Dual T cell receptor/chimeric antigen receptor engineered NK-92 cells targeting the HPV16 E6 oncoprotein and the tumor-associated antigen L1CAM exhibit enhanced cytotoxicity and specificity against tumor cells.

The human papillomavirus type 16 (HPV16) causes a large fraction of genital and oropharyngeal carcinomas. To maintain the transformed state, the tumor cells must continuously synthesize the E6 and E7 viral oncoproteins, which makes them tumor-specific antigens. Indeed, specific T cell responses against them have been well documented and CD8+ T cells engineered to express T cell receptors (TCRs) that recognize epitopes of E6 or E7 have been tested in clinical studies with promising results, yet with limited clinical success. Using CD8+ T cells from peripheral blood of healthy donors, we have identified two novel TCRs reactive to an unexplored E618-26 epitope. These TCRs showed limited standalone cytotoxicity against E618-26-HLA-A*02:01-presenting tumor cells. However, a single-signaling domain chimeric antigen receptor (ssdCAR) targeting L1CAM, a cell adhesion protein frequently overexpressed in HPV16-induced cancer, prompted a synergistic effect that significantly enhanced the cytotoxic capacity of NK-92/CD3/CD8 cells armored with both TCR and ssdCAR when both receptors simultaneously engaged their respective targets, as shown by live microscopy of 2-D and 3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T cell repertoire of healthy donors can be combined with a suitable ssdCAR to enhance the cytotoxic capacity of the effector cells and, indirectly, their specificity.

A costimulatory chimeric antigen receptor targeting TROP2 enhances the cytotoxicity of NK cells expressing a T cell receptor reactive to human papillomavirus type 16 E7.

Immune cells modified to express a tumor-reactive T cell receptor (TCR) have shown limited efficacy as stand-alone therapy against solid tumors. Genital and oropharyngeal carcinomas induced by human papillomavirus (HPV) type 16 express constitutively its E6 and E7 oncoproteins, which makes them convenient targets for adoptive cell immunotherapy. However, viral antigen presentation by tumor cells is low and limits the anti-tumor efficacy of CD8+ T cells. To enhance the functionality of immune effector cells, we have devised a strategy combining a costimulatory chimeric antigen receptor (CAR) with a TCR. We used a clinically tested TCR specific to E7 (E7-TCR) of HPV16 and a newly constructed CAR targeting the trophoblast cell surface antigen 2 (TROP2), which carried the intracellular costimulatory domains CD28 and 4-1BB, but was devoid of the CD3ζ domain. Flow cytometry analyses showed a notable upregulation of activation markers and of cytolytic molecule release by NK-92 cells genetically engineered to express CD3, CD8 and both E7-TCR and TROP2-CAR, after co-incubation with HPV16+ cervical cancer cells. Furthermore, the E7-TCR/TROP2-CAR NK-92 cells demonstrated enhanced antigen-specific activation and augmented cytotoxicity against tumor cells compared with NK-92 cells expressing the E7-TCR alone. A costimulatory TROP2-CAR can synergistically cooperate with the E7-TCR in NK cells thereby enhancing their signaling strength and antigen-specific cytotoxicity. This approach might improve the outcome of adoptive cell immunotherapies for HPV16+ cancer patients that are currently under investigation.

Analysis of the Quality of Prospective Randomized Controlled Trials for Treatment of Boxer's Fractures.

BACKGROUND: This study aimed to review level I and II therapeutic studies on boxer's fractures to measure variation in quality among the highest level study designs. METHODS: We used quantitative measures of study quality to evaluate prospective randomized controlled trials (RCTs) of treatments of boxer's fractures. A search of PubMed, using terms "boxer's fracture" and "fifth metacarpal neck fracture" identified 164 articles from 1961 to 2019. From this list, we identified 6 RCTs. Two observers classified each trial according to 3 systems: the Oxford Levels of Evidence, the modified Coleman Methodology Score, and the revised Consolidated Standards of Reporting Trials (CONSORT) score. RESULTS: The 2 reviewers were consistent in their use of the Oxford Levels of Evidence (100% agreement). The differences between the average modified Coleman Methodology scores and the average CONSORT scores assigned by the 2 observers were not significant (46.2 vs 45.3 points, κ = 0) and (13.7 vs 14.3 points, κ = 0.33), respectively. Both observers rated all the studies as level I and as unsatisfactory according to the Coleman Methodology Score (100% and 100%), and less than half as unsatisfactory according to the CONSORT score (50% and 17%). Areas of deficiency included randomization, blinding, group comparability, clinical effect measurements, and allocation into treatment arms. CONCLUSION: Classifying orthopedic scientific reports according to the levels of evidence implies a degree of respect for level I and II studies that may not always be merited. Our data suggest that the quality of higher level studies, namely those involving boxer's fractures, varies and may often be unsatisfactory when critically evaluated.

Efficiently driving protein-based fragment screening and lead discovery using two-dimensional NMR.

Fragment-based drug discovery (FBDD) and validation of small molecule binders using NMR spectroscopy is an established and widely used method in the early stages of drug discovery. Starting from a library of small compounds, ligand- or protein-observed NMR methods are employed to detect binders, typically weak, that become the starting points for structure-activity relationships (SAR) by NMR. Unlike the more frequently used ligand-observed 1D NMR techniques, protein-observed 2D 1H-15N or 1H-13C heteronuclear correlation (HSQC or HMQC) methods offer insights that include the mechanism of ligand engagement on the target and direct binding affinity measurements in addition to routine screening. We hereby present the development of a set of software tools within the MestReNova (Mnova) package for analyzing 2D NMR for FBDD and hit validation purposes. The package covers three main tasks: (1) unsupervised profiling of raw data to identify outlier data points to exclude in subsequent analyses; (2) batch processing of single-point spectra to identify and rank binders based on chemical shift perturbations or spectral peak intensity changes; and (3) batch processing of multiple titration series to derive binding affinities (KD) by tracing the changes in peak locations or measuring global spectral changes. Toward this end, we implemented and evaluated a set of algorithms for automated peak tracing, spectral binning, and variance analysis by PCA, and a new tool for spectral data intensity comparison using ECHOS. The accuracy and speed of the tools are demonstrated on 2D NMR binding data collected on ligands used in the development of potential inhibitors of the anti-apoptotic MCL-1 protein.

Generation of CAR-T cells using lentiviral vectors.

Cancer immunotherapy is nowadays largely focused on the development of therapeutic antibodies and chimeric antigen receptors (CARs). Two CARs targeting CD19 have been approved recently for the treatment of some hematological malignancies. This demonstrates the capability of engineered CAR T cells in generating effective tumor responses. Furthermore, several hundred ongoing clinical trials are exploring the feasibility of CAR-based approaches to target tumor-associated antigens in solid tumors. However, there still remain significant challenges and limitations in the design and production of CAR-modified T cells that need to be addressed, such as more effective transduction methods, expression and exhaustion issues, reliable in vitro and in vivo characterization methods, etc. Here we describe current techniques for generating CAR T cells using lentiviral vectors as well as detailed protocols for their functional characterization.

Immunogenic T cell epitopes of SARS-CoV-2 are recognized by circulating memory and naïve CD8 T cells of unexposed individuals.

BACKGROUND: Recent studies have provided evidence of T cell reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in significant numbers of non-infected individuals, which has been attributed to cross-reactive CD4 memory T cells from previous exposure to seasonal coronaviruses. Less evidence of cross-reactive memory CD8 T cells has been documented to date. METHODS: We used the NetCTLPan neural network of the Epitope Database and Analysis Resource to select a series of 27 HLA-A*02:01 epitopes derived from the proteome of SARS-CoV-2. Their binding capacity was assessed by a HLA-A*02:01 stabilization assay and by quantifying their binding to HLA-A*02:01 monomers for the generation of tetramers. Their ability to stimulate and induce expansion of SARS-CoV-2 reactive CD8 T cells was measured by flow cytometry. The TCR repertoire of COVID convalescent and healthy unexposed donors was analysed using the MIRA database. FINDINGS: The HLA-A*02:01 epitopes tested were able to stabilise HLA molecules and induce activation of CD8 T cells of healthy unexposed donors. Our results, based on specific tetramer binding, provide evidence supporting the presence of frequent cross-reactive CD8 T cells to SARS-CoV-2 antigens in non-exposed individuals. Interestingly, the reactive cells were distributed into naïve, memory and effector subsets. INTERPRETATION: Our data are consistent with a significant proportion of the reactive CD8 T clones belonging to the public shared repertoire, readily available in absence of previous contact with closely related coronaviruses. Furthermore, we demonstrate the immunogenic capacity of long peptides carrying T cell epitopes, which can serve to isolate virus-specific T cell receptors among the ample repertoire of healthy unexposed subjects and could have application in COVID-19 immunotherapy. Limitations of our study are that it concentrated on one MHC I allele (HLA-A*02:01) and the low numbers of samples and epitopes tested. FUNDING: See the Acknowledgements section.

Perturbation-Based Modeling Unveils the Autophagic Modulation of Chemosensitivity and Immunogenicity in Breast Cancer Cells.

In the absence of new therapeutic strategies, chemotherapeutic drugs are the most widely used strategy against metastatic breast cancer, in spite of eliciting multiple adverse effects and having low responses with an average 5-year patient survival rate. Among the new therapeutic targets that are currently in clinical trials, here, we addressed the association between the regulation of the metabolic process of autophagy and the exposure of damage-associated molecular patterns associated (DAMPs) to immunogenic cell death (ICD), which has not been previously studied. After validating an mCHR-GFP tandem LC3 sensor capacity to report dynamic changes of the autophagic metabolic flux in response to external stimuli and demonstrating that both basal autophagy levels and response to diverse autophagy regulators fluctuate among different cell lines, we explored the interaction between autophagy modulators and chemotherapeutic agents in regards of cytotoxicity and ICD using three different breast cancer cell lines. Since these interactions are very complex and variable throughout different cell lines, we designed a perturbation-based model in which we propose specific modes of action of chemotherapeutic agents on the autophagic flux and the corresponding strategies of modulation to enhance the response to chemotherapy. Our results point towards a promising therapeutic potential of the metabolic regulation of autophagy to overcome chemotherapy resistance by eliciting ICD.

Orthopaedists Versus Radiologists: A Prospective Comparison of Radiographic Interpretation Between Orthopaedists and Radiologists at a Level I Trauma Center.

The purpose of this investigation was to evaluate the difference in response time, accuracy of radiographic interpretation, and frequency of changes in clinical management necessary after inaccurate reads when comparing orthopaedic and radiology providers. Data including provider response time, accuracy of radiographic interpretation and the frequency of changes in clinical management necessary after imaging reads was collected over a continuous two-month period at a Level I Trauma center. A total of 188 orthopedic injuries involving imaging were included. Orthopedic providers responded 203.2 minutes sooner than radiology providers. Accuracy of radiographic interpretation of the orthopaedic and radiology providers was 100% and 91%, respectively. Frequency of changes in clinical management after inaccurate interpretation of imaging by the orthopaedic and radiology provider was 0% and 7.6%, respectively. Based on our study, orthopaedic providers are significantly faster, more accurate, and make fewer mistakes affecting patient care while interpreting images of orthopaedic injuries than our radiology colleagues. (Journal of Surgical Orthopaedic Advances 30(2):093-096, 2021).

A Tri-Band Cooled Receiver for Geodetic VLBI.

This paper shows a simultaneous tri-band (S: 2.2-2.7 GHz, X: 7.5-9 GHz and Ka: 28-33 GHz) low-noise cryogenic receiver for geodetic Very Long Baseline Interferometry (geo-VLBI) which has been developed at Yebes Observatory laboratories in Spain. A special feature is that the whole receiver front-end is fully coolable down to cryogenic temperatures to minimize receiver noise. It was installed in the first radio telescope of the Red Atlántica de Estaciones Geodinámicas y Espaciales (RAEGE) project, which is located in Yebes Observatory, in the frame of the VLBI Global Observing System (VGOS). After this, the receiver was borrowed by the Norwegian Mapping Autorithy (NMA) for the commissioning of two VGOS radiotelescopes in Svalbard (Norway). A second identical receiver was built for the Ishioka VGOS station of the Geospatial Information Authority (GSI) of Japan, and a third one for the second RAEGE VGOS station, located in Santa María (Açores Archipelago, Portugal). The average receiver noise temperatures are 21, 23, and 25 Kelvin and the measured antenna efficiencies are 70%, 75%, and 60% in S-band, X-band, and Ka-band, respectively.

Functional outcomes of patients with stroke treated with thrombectomy by aspiration.

Purpose: To determine the time of procedure, the value of modified Thrombolysis in Cerebral Infarction and National Institute Health of Stroke Scale as predictors of the functional results of patients with stroke treated with mechanical thrombectomy by aspiration.Methods: Observational, analytical, and retrospective case series analysis of consecutive patients with internal carotid and cerebral media branch occlusions. Clinical outcome was measured with the modified Rankin Scale at 90 days after stroke. To analyze the differences between groups, the Chi2 test was used for the qualitative variables.Results: The sample size was 58 patients treated with thrombectomy by aspiration. We observed that the thrombectomy time determines the recanalization results; meanwhile, modified Thrombolysis in Cerebral Infarction is a predictor of modified Rankin Scale at discharge but not after 3 months. National Institute Health of Stroke Scale was determinant for modified Rankin Scale result.Conclusions: Mechanical thrombectomy by aspiration proves to be an effective treatment of acute stroke, improving the patient's vital and functional prognosis. The thrombectomy time is a predictor of the result in relation to the degree of recanalization determined by the modified Thrombolysis in Cerebral Ischemia. Also, the degree of recanalization predicts functional outcome at discharge but not at 3 months.

Supercharge End-to-Side Nerve Transfer: Systematic Review.

Background: To decrease the time to reinnervation of the intrinsic motor end plates after high ulnar nerve injuries, a supercharged end-to-side (SETS) anterior interosseous to ulnar motor nerve transfer has been proposed. The purpose of this study was to compile and review the indications, outcomes, and complications of SETS anterior interosseous to ulnar motor nerve transfer. Methods: A literature search was performed, identifying 73 papers; 4 of which met inclusion and exclusion criteria, including 78 patients. Papers included were those that contained the results of SETS between the years 2000 and 2018. Data were pooled and analyzed focusing on the primary outcomes: intrinsic muscle recovery and complications. Results: Four studies with 78 patients met inclusion and exclusion criteria. Most patients (33.3%) underwent SETS for an ulnar nerve lesion in continuity, the average age was 46.5 years, and the average follow-up was 10 months. The average duration of symptoms before surgery was 99 weeks, all patients had weakness and numbness, nearly all (96%) had atrophy, and half (53%) had pain. Grip and key pinch strength improved 202% and 179%, respectively, from the preoperative assessment. The vast majority (91.9%) recovered intrinsic function at an average of 3.7 months. Other than 8% of patients who did not recover intrinsic strength, no other complications were reported in any of the 78 patients. Conclusions: The SETS is a successful procedure with low morbidity, which may restore intrinsic function in patients with proximal nerve injuries.

Walking Greater Than 5 Feet After Hip Fracture Surgery Is Associated With Fewer Complications, Including Death.

INTRODUCTION: Hip fractures in the elderly are associated with notable morbidity. The influence of postoperative ambulation on outcomes is not well described. We hypothesized that patients who mobilize faster after surgical intervention would demonstrate fewer postoperative complications. METHODS: A retrospective review was performed on patients with hip fractures from October 2015 through September 2017. All ambulatory patients at least 65 years old (y/o), with a low-energy mechanism of injury, and who underwent surgical treatment were included. Physical therapy notes were used to track postoperative ambulation, and medical records were reviewed for 90-day postoperative complications. RESULTS: One hundred sixty-three patients were included (64 femoral neck, 88 intertrochanteric, and 11 subtrochanteric fractures). Eighty patients had postoperative complication(s). Walking >5 feet by 72 hours postoperatively was associated with decreased morbidity (complication rate: 31% versus 77% (≤5 feet ambulation), P < 0.001). Walking >5 feet by 72 hours postoperatively decreased the likelihood of myocardial infarction (P = 0.003), pneumonia (P = 0.021), intensive care unit admission (P < 0.001), and death or hospice transfer (P < 0.001). DISCUSSION: Ambulating >5 feet within 72 hours postoperatively is associated with a lower postoperative complication rate. To our knowledge, this study is the first to quantify the relationship between postoperative hip fracture mobilization and morbidity and mortality. LEVEL OF EVIDENCE: Prognostic, Level III.

Frecuencias de grupos sanguíneos de interés clínico en donantes y pacientes de Costa Rica / The frequency of blood groups of interest in donors and patients from Costa Rica

Introducción: Los sistemas sanguíneos ABO, Rh y Kell son lo más relevantes desde el punto de vista clínico por su inmunogenicidad y ser los principales causantes de reacciones hemolíticas. Objetivo: Determinar las frecuencias de los grupos sanguíneos ABO y Rh, y la frecuencia del antígeno Kell en pacientes y donantes de Costa Rica. Métodos: Durante el periodo de 2009 al 2018 se obtuvo de las bases de datos de los bancos de sangre de tres hospitales de adultos de Costa Rica, las frecuencias de los grupos sanguíneos ABO, Rh y Kell en muestras de donantes y pacientes. Para contrastar las frecuencias de cada grupo sanguíneo se realizó una prueba de independencia de variables Chi cuadrado, con el 95 por ciento de confianza. Los datos se analizaron con el paquete estadístico SPSS versión 23. Resultados: Las frecuencias de los grupos ABO en las muestras de donantes y pacientes mostraron diferencias pequeñas pero significativas. La frecuencia del fenotipo Rh D negativo fue más alta en pacientes (8,0 por ciento) que en donantes (6,1 por ciento). Se estimaron las frecuencias de los antígenos C (67,8 por ciento), c (80,5 por ciento), E (41,4 por ciento), e (94,4 por ciento) y K (3,1 por ciento) a partir de las muestras de los donantes. Conclusiones: Las estrategias de reclutamiento de donantes de sangre aumentan la frecuencia del fenotipo Rh negativo en donantes con respecto a los pacientes. Las estadísticas recopiladas demuestran un aumento en la frecuencia del grupo O en comparación con los últimos estudios relacionados. Finalmente, los otros antígenos presentaron pocas variaciones en comparación a estudios previos(AU)

Introduction: The ABO, Rh and Kell blood systems are the most relevant from the clinical point of view, due to their immunogenicity and because they are the main causes of hemolytic reactions. Objective: To determine the frequencies of ABO and Rh blood groups, and the frequency of the Kell antigen in patients and donors from Costa Rica. Methods: During the period from 2009 to 2018, the frequencies of ABO, Rh and Kell blood groups in donor and patient samples were obtained from the blood bank databases of three adult hospitals in Costa Rica. To contrast the frequencies of each blood group, a chi-square test of independence of variables was performed, with 95 percent confidence interval. The data were analyzed with the statistical package SPSS version 23. Results: The frequencies of ABO groups in donor and patient samples showed small but significant differences. The frequency of the negative Rh D phenotype was higher in patients (8.0 percent) than in donors (6.1 percent). The frequencies of the antigens C (67.8 percent), c (80.5 percent), E (41.4 percent), e (94.4 percent), and K (3.1 percent) were estimated from donor samples. Conclusions: Blood donor recruitment strategies increase the frequency of negative Rh phenotype in donors compared to patients. The statistics collected demonstrate an increase in the frequency of the O group compared to recent related studies. Finally, the other antigens did not show as much variation compared to previous studies(AU)

Impact of the Fascia Iliaca Block on Pain, Opioid Consumption, and Ambulation for Patients With Hip Fractures: A Prospective, Randomized Study.

OBJECTIVES: To determine the effect of the fascia iliaca block (FIB) on patients undergoing surgery for hip fractures. DESIGN: Prospective, randomized controlled trial. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Patients (N = 97) undergoing surgery for hip fractures were prospectively randomized to receive either a perioperative FIB (FIB group) or no block (control group) from February 2018 to April 2019. MAIN OUTCOME MEASURES: Visual analog scale (VAS) score, morphine milligram equivalents, and postoperative ambulatory distance. RESULTS: Fifty-seven patients were randomized to the FIB group, and 40 patients were randomized to the control group. Eighteen patients crossed over from the FIB to the control group, and 12 patients crossed over from the control to the FIB group. In the intent-to-treat analysis, demographic data, mechanism of injury, radiographic fracture classification, and surgical procedure were similar between the 2 groups. The FIB group consumed fewer morphine milligram equivalents before surgery (13 vs. 17, P = 0.04), had a trend toward an improved visual analog scale score on postoperative day 2 (0 vs. 2 P = 0.06), and walked a farther distance on postoperative day 2 (25' vs. 2', P = 0.09). A greater proportion of the FIB group were discharged home (50.9% vs. 32.5%, P = 0.05). There were no differences in opioid-related, block-related, or medical complications between groups. In the as-treated and per-protocol analyses, there were no significant differences. CONCLUSIONS: A single perioperative FIB for patients with hip fractures undergoing surgery may decrease opioid consumption and increase the likelihood that a patient is discharged home. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Alleviation of Pain After Femur and Tibia Shaft Fractures Using Nothing Stronger Than Codeine and Tramadol.

OBJECTIVE: To determine whether using nothing stronger than codeine and tramadol provides adequate pain alleviation in people recovering from fixation of a fracture of the femur or tibia shaft. DESIGN: Retrospective case series. SETTING: Level 1 trauma center in the United States. PATIENTS: All adult patients from October 2016 to October 2018 with femur (OTA/AO 32) and tibial (OTA/AO 42) shaft fractures who were treated surgically were included. A nurse counseled patients on safe and effective alleviation of pain. Charts were reviewed for pain medication prescribed, noting utilization of schedule II opioid medications. MAIN OUTCOME MEASURES: Frequency of schedule II pain medication prescription on discharge or during follow-up, emergency department presentation for pain, or readmission for pain. RESULTS: One hundred fifty patients with 162 fractures were treated for femoral (N = 73 fractures) or tibial (N = 89 fractures) shaft fractures. Sixty patients (40%) were multiple injured patients. Thirteen (8.7%) patients were discharged with hydrocodone, oxycodone, or fentanyl. Of the remaining patients with adequate follow-up (N = 109), 6.4% requested hydrocodone, oxycodone, or fentanyl after discharge. There was 1 patient presentation to the emergency department for pain, and there were no pain-related readmissions. CONCLUSIONS: Alleviation of pain can be achieved in most patients with femoral and tibial shaft fractures, including multiply injured patients, with one-on-one patient support and by using nothing stronger than codeine and tramadol. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Outcomes and Return to Work Following Complex Nerve Lacerations in the Volar Forearm in an Underserved Spanish-Speaking Population.

Purpose: Lacerations to the ulnar and median nerve in the volar forearm have demonstrated considerable long-term clinical and socioeconomic impacts on patients. The purpose of this study was to evaluate the outcomes of complex volar forearm lacerations involving one or more major peripheral nerves in an economically disadvantaged patient population. Methods: In this study, a retrospective analysis of 61 patients who sustained lacerations to the median nerve, ulnar nerve, or both with volar wrist lacerations was performed. Each patient's preinjury and postinjury occupation, dominant extremity, and demographic variables were evaluated. Sensation recovery, motor recovery, Disabilities of the Arm, Shoulder, and Hand scores, visual analog scale scores, cold intolerance, and return to work were evaluated at 3, 6, and 12 months after the injury. Results: Patients with isolated median nerve injuries demonstrated improved motor recovery compared with patients with isolated ulnar nerve injuries. Patients with combined nerve injuries had worse sensation recovery and motor recovery, and lower rates of return to work than either group of patients with isolated nerve injuries. Manual laborers had worse motor recovery and lower rates of return to work than did patients who were office workers. Conclusions: Patients with combined median and ulnar nerve injuries have worse functional recovery and lower rates of return to work than do patients with isolated median or isolated ulnar nerve injuries at 1 year. Manual laborers demonstrated worse functional recovery and lower rates of return to work compared with office workers at 1 year. Type of study/level of evidence: Therapeutic III.

Abstracts Accepted for Presentation at Orthopaedic Trauma or Arthroplasty Conferences: Which Conference Is the Best Indicator of Future Publication?

Time and financial resources pose limitations to orthopaedic surgeons wishing to advance their orthopaedic knowledge, and surgeons frequently must choose one meeting to attend. We sought to determine whether abstracts presented at the American Academy of Orthopaedic Surgeons (AAOS) annual meeting or the trauma (Orthopaedic Trauma Association [OTA]) or arthroplasty (American Association of Hip and Knee Surgeons [AAHKS]) subspecialty meetings, respectively, were higher yield with respect to material ultimately being published. We hypothesized that papers accepted by AAOS would demonstrate higher conversion to publication compared with OTA and AAHKS but expected abstract publication rates from OTA and AAHKS to be similar. METHODS: All clinical and preclinical abstracts from the trauma and total joint arthroplasty subspecialties presented at the AAOS, OTA, and AAHKS annual meetings in 2015 were evaluated. Data collected included the current status of the publication, journal and publication date, time to publication, and country of origin (United States or international). RESULTS: There were 516 (N = 213, AAOS; N = 303, OTA) trauma and 711 (N = 470, AAOS; N = 241 AAHKS) arthroplasty poster and podium presentations. When comparing publication rates in trauma, no significant difference was observed in overall publication rates between AAOS and OTA at 57.2% (N = 122 published) and 60.4% (N = 183 published), respectively (P = 0.54). In addition, no significant difference was observed in overall publication rates in arthroplasty between AAOS and AAHKS, with publication rates of 65.3% (N = 307 published) and 59.8% (N = 144 published), respectively (P = 0.17). Of abstracts that were published, AAHKS arthroplasty abstracts were more likely to be published in The Journal of Arthroplasty (JOA, 69.4%) compared with OTA trauma abstracts published in the Journal of Orthopaedic Trauma (JOT, 33.3%), P < 0.001. CONCLUSION: The overall publication rates, along with publication rates to premiere subspecialty journals, is indicative of forefront research being presented at the three annual meetings. Given the comparable research quality of OTA and AAHKS abstracts, the AAOS meeting appears to provide the highest yield for surgeons with more generalized practices or practices spanning multiple subspecialties.

Diabetic Control Predicts Surgical Site Infection Risk in Orthopaedic Trauma Patients.

OBJECTIVES: (1) To determine the incidence of surgical site infections (SSIs) in diabetic orthopaedic trauma patients and (2) to establish a protocol for managing diabetes mellitus (DM) in orthopaedic trauma patients. DESIGN: Retrospective cohort study. SETTING: Level 1 Trauma Center. PATIENTS: All diabetic orthopaedic trauma patients who underwent surgical intervention with at least 1 month follow-up. Patients were classified as poorly controlled or controlled diabetic patients based on admission hemoglobin A1c and blood glucose (BG) levels. INTERVENTIONS: Orthopaedic surgical intervention in accordance with fracture type and a standardized diabetes management protocol with internal medicine comanagement. MAIN OUTCOME MEASUREMENT: SSI incidence. RESULTS: There were 260 patients during the study period. Two hundred two (77.7%) were included in the final analysis. Seventy-five (37.1%) patients met the criteria for poorly controlled DM. The overall rate of SSI was 20.8%; 32.0% for poorly controlled diabetic patients, and 14.2% for controlled diabetic patients (P < 0.01). The admission blood glucose level (BG, P = 0.05), but not discharge BG, was associated with SSI incidence. CONCLUSIONS: Trauma patients with poorly controlled DM have a higher rate of SSIs than patients with controlled DM. Perioperative diabetes control does not seem to decrease infection rates in these patients. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Evaluation of the Area of the Lisfranc Ligament Damaged by Screw Fixation.

BACKGROUND: A cannulated screw is currently the standard fixation method to reduce and stabilize diastasis at the lisfranc joint following injury. Currently, there is no literature examining the area of the lisfranc ligament damaged by screw placement. The objective of this investigation is to define the area of the ligament damaged by fixation with a 3.5-mm cannulated screw. MATERIALS AND METHODS: Twelve cadaveric feet were dissected to identify the Lisfranc ligament metatarsal insertion site and origin on the medial cuneiform. A 3.5-mm cannulated screw was then passed over the course of the ligament and removed. The Lisfranc joint was then dissected to measure the dimensions of the ligament and damage from screw passage at the origin and insertion using imaging software. RESULTS: Mean injury area on the metatarsal was 3.49 mm2 and the area of injury for the cuneiform was 3.33 mm2. The mean percent of the area damaged was calculated to be 1.75% and 2.43% at the cuneiform and metatarsal, respectively. CONCLUSION: A proportionally small area of the Lisfranc ligament is disrupted following screw fixation, but the implications of this on ligament healing and outcomes remain to be elucidated. LEVELS OF EVIDENCE: Level V: Cadaveric study.

Adding deltoid ligament repair in ankle fracture treatment: Is it necessary? A systematic review.

BACKGROUND: Deltoid ligament injuries are typically caused by supination-external rotation or pronation injury. Numerous ligament reconstruction techniques have been proposed; however, clear indications for operative repair have not yet been well established in the literature. METHODS: We reviewed primary research articles comparing ORIF treatment for ankle fracture with versus without deltoid ligament repair. RESULTS: Five studies were identified with a total of 281 patients. 137 patients underwent ORIF with deltoid repair, while 144 patients underwent ORIF without deltoid ligament repair. Clinical, radiographic, and functional outcomes, as well as complications were considered. The average follow-up was 31 months (range, 5-120). CONCLUSIONS: Current literature does not provide clear indication for repair of the deltoid ligament at the time of ankle fracture repair. There may be some advantages of adding deltoid ligament repair for patients with high fibular fractures or in patients with concomitant syndesmotic fixation. LEVEL OF CLINICAL EVIDENCE: III.