the 6-week time point.

INTRODUCTION: Intramedullary (IM) nail fixation is a common operative treatment, yet concerns regarding the frequency of complications, such as nonunion, remain. Treatment of tibial shaft fractures remains a challenge, and little evidence of prognostic factors that increase risk of nonunion is available. The aim of this study was to develop a predictive model of tibial shaft fracture nonunion 6 weeks after reamed intramedullary (IM) nail fixation based on commonly collected clinical variables and the radiographic union score for tibial fractures (RUST). METHODS: A retrospective case-control study was conducted. All tibial shaft fractures treated at our level I trauma center from 2007 to 2014 were retrospectively reviewed. Only patients with follow-up until fracture healing or secondary operation for nonunion were included. Fracture gaps ≥3 mm were excluded. A total of 323 patients were included for study. RESULTS: Infection within 6 weeks of operation, standard RUST, and the Nonunion Risk Determination (NURD) score had statistically significant associations with nonunion (odds ratio > or < 1.0; p < 0.01). The NURD score was increasingly predictive of nonunion with decreasing RUST. All patients in the high RUST group (RUST ≥ 10), achieved union regardless of NURD score. In the medium RUST group (RUST 6-9), 25% of patients with a NURD score ≥7 experienced nonunion. In the low RUST group (RUST <6 or infection within 6 weeks), 69% of patients with a NURD score ≥7 experienced nonunion. CONCLUSION: Three variables predicted nonunion. Based on these variables, we created a clinical prediction tool of nonunion that could aid in clinical decision making and discussing prognosis with patients.

An unprecedented 3D POM-MOF based on (7,8)-connected twin Wells-Dawson clusters: synthesis, structure, electrocatalytic and photocatalytic properties.

The first (7,8)-connected polyoxometalate-based metal-organic framework (POM-MOF) has been constructed from seven- and eight-connected twin Wells-Dawson clusters, and possesses the highest connection number of polyoxometalates to any mixed-connected POM-MOF to date and a unique structural motif that contains both organic-inorganic and all-inorganic networks.

Kinetics of early FIV infection in cats exposed via the vaginal versus intravenous route.

To determine the influence of route of virus exposure on early pathogenesis of feline immunodeficiency virus (FIV) infection, cats were exposed to either of two FIV isolates (FIV-B-2542 or FIV-A-PPR) by vaginal or intravenous (IV) inoculation. Exposure to either virus clade by either route of inoculation resulted in vaginal and systemic infection. Peak plasma viremia and tissue proviral burden were 1-3 log(10) greater in cats infected with FIV-B-2542 vs. FIV-A-PPR, irrespective of inoculation route. Plasma RNA levels paralleled provirus titers in FIV-B-2542-infected cats and were highest in those exposed IV. In contrast, plasma RNA titers were higher in cats infected vaginally with FIV-A-PPR than in those infected IV. Despite early differences, PBMC provirus titers were similar in all groups by 9 weeks postinfection. In cats infected IV, but not vaginally, CD4(+) lymphocyte counts declined significantly independent of the magnitude of viremia. Mitogen-induced lymphoproliferation was decreased in all infected cats regardless of CD4(+) cell counts; this decline correlated with the magnitude of peak plasma viremia in FIV-B-2542, but not FIV-A-PPR, infected cats. These results establish that the kinetics of early FIV infection differ with route of exposure as well as virus isolate and that properties extrapolated from one virus isolate may not be universal.

A novel technique for reducing intertrochanteric hip fractures.

Intertrochanteric hip fractures typically become deformed by the muscular and gravitational forces acting on the 2 main bony fragments. Traditional use of a fracture table for anatomical reduction normally corrects for the varus angulation, external rotation, and posterior sag that can occur, but, in select unstable and comminuted fractures, reduction may not be possible because of posterior sag and external rotation of the proximal fragment. These aspects of malreduction have been addressed in multiple ways, including use of unscrubbed assistants, crutches, internal rotation of the distal fragment by internal rotation of the foot, bumps and pads, and even intraoperative techniques. However, these techniques tend to adjust only 1 aspect of malreduction and may require intraoperative adjustment. In this article, we describe a novel surgical device, the pneumatic patient positioner, that can be used to address these deformities without the need for intraoperative adjustment.

Comparative lower limb hemodynamics using neuromuscular electrical stimulation (NMES) versus intermittent pneumatic compression (IPC).

Deep Vein Thrombosis (DVT) is a life threatening condition and a serious concern among hospitalised patients, with death occurring in approximately 6% of cases. Intermittent pneumatic compression (IPC) is commonly used for DVT prevention, however suffers from low compliance and issues of usability and portability. Neuromuscular electrical stimulation (NMES) has been shown to improve lower limb hemodynamics but direct comparison with IPC in terms of hemodynamics is rare but very important to determine the potential effectiveness of NMES in DVT prevention.Lower limb IPC was compared to calf NMES, in 30 healthy volunteers (18-23 years). Each intervention was carried out on each leg, on the popliteal vein measured using Doppler ultrasound. All interventions produced significantly greater haemodynamic responses compared to baseline. Calf-IPC and NMES produced significant increases in venous blood velocity (cm/s) and volume of blood ejected per cycle (1 cycle of NMES expels 23.22 ml compared to the baseline ejected volume of 2.52 ml, measured over 1 s (p < 0.001 versues baseline).Improving lower limb hemodynamics is vital in preventing DVT. NMES resulted in larger ejected volumes compared to IPC (x3 greater than foot-IPC and x1.7 greater than calf-IPC) more effectively emptying the veins and soleal sinuses. This is an important finding as DVT occurs predominantly in the soleal sinuses. NMES is silent and portable and thus does not suffer many of the issues associated with IPC. This work supports the potential widespread application of NMES in hospital and home settings where the risk of DVT formation is high.

The role of accountable care organizations in delivering value.

The goal of Accountable Care Organizations is to improve patient outcomes while maximizing the value of the services provided. This will be achieved through the use of performance and quality measures that facilitate efficient, cost-effective, evidence-based care. By creating a network connecting primary care physicians, specialists, rehabilitation facilities and hospitals, patient care should be maximized while at the same time delivering appropriate value for those services provided. The Medicare Shared Savings Program will financially reward ACOs that meet performance standards while at the same time lowering costs. The orthopaedic surgeon can only benefit by understanding how to participate in and negotiate the complexities of these organizations.

Development and validation of a multiplex microsphere-based assay for detection of domestic cat (Felis catus) cytokines.

Cytokines are essential signaling molecules that mediate the innate immune response, and therefore their presence can be of diagnostic, prognostic, and pathogenic significance. Microsphere-based immunoassays allow rapid and accurate evaluation of cytokine levels in several species, including humans, dogs, and mice; however, technology to evaluate domestic cat (Felis catus) cytokines has been limited to single-analyte enzyme-linked immunosorbent assays (ELISAs). Microsphere-based immunoassays provide an attractive alternative technology for detecting and quantifying multiple analytes in a single assay using as little as 50 µl of sample. We describe the development and validation of a microsphere-based assay for three commonly analyzed domestic cat cytokines (gamma interferon, interleukin-10, and interleukin-12/interleukin-23 p40) using reagents from commercially available ELISAs. The assay was optimized for capture and detection antibody concentrations, streptavidin-phycoerythrin concentration, and number of microspheres. The validated lower and upper quantitation limits were 31 and 1,000 pg/ml for gamma interferon, 63 and 2,000 pg/ml for interleukin-10, and 39 and 625 pg/ml for interleukin-12/interleukin-23 p40. Cytokine concentrations in peripheral blood mononuclear cell supernatants were measured, and results obtained by the microsphere assay were correlated with values obtained with commercially available ELISA kits. This technology is a convenient and reproducible assay to evaluate domestic cat cytokine responses elicited by a variety of diseases.

Utilizing the FIV model to understand dendritic cell dysfunction and the potential role of dendritic cell immunization in HIV infection.

Dendritic cells (DC) are potent antigen presenting cells which initiate and coordinate the immune response making them central targets of and attractive candidates for manipulation in chronic lentiviral infections. Emerging evidence suggests that DC immune function is disrupted during both acute and chronic infection with human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV). Despite some early promising data, the use of DC for lentiviral immunotherapy has not fulfilled its expected potential and has been complicated by the large number of variables involved in DC harvesting, purifying, and antigen loading. Pre-clinical studies aimed at identifying successful strategies for DC augmentation of current HIV treatment protocols are needed. Over the past two decades, the FIV model for HIV infection has increased the understanding of retroviral pathogenesis, and studies have begun using the FIV model to study DC dysfunction and DC-mediated immunotherapy. Careful consideration of the many variables involved in DC function and therapy should help develop protocols to explore the potential of DC vaccine-based therapies for lentiviral infection.

Feline leukemia virus immunity induced by whole inactivated virus vaccination.

A fraction of cats exposed to feline leukemia virus (FeLV) effectively contain virus and resist persistent antigenemia/viremia. Using real-time PCR (qPCR) to quantitate circulating viral DNA levels, previously we detected persistent FeLV DNA in blood cells of non-antigenemic cats considered to have resisted FeLV challenge. In addition, previously we used RNA qPCR to quantitate circulating viral RNA levels and determined that the vast majority of viral DNA is transcriptionally active, even in the absence of antigenemia. A single comparison of all USDA-licensed commercially available FeLV vaccines using these modern sensitive methods has not been reported. To determine whether FeLV vaccination would prevent nucleic acid persistence, we assayed circulating viral DNA, RNA, antigen, infectious virus, and virus neutralizing (VN) antibody in vaccinated and unvaccinated cats challenged with infectious FeLV. We identified challenged vaccinates with undetectable antigenemia and viremia concomitant with persistent FeLV DNA and/or RNA. Moreover, these studies demonstrated that two whole inactivated virus (WIV) adjuvanted FeLV vaccines (Fort Dodge Animal Health's Fel-O-Vax Lv-K) and Schering-Plough Animal Health's FEVAXYN FeLV) provided effective protection against FeLV challenge. In nearly every recipient of these vaccines, neither viral DNA, RNA, antigen, nor infectious virus could be detected in blood after FeLV challenge. Interestingly, this effective viral containment occurred despite a weak to undetectable VN antibody response. The above findings reinforce the precept of FeLV infection as a unique model of effective retroviral immunity elicited by WIV vaccination, and as such holds valuable insights into retroviral immunoprevention and therapy.

Switching slow relaxation in a Mn(III)(3)Mn(IV) cluster: an example of grafting single-molecule magnets onto polyoxometalates.

Binding an established single-molecule magnet cluster of distorted cubane type [Mn(III)(3)Mn(IV)O(4)] to the lacunary site of an {alpha-P(2)W(15)} polyoxotungstate scaffold results in a surprising zero-field splitting inversion and the subsequent loss of magnetization bistability.