Open Fixation After Preperitoneal Pelvic Packing Is Associated With a High Surgical Site Infection Rate.

OBJECTIVES: To evaluate the incidence of pelvic space surgical site infection (SSI) after preperitoneal pelvic packing (PPP) for persistent hemodynamic instability. DESIGN: Retrospective comparative study. SETTING: Urban Level 1 trauma center. PATIENTS/PARTICIPANTS: 83 patients who received PPP and 55 patients who had open reduction and internal fixation (ORIF) of the anterior pelvic ring without PPP. INTERVENTION: Operative fixation. MAIN OUTCOME MEASUREMENTS: Pelvic space SSI. RESULTS: The SSI rate in the PPP group was 31.3% (26/83) compared with 10.9% (6/55) in the control group (proportional difference 20.4%, confidence interval (CI) 6.4-32.5, P = 0.007). Patients in the PPP group (n = 43) were 1:1 propensity score matched with patients in the control group to account for differences in Injury Severity Score and American Society of Anesthesiologists score. In this matched cohort, the rate of pelvic space SSI remained higher in the PPP group compared with that in the control group (30.2% vs. 9.3%; proportional difference 20.9%, CI, 3.7-36.3; P = 0.02). On multivariate analysis of the PPP group, anterior ORIF (odds ratio 6.56, CI, 2.00-21.47, P = 0.002) was found to be independently associated with SSI. CONCLUSIONS: PPP is an independent risk factor of space SSI. The likelihood of SSI after PPP is increased with anterior ORIF. The morbidity of SSI after PPP must be weighed against the risk of exsanguination. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Nonoperative management of minimally displaced lateral compression type 1 (LC1) injuries with comminuted rami fractures is associated with late displacement.

PURPOSE: Rami comminution has been found to be predictive of lateral compression type 1 (LC1) injury instability on examination under anesthesia (EUA) and lateral stress radiographs (LSR). The purpose of this study was to evaluate how rami comminution and subsequent operative vs. nonoperative management impact the late displacement of these injuries. METHODS: Retrospective review of a prospectively collected LC1 database was performed to identify all patients with minimally displaced LC1 injuries (< 1 cm) and follow-up radiographs over a four-year period (n = 125). Groups were separated based on the presence of rami comminution and subsequent management, including rami comminution/operative (n = 49), rami comminution/nonoperative (n = 54), and no comminution/nonoperative (control group, n = 22). The primary outcome was late fracture displacement, analyzed as both a continuous variable and as late displacement ≥ 5 mm. RESULTS: As a continuous variable, late fracture displacement was lower in the comminuted rami/operative group as compared to the comminuted rami/nonoperative group (PD: -3.0 mm, CI: -4.8 to -1.6 mm, p = 0.0002) and statistically non-different from control. Late displacement ≥ 5 mm was significantly more prevalent in the comminuted rami/nonoperative group than in the comminuted rami/operative and no comminution/nonoperative groups (control)(PD: -33.9%, CI: -49.0% to -16.1%, p = 0.0002 and PD: -30.0%, CI: -48.2% to -6.5%, p = 0.02, respectively). CONCLUSION: Late fracture displacement was greatest in the group with rami comminution/nonoperative management. Rami comminution, which has been previously associated with dynamic displacement on EUA and LSR, is also associated with a higher incidence of late displacement when managed nonoperatively. LEVEL OF EVIDENCE: Level III, prognostic retrospective cohort study.

Percutaneous pelvic fixation model: an affordable and realistic simulator for pelvic trauma training.

PURPOSE: To describe the construction and use of a percutaneous pelvic fixation model, evaluate its translational validity among fellowship-trained orthopedic trauma surgeons, and investigate the importance of specific criteria for effective competency-based assessment of pelvic fixation techniques. METHODS: Five orthopedic trauma surgeons were asked to place percutaneous wires on a pelvic fixation model, including anterior column (antegrade/retrograde), posterior column (antegrade/retrograde), supra-acetabular, transsacral, and iliosacral. Evaluation criteria included successful wire placement, redirections, cortical breaches, procedure duration, radiation exposure, and quality of fluoroscopic views. Following completion, participants were provided a survey to rate the model. RESULTS: There were no differences between approaches on successful screw placement, wire redirections, or fluoroscopic quality. Antegrade approaches to the anterior and posterior columns took longer (p = 0.008) and used more radiation (p = 0.02). There was also a trend toward more cortical breaches with the antegrade anterior column approach (p = 0.07). Median ratings among surgeons were 4 out of 5 for their overall impression and its accuracy in tactile response, positioning constraints, and fluoroscopic projections. Learning parameters considered most important to the progression of trainees (most to least important) were successful screw placement, corridor breaches, wire redirections, quality of fluoroscopic views, radiation exposure, and procedure duration. CONCLUSION: In being affordable, accessible, and realistic, this percutaneous pelvic fixation model represents an opportunity to advance orthopedic surgery education globally. Future research is needed to validate the findings of this pilot study and to expand upon how trainees should be evaluated within simulations and the operating room to optimize skill progression.

Acute Fixation Protocol for High-Energy Tibial Pilon Fractures Decreases Time to Fixation and Lowers Operative Costs Without Affecting Wound Complications and Reoperations.

OBJECTIVES: To determine whether an acute fixation protocol for high-energy tibial pilon fractures increases the rate of wound complications. DESIGN: Retrospective comparative study. SETTING: Urban level 1 trauma center. PATIENTS/PARTICIPANTS: One hundred forty-seven patients with OTA/AO 43B and 43C high-energy tibial pilon fractures treated with open reduction and internal fixation (ORIF). INTERVENTION: Acute (<48 hours) versus delayed ORIF protocols. MAIN OUTCOME MEASUREMENT: Wound complications, reoperations, time to fixation, operative costs, and hospital length of stay (LOS). Patients were compared by protocol, regardless of ORIF timing, for an intention-to-treat analysis. RESULTS: Thirty-five and 112 high-energy pilon fractures were treated under the acute and delayed ORIF protocols, respectively. In the acute ORIF protocol group, 82.9% of patients received acute ORIF versus 15.2% of patients in the standard delayed protocol group. The 2 groups had no observed difference (OD) in the rate of wound complications (OD -5.7%, confidence interval (95% CI) -16.1% to 7.8%; P = 0.56) or reoperations (OD -3.9%, 95% CI, -14.1% to 9.4%; P = 0.76). The acute ORIF protocol group had a shorter LOS (OD -2.0, 95% CI, -4.0 to 0.0; P = 0.02) and lower operative costs (OD $-2709.27, 95% CI, -3582.02 to -1601.16; P < 0.01). On multivariate analysis, wound complications were associated with open fractures (odds ratio 3.36, 95% CI, 1.06-10.69; P = 0.04) and an American Society of Anesthesiologists score >2 (odds ratio 3.68, 95% CI, 1.07-12.67; P = 0.04). CONCLUSION: This study suggests that an acute fixation protocol for high-energy pilon fractures decreases time to definitive fixation, lowers operative costs, and shortens hospital LOS without affecting wound complications or reoperations. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Early Outcomes of Operative Versus Nonoperative Management of Stress-Positive Minimally Displaced Lateral Compression Type 1 Pelvic Ring Injuries.

OBJECTIVES: To compare the early outcomes of patients with stress-positive minimally displaced lateral compression type 1 (LC1b) pelvic ring injuries managed with or without operative fixation. DESIGN: Retrospective comparison study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Forty-three patients with LC1b injuries. INTERVENTION: Operative versus nonoperative. MAIN OUTCOME MEASUREMENTS: Discharge to subacute rehabilitation (SAR); 2- and 6-week pain visual analog score, opioid use, assistive device use, percentage of normal single assessment numerical evaluation, SAR status; fracture displacement; and complications. RESULTS: The operative group did not differ in age, gender, body mass index, high-energy mechanism, dynamic displacement stress radiographs, complete sacral fractures, Denis sacral fracture classification, Nakatani rami fracture classification, follow-up length, or American Society of Anesthesiologists classification. The operative group was less likely to be using an assistive device at 6 weeks [observed difference (OD) -53.9%, 95% confidence interval (CI) -74.3% to -20.6%, OD/CI 1.00, P = 0.0005], less likely to remain in an SAR at 2 weeks (OD -27.5%, CI, -50.0% to -2.7%, OD/CI 0.58, P = 0.02), and had less fracture displacement at follow-up radiographs (OD -5.0 mm, CI, -9.2 to -1.0 mm, OD/CI 0.61, P = 0.02). There were no other differences in outcomes between treatment groups. Complications occurred in 29.6% (n = 8/27) of the operative group compared with 25.0% (n = 4/16) of the nonoperative group resulting in 7 and 1 additional procedures, respectively. CONCLUSIONS: Operative treatment was associated with early benefits over nonoperative management, including shorter time using assistive devices, less SAR use, and less fracture displacement at follow-up. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Operative Management of Stress-Positive Minimally Displaced Lateral Compression Type 1 (LC1) Pelvic Ring Injuries: Analysis of Outcomes Before and After Implementation of a Departmental Stress Protocol.

OBJECTIVES: To compare the hospital course of patients with minimally displaced (<1 cm) lateral compression type 1 injuries treated before and after implementation of lateral stress radiographs (LSRs) to determine management. DESIGN: Retrospective comparative cohort. SETTING: Urban level 1 trauma center. PATIENTS/PARTICIPANTS: Isolated lateral compression type 1 injuries managed before (n = 33) and after implementation of LSRs (n = 40) to determine management. INTERVENTION: Patients in a prestress cohort managed nonoperatively versus patients in an LSR cohort managed operatively if stress positive (≥1 cm displacement on LSRs). MAIN OUTCOME MEASUREMENTS: Physical therapy clearance before discharge, discharge location, hospital length of stay, and inpatient opioid morphine milligram equivalents were measured. RESULTS: The prestress and LSR protocol groups were similar in demographic/injury characteristics (age, sex, mechanism, American Society of Anesthesiologists score, Nakatani classification, bilateral/unilateral injury, Denis zone, sacral fracture completeness, and sacral comminution). Forty-five percent of LSR protocol patients were stress-positive (n = 18) and managed operatively. The LSR protocol group was more likely to clear physical therapy by discharge (97.5% vs. 75.8%, PD: 21.7%, 95% CI: 5.1%-36.8%, P = 0.009), less likely to discharge to a rehabilitation facility (2.5% vs. 18.2%, PD: -15.7%, CI: -30.0% to -0.5%, P = 0.04), and had no difference in length of stay (MD: 0.0, CI:-1.0 to 1.0, P = 0.57) or inpatient opioid morphine milligram equivalents (MD: 9.0, CI: -60.0 to 101.0, P = 0.71). CONCLUSION: Implementation of an LSR protocol to determine management of minimally displaced stress-positive lateral compression type 1 injuries was associated with increased rates of operative management, physical therapy clearance by discharge, and a reduction in the number of patients discharging to rehabilitation facilities. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Geriatric Patients Presenting With Isolated Pubic Rami Fractures and Inability to Mobilize May Have Occult Lateral Compression Pelvic Ring Injuries With Dynamic Instability.

OBJECTIVES: To determine the incidence of patients with isolated pubic rami fractures on computed tomography scans who have dynamic instability secondary to occult lateral compression pelvic ring injuries. DESIGN: Retrospective comparison study. SETTING: Urban level 1 trauma center. PATIENTS/PARTICIPANTS: This study included geriatric patients with isolated pubic rami fractures and inability to mobilize secondary to pain. INTERVENTION: Lateral stress radiographs of pelvis to evaluate for ≥1 cm dynamic instability. MAIN OUTCOME MEASUREMENTS: Physical therapy clearance, hospital length of stay, and discharge location. RESULTS: A total of 19 patients were identified over 12 months. Patients were predominantly geriatric (median age: 75 years, interquartile range: 67 to 90), woman (11/19), with unilateral (17/19) comminuted distal rami fractures (12/19) sustained in ground-level falls (12/19). Dynamic instability was identified in 42% of patients (8/19). Magnetic resonance imaging, obtained in 6 of these patients, demonstrated occult posterior ring fractures in all cases. Patients with dynamic instability were more likely to have comminuted distal rami fractures (Nakatani type 1b) and a longer hospital length of stay. There was also a trend for these patients to be unable to clear physical therapy by discharge (63% (5/8) versus 36% (4/11)). The 90-day mortality rate of the cohort was 16% (3/19). CONCLUSIONS: Patients presenting with seemingly isolated pubic rami fractures on radiographs and computed tomography scans who are unable to mobilize may have occult lateral compression injuries with dynamic instability. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Combined Anterior-Posterior versus Posterior-Only Fixation of Stress-Positive Minimally Displaced Lateral Compression Type 1 (LC1) Pelvic Ring Injuries.

OBJECTIVES: To compare hospital outcomes and late displacement between stress-positive minimally displaced lateral compression type 1 (LC1) pelvic ring injuries treated with combined anterior-posterior versus posterior-only fixation. DESIGN: Retrospective comparative cohort. SETTING: Urban level-one trauma center. PATIENTS/PARTICIPANTS: LC1 injuries managed operatively. INTERVENTION: Anterior-posterior versus posterior-only fixation. MAIN OUTCOME MEASUREMENTS: Physical therapy (PT) clearance, discharge location, hospital length of stay (LOS), inpatient morphine equivalent doses (MED), and fracture displacement at follow-up. RESULTS: Groups were similar in demographic and injury characteristics (age, high energy mechanism, ASA score, stress displacement, and rami/sacral fracture classifications). Anterior-posterior fixation resulted in longer operative times (median difference (MD): 27.0 minutes, 95% confidence interval (CI): 17.0 to 40.0, P < 0.0001) and had a trend of increased estimated blood loss (MD: 10 mL, CI: 0 to 30, P = 0.07). Patients with anterior-posterior fixation required less inpatient MEDs (MD: -180.0, CI: -341.2 to -15.0, P = 0.02), were more likely to clear PT by discharge (100% vs. 70%, proportional difference (PD): 30%, CI: 2.0%-57.2%, P = 0.02), were less likely to discharge to rehabilitation facilities (0% vs. 30%, PD: 30%, CI: 2.0%-57.2%, P = 0.02), and had a trend of less days to clear PT after surgery (MD: -1, CI: -2 to 0, P = 0.09) and decreased LOS (MD: -1, CI: -4 to 1, P = 0.17). Late fracture displacement did not differ between groups. CONCLUSION: Anterior-posterior fixation of LC1 injuries was associated with an improved early hospital course-specifically, reduced inpatient opioid use and an increased number of patients who could clear PT and discharge home. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Concurrent Hardware Removal is Associated With Increased Odds of Infection Following Conversion Total Knee Arthroplasty.

BACKGROUND: The optimal timing of removal of periarticular implants prior to conversion total knee arthroplasty (TKA) remains to be determined. The purpose of this study was to compare infection rates in conversion TKA when hardware removal was performed in either a staged or concurrent manner. METHODS: We performed a retrospective study using a national insurance claims database of patients who underwent removal of hardware on the same day or within 1 year before their TKA. A total of 16,099 patients met the criteria. After matching, both final cohorts consisted of 4,502 patients. The 90-day and 1-year rates of prosthetic joint infection were calculated. RESULTS: The rates of infection were 1.64% and 3.00% in the staged group and 2.62% and 3.95% in the concurrent group at 90 days and 1 year postoperatively, respectively (P = .001, P = .01). Logistic regression analyses demonstrated that patients who had hardware removal greater than 3 months prior to TKA had significantly lower odds of infection at 1-year postop (Odds Ratio 0.61 95% Confidence Interval 0.45-0.84; P = .003). CONCLUSION: Removal of hardware performed concurrently or within 3 months of a TKA is associated with increased odds of prosthetic joint infection at 1 year postoperatively. Surgeons should consider removing periarticular hardware prior to TKA when possible.

The effect of pelvic ring rotation and tilt on the radiographic teardrop distance: an important consideration in the assessment of dynamic displacement on stress radiographs.

PURPOSE: The purpose of this study was to determine the effect of rotation and tilt on the radiographic teardrop distance (TD) on anteroposterior (AP) pelvis radiographs. METHODS: Radiographic examination of a pelvis models was conducted utilizing increasing degrees of beam rotation and tilt on portable C-arm fluoroscopy. The TD, x-plane rotation (symphyseal-mid-sacrum distance (SMS)), and y-plane tilt (sacroiliac joint-symphysis distance (SIS)) were measured by four independent observers. Interobserver reliability was assessed using intraclass correlations. RESULTS: TD was altered by less than 2 mm with up to 7.5° fluoroscopic rotation (SMS: 3 cm) and up to 30° of inlet and 15° of outlet (SIS: ± 3.3 cm). SMS distance effectively corresponded to the degree of rotation present (r = 1.00, CI: 0.97 to 1.00, p < 0.0001) and was strongly correlated to TD (r = -0.95, CI: -0.99 to -0.67, p = 0.001). SIS distance effectively corresponded to the degree of tilt present (r = -0.97, CI: -0.99 to -0.88, p < 0.0001) and was correlated to TD (r = 0.94, CI: 0.75 to 0.99, p = 0.0001). Linear regression models determined that, with every degree of rotation and tilt, TD was altered by 0.4 mm and 0.09 mm, respectively (p = 0.0004, r2 = 0.93 and p < 0.0001, r2 = 0.94, respectively). Interobserver reliability among observers was excellent (0.92). CONCLUSION: The TD has excellent interobserver reliability and is minimally impacted by up to 7.5° of rotation, 30° inlet tilt, and 15° of outlet tilt. Utilization of these thresholds may ensure reliability of TD measurements when assessing pelvis stress radiographs.

Expression of membrane Hsp90 is a molecular signature of T cell activation.

Heat shock protein 90 (Hsp90) maintains cellular proteostasis during stress and has been under investigation as a therapeutic target in cancer for over two decades. We and others have identified a membrane expressed form of Hsp90 (mHsp90) that previously appeared to be restricted to rapidly proliferating cells exhibiting a metastatic phenotype. Here, we used HS-131, a fluor-tethered mHsp90 inhibitor, to quantify the effect of T cell activation on the expression of mHsp90 in human and mouse T cells. In cell-based assays, stimulation of human T cells induced a 20-fold increase in mHsp90 expression at the plasma membrane, suggesting trafficking of mHsp90 is regulated by TCR and inflammatory mediated signaling. Following injection of HS-131 in mouse models of human rheumatoid arthritis and inflammatory bowel disease, we detected localization of the probe at sites of active disease, consistent with immune cell invasion. Moreover, despite rapid hepatobiliary clearance, HS-131 demonstrated efficacy in reducing the mean clinical score in the CIA arthritis model. Our results suggest mHsp90 expression on T cells is a molecular marker of T cell activation and potentially a therapeutic target for chronic diseases such as rheumatoid arthritis.

Deep learning multi-organ segmentation for whole mouse cryo-images including a comparison of 2D and 3D deep networks.

Cryo-imaging provided 3D whole-mouse microscopic color anatomy and fluorescence images that enables biotechnology applications (e.g., stem cells and metastatic cancer). In this report, we compared three methods of organ segmentation: 2D U-Net with 2D-slices and 3D U-Net with either 3D-whole-mouse or 3D-patches. We evaluated the brain, thymus, lung, heart, liver, stomach, spleen, left and right kidney, and bladder. Training with 63 mice, 2D-slices had the best performance, with median Dice scores of > 0.9 and median Hausdorff distances of < 1.2 mm in eightfold cross validation for all organs, except bladder, which is a problem organ due to variable filling and poor contrast. Results were comparable to those for a second analyst on the same data. Regression analyses were performed to fit learning curves, which showed that 2D-slices can succeed with fewer samples. Review and editing of 2D-slices segmentation results reduced human operator time from ~ 2-h to ~ 25-min, with reduced inter-observer variability. As demonstrations, we used organ segmentation to evaluate size changes in liver disease and to quantify the distribution of therapeutic mesenchymal stem cells in organs. With a 48-GB GPU, we determined that extra GPU RAM improved the performance of 3D deep learning because we could train at a higher resolution.

Concussions Increase the Odds of Lower-Extremity Injuries in National Football League Players: Four-Year Review of Publicly Available Data.

Objective: To investigate the effect of multiple concussions on the risk of lower-extremity injuries in National Football League (NFL) players. Methods: All active NFL players from September 2016 to January 2017 through September 2019 to January 2020 regular seasons were eligible for inclusion. All players who sustained multiple concussions during the study period were identified using publicly available data and included in the multiple concussion (MC) cohort. Players who sustained a single concussion (SC) as well as controls were age and position matched to the MC cohort using MEDCALC case-control. Lower-extremity injuries were then documented for the players included in all 3 cohorts. Results: The odds of sustaining a lower-extremity injury were significantly greater in the MC as well as the SC cohort when compared with the no concussion (NC)-matched cohort (odds ratio 2.92, standard deviation [SD] 1.7-4.9) and 2.28 (SD 1.5-3.6), respectively. However, we found no significant difference in the odds of sustaining a lower-extremity injury when comparing the SC with the MC cohort (odds ratio 1.00, SD 0.7-1.3). The time to lower-extremity injury after return to play from a concussion was significantly shorter in the SC group when compared with the MC group, within 1 year following a concussion injury (P = .01). Conclusions: There was a significant increase in the odds of suffering a lower-extremity injury after return to play in NFL players exposed to SC or MC when compared with age- and position-matched controls who did not sustain a concussion within the study period. There was no significant difference in the odds of suffering a lower-extremity injury after return to play for NFL players exposed to MC when compared with players exposed to a SC during our study period. Our findings suggest a potential need for injury-prevention protocols following concussion injuries. Level of Evidence: Level III, retrospective comparative prognostic trial.

Nonoperative Management of Minimally Displaced Lateral Compression Type 1 Pelvic Ring Injuries With and Without Occult Instability.

OBJECTIVES: To determine the association of pelvic fracture displacement on lateral stress radiographs (LSRs) with the hospital course of patients with minimally displaced lateral compression type 1 (LC1) pelvic injuries. DESIGN: Retrospective review. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Twenty-eight adult patients with minimally displaced (<1 cm) LC1 injuries. INTERVENTION: Nonoperative management. MAIN OUTCOME MEASUREMENTS: Delayed operative fixation, days to clear physical therapy, mobilization, hospital length of stay, and total hospital opioid morphine equivalent dose. RESULTS: LSR displacement was correlated with delayed operative fixation [r = 0.23, 95% confidence interval (CI) 0.05-1.11; P = 0.01], days to clear PT (r = 0.13, CI 0.01-0.28; P = 0.02), length of stay (r = 0.13, CI 0.006-0.26; P = 0.02), and opioid morphine equivalent dose (r = 19.4, CI 1.5-38.1; P = 0.03). A receiver operating characteristic curve for delayed operative fixation over LSR displacement had an area under the curve of 0.87. The LSR displacement threshold that maximized sensitivity and specificity for detecting patients who required delayed fixation was 10 mm (100% sensitivity and 78% specificity). Ten of the 15 patients with ≥10 mm of displacement on LSRs underwent delayed operative fixation for pain with mobilization at a median of 6 days (interquartile range 3.7-7.5). Patients with ≥10 mm of displacement on LSRs took longer to clear PT, took longer to walk 15 feet, had longer hospital stays, and used more opioids. CONCLUSIONS: LC1 fracture displacement on LSRs is associated with delayed operative fixation, difficulty mobilizing secondary to pain, longer hospital stays, and opioid use. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Magnetic resonance molecular imaging of extradomain B fibronectin enables detection of pancreatic ductal adenocarcinoma metastasis.

Extradomain-B Fibronectin (EDB-FN) is an oncomarker that can be visualized with magnetic resonance molecular imaging (MRMI) to detect pancreatic ductal adenocarcinoma (PDAC) metastasis. In this study, we sought to assess the expression of EDB-FN in clinical samples of PDAC and to evaluate MRMI of PDAC metastasis with an EDB-FN-specific gadolinium-based contrast agent (MT218) in an orthotopic KPC-GFP-Luc mouse model. EDB-FN expression was evaluated in PDAC tissue samples through immunohistochemistry. RNA-Seq data obtained from the GEPIA2 project was evaluated to demonstrate EDB-FN expression in large patient cohorts. FLASH-3D MRI at 3 T of the KPC-GFP-Luc metastasis model was performed following injection of MT218. Tumor enhancement in MR images was correlated to postmortem distribution of KPC-GFP-Luc tumors using fluorescent and bright-field cryo-imaging and anatomical landmarks. EDB-FN immunohistochemical staining scores of human metastatic tumor stroma, (2.17 ± 0.271), metastatic tumor parenchyma (2.08 ± 0.229), primary tumor stroma (1.61 ± 0.26), and primary tumor parenchyma (1.61 ± 0.12) were significantly (p < 0.0001) higher than normal pancreas stroma (0.14 ± 0.10) and normal pancreas parenchyma (0.14 ± 0.14). EDB-FN mRNA expression in tumors is 4.98 log2(TPM + 1) and 0.18 log2(TPM + 1) in normal tissue (p < 0.01). A mouse model of EDB-FN rich PDAC metastasis exhibited T1-weighted contrast to noise (CNR) changes of 21.80 ± 4.34 in perimetastatic regions and 8.38 ± 0.79 in metastatic regions identified through cryo-imaging, significantly higher (p < 0.05) than CNR changes found in normal liver (-6.43 ± 0.92), mesentery (2.24 ± 0.92), spleen (-3.06 ± 2.38) and intestine (1.08 ± 2.15). We conclude that EDB-FN is overexpressed in metastatic and primary PDAC tumors and MRMI with MT218 enables the detection of metastatic and perimetastatic tissues.

Kidney Transplant Outcomes in elderly Recipients: An Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry Study.

BACKGROUND: There is an increase in elderly patients receiving kidney transplant internationally. This study describes elderly kidney transplant recipient outcomes in Australia and New Zealand. METHODS: The study included all adult first kidney transplant recipients in Australia and New Zealand from 2000 to 2015. Survival and graft outcomes were compared between elderly (≥70 years) and younger (18-69 years) recipients using Cox proportional hazards regression. RESULTS: Overall, 10651 kidney transplant recipients were included, of which 279 (2.6%) were elderly adults. The proportion of elderly recipients increased from 0.6 to 4.4% from 2000 to 2015. Compared with younger recipients, elderly recipients were more likely to receive kidneys from deceased donors, elderly donors, and expanded criteria donors. Elderly recipients experienced poorer patient survival with 1- and 5-year survival ranging from 96% to 97% and 79% to 81%, respectively, compared with 97% to 99% and 90% 95% in younger recipients, respectively. Elderly recipients experienced comparable rates of delayed graft function and, in living donor kidney recipients, lower rates of acute rejection. CONCLUSIONS: Kidney transplantation in the elderly population is increasing. Although elderly recipients had inferior survival and graft outcomes, elderly recipients generally received poorer quality kidneys. The outcomes achieved in this cohort of elderly adults are encouraging, and improving elderly recipient outcomes should be an important focus for research.

Impact of Level of Evidence on Citation of Orthopaedic Articles.

INTRODUCTION: Level of evidence grading has become widely used in orthopaedics. This study reviewed clinical research articles published in leading orthopaedic journals to describe the association between level of evidence and number of future citations, which is one measure of an article's impact in the field. METHODS: The first 100 clinical research articles published in 2014 by each of the Journal of Bone and Joint Surgery, Clinical Orthopaedics and Related Research, and the American Journal of Sports Medicine were reviewed for level of evidence and article characteristics. Web of Science was used to identify the number of citations of each article over the following 5 years. Univariable analyses and multivariable linear regression were used to describe the associations. RESULTS: Three hundred articles were evaluated. Univariable analysis revealed no association between level of evidence and number of citations, with a median number of citations for level 1 articles of 23 (interquartile range [IQR], 14-49), level 2 articles 24 (IQR, 13-47), level 3 articles 22 (IQR, 13-40), and level 4 or 5 articles 20 (IQR, 10-36). Univariable analyses showed weak associations between other article characteristics and citations. Even after adjusting for other variables, the standardized regression coefficient for level 1 versus level 4 or 5 was only 0.14 and the overall model had a poor fit with an R2 of 0.18. CONCLUSIONS: Among clinical research articles published in leading orthopaedic journals, no notable association was found between level of evidence and future citations. CLINICAL RELEVANCE: Readers of the orthopaedic literature should understand that no association was found between level of evidence and future citations. Additional work is needed to better understand the effect level of evidence has on clinicians and researchers.

Efficacy and Safety of Mechanical IVC Filtration for Preventing Pulmonary Embolism in High-Risk Orthopedic Patients Undergoing Total Hip or Knee Arthroplasty.

BACKGROUND: To determine the efficacy and safety of inferior vena cava (IVC) filters in preventing pulmonary embolism (PE) in high-risk patients undergoing hip or knee arthroplasty. METHODS: 2857 hip or knee arthroplasty procedures between January 2013 and December 2018 were retrospectively reviewed. Patients with a preoperative history of venous thromboembolism (VTE), either PE or deep venous thrombosis (DVT), were categorized as high-risk patients. The incidence of overall VTE, PE, and DVT were compared between patients with filters and those without. The subgroup analysis was also performed by patient risk, and filter status and the incidence of VTE, PE, and DVT were compared. Variables such as filter placement, history of hypercoagulability etcetra were evaluated as risk factors for the development of postoperative VTE. RESULTS: In the high-risk group, the use of IVC filters was significantly associated with a lower incidence of pulmonary embolism (0.8% vs 5.5%, P = .028). When compared with the low-risk group, the high-risk group had significantly higher incidence of PE (3.8% vs 2.0%, P = .038), DVT (11.6% vs 5.3%, P < .001), and overall VTE (15.0% vs 6.8%, P < .001). The history of VTE was associated with postoperative VTE (P < .001), PE (P = .042), and DVT (P < .001). There was no significant correlation between filter placement and postoperative VTE, DVT, or PE in the low-risk group. Filter retrieval was successful in 100% (96/96) of attempted patients with no complications. CONCLUSION: The use of IVC filters is significantly associated with a lower incidence in pulmonary embolism in high-risk arthroplasty patients. High-risk patients demonstrated an incidence of postoperative VTE over two times greater than other patients. Prophylactic placement of IVC filters in hip/knee arthroplasty is safe.

Opioid Naive Surgeons and Opioid-Tolerant Patients: Can Education Alter Prescribing Patterns to Total Knee Arthroplasty Patients?

Patterns of opioid overprescribing following arthroplasty likely developed given that poor pain control can diminish patient satisfaction, delay disposition, and lead to complications. Recently, interventions promoting responsible pain management have been described, however, most of the existing literature focuses on opioid naive patients. The aim of this study was to describe the effect of an educational intervention on opioid prescribing for opioid-tolerant patients undergoing primary total knee arthroplasty (TKA). As the start to a quality improvement initiative to reduce opioid overprescribing, a departmental grand rounds was conducted. Prescribing data, for the year before and after this intervention, were retrospectively collected for all opioid-tolerant patients undergoing primary TKA. Opioid prescribing data were standardized to mean morphine milligram equivalents (MME). Segmented time series regression was utilized to estimate the change in opioid prescribing associated with the intervention. A total of 508 opioid-tolerant patients underwent TKA at our institution during the study period. The intervention was associated with a statistically significant decrease of 468 mean MME (23%) from 2,062 to 1,594 (p = 0.005) in TKA patients. This study demonstrates that an educational intervention is associated with decreased opioid prescribing among opioid-tolerant TKA patients. While the effective management of these patients is challenging, surgeon education should be a key focus to optimizing their care.

Dupilumab as Add-on Therapy for Chronic Rhinosinusitis With Nasal Polyposis in Aspirin Exacerbated Respiratory Disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) affects 7% of asthmatics. Usual therapies are inadequate for asthma and/or nasal polyposis, leading to decreased quality of life. OBJECTIVE: Our objective was to evaluate the efficacy of dupilumab in AERD patients with uncontrolled, chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: Patients 18 years and older with a physician diagnosis of AERD and sino-nasal outcome test 22 (SNOT 22) score ≥19 despite standard medical therapy were eligible for the study. Patients received one month of placebo dosing, followed by 6 months of dupilumab. Patients were blinded to the order of therapy. Wilcoxon-paired rank sum test was used to compare study outcomes at baseline and the completion of the study. RESULTS: Ten patients completed the study. The median baseline SNOT 22 score improved from 46 [IQR: 34 to 64.8] to 9.5 [IQR: 2.5 to 19] after 6 months of therapy (p = 0.0050). The median baseline Lund MacKay score improved from 21.5 [IQR: 17 to 23.3] to 4 [IQR: 1.2 to 6] after 6 months of therapy (p = 0.0050). There was also improvement in the following secondary outcomes: asthma control test (ACT), mini asthma quality of life questionnaire (AQLQ), and University of Pennsylvania Smell Identification test (UPSIT). Exhaled nitric oxide (FeNO), total serum IgE, 24-hour urinary leukotriene E4, and serum thymus and activation regulated cytokine (TARC) also decreased. There were no significant study-related adverse events. CONCLUSION: Dupilumab was highly effective as add-on therapy for CRSwNP in AERD, improving patient-reported outcomes, sinus opacification, and markers of T2 inflammation.