Effects of long-term high dose aspartame on body mass, bone strength, femoral geometry, and microbiota composition in a young and aged cohort of male and female mice.

Background: Recent reassessment of the safety of aspartame has prompted increased evaluation of its effect on the health of a range of tissues. The gut microbiome is altered by oral aspartame. One prior study suggested that changes in the microbiome caused by aspartame could influence the strength of bone in young skeletally developing mice. Here we ask how aspartame influences bone in mice of different age and sex. Objective: The objective of this study was to determine the effect of aspartame on the bone strength and gut microbiota of young and aged mice. Methods: Male and female C57Bl/6J mice were untreated or treated with a high dose of aspartame in their drinking water from 1 month of age until 4 (young cohort; n = 80) or 22 months (aged cohort; n = 52). Results: In aged males, mice treated with aspartame had greater body mass, whole bone strength, and femoral geometry relative to untreated. Specifically, in aged males, aspartame led to 9% increase in body mass (p < 0.001), 22% increase in whole bone strength (p = 0.006), and 17% increase in section modulus (p < 0.001) relative to untreated mice. Aged males and females receiving aspartame had a different microbiota than untreated mice and a decreased abundance of Odoribacter. No differences in body mass, whole bone strength, or femoral geometry were associated with aspartame dosing in young males or young or aged females. Conclusions: Aspartame treated aged males had greater whole bone strength and the effect appeared to be explained by greater body mass. Aspartame treatment did not alter whole bone strength in young males or young or aged females despite the aspartame having a similar effect on the microbiota of both aged males and females.

Increasing Hip Arthroscopy Case Volume Is Associated With Increased Risk for Revision Surgery but Not Conversion to Total Hip Arthroplasty or 90-Day Hospitalizations: A Cross-Sectional Analysis of 468 Surgeons.

PURPOSE: To analyze the effects of surgeon-specific factors, including case volume, career duration, fellowship training, practice type, and region of practice, on rates of 2-year revision surgery, conversion to total hip arthroplasty (THA), and 90-day hospitalizations following hip arthroscopy. METHODS: The PearlDiver Mariner Database was used to query patients undergoing hip arthroscopy between 2015 and 2018. Surgeons performing these procedures were identified, and surgeon-specific demographics and variables were collected from publicly available data. Patients were followed for 2 years to assess for reoperations, including revision hip arthroscopy and conversion to THA, as well as 90-day hospitalizations, including emergency department visits and hospital readmissions. International Classification of Diseases, Tenth Revision codes were used to track the laterality of revision hip procedures. Associations between surgeon-specific factors and postoperative outcomes were assessed through univariate and multivariate analyses. RESULTS: In total, 20,834 patients underwent hip arthroscopy procedures by 468 surgeons. Multivariate analysis with logistic regression adjusted for patient-related factors (age, sex, obesity, Charlson Comorbidity Index, and smoking status) identified increasing surgeon case volume to be associated with increased risk for 2-year revision hip arthroscopy (P < .001), but not 2-year conversion to THA or 90-day hospitalizations. Nonsports medicine fellowship-trained surgeons were associated with greater risk for 2-year THA conversion (P < .001) and 90-day hospital readmissions (P < .01). Surgeons practicing in an academic setting demonstrated greater risk for 90-day hospital readmissions (P < .001). Surgeons practicing in the West region of the United States were more likely to incur 2-year revision hip arthroscopy procedures compared to surgeons in the South, Midwest or Northeast (P < .001). CONCLUSIONS: Increasing surgeon hip arthroscopy case volume is associated with an increased risk for 2-year revision hip arthroscopy but not conversion to THA or 90-day hospitalizations. Further, non-sports medicine fellowship-trained surgeons were associated with higher risk for 2-year THA conversion after hip arthroscopy. LEVEL OF EVIDENCE: Level III, retrospective cohort analysis.

Monoclonal Antibody Disrupts Biofilm Structure and Restores Antibiotic Susceptibility in an Orthopedic Implant Infection Model.

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.

#OrthoTwitter: Relationship Between Author Twitter Utilization and Academic Impact in Orthopaedic Surgery.

Background #OrthoTwitter has evolved to disseminate findings and engage the public. However, the academic impact of Twitter utilization in orthopaedic surgery is unknown. Questions/purposes The purpose of the study was to evaluate relationships between the author and manuscript Twitter activity and citations. Methods Manuscripts in 17 orthopaedic journals from 2018 were identified. Citations, online mentions, impact factors, and subspecialties were obtained. H-index and Twitter account details for authors were obtained for a subset of manuscripts. Relationships between Twitter activity and citations were evaluated. Results 2,473/4,224 (58.5%) manuscripts were mentioned on Twitter (n=29,958 mentions), with Twitter manuscripts cited more frequently (median 10 vs. 7, p<0.0001). Twitter mentions, impact factors, non-open-access status, and subspecialties were associated with citation counts. Articles mentioned in 10, 100, and 1,000 Tweets were observed to have a 1.1-fold, 1.7-fold, and 245-fold increase in citations. In author-level analyses, 156 (20.0%) first and 216 (27.7%) senior authors had Twitter accounts. Citation count was associated with increasing senior author H-index (ß est=0.13, p<0.05), Twitter mentions (ß est=0.0043, p<0.0001), impact factors (ß est=0.13, p<0.0001), and having a first (ß est=0.20, p<0.05) or senior author (ß est=0.17, p<0.05) on Twitter. Articles published in arthroplasty (ß est=0.49, p<0.05), general interest (ß est=0.55, p<0.01), sports (ß est=0.63, p<0.01), and non-open access journals (ß est=0.41, p<0.001) were cited more. H-index correlated with followers for first (rho=0.31, p<0.0001) and senior authors (rho=0.44, p<0.0001). Conclusion Author Twitter utilization is independently associated with manuscript citations. Authors should be aware of the potential association between social media utilization and traditional academic impact. Understanding the relationship between social media utilization and academic impact is necessary to effectively disseminate research.

Delayed ACL reconstruction increases rates of concomitant procedures and risk of subsequent surgery.

PURPOSE: To utilise a large cross-sectional database to analyse the effects of time duration between diagnosis of anterior cruciate ligament (ACL) tear and ACL reconstruction (ACLR) on concomitant procedures performed and subsequent surgery within 2 years. METHODS: An analysis from 2015 to 2018 was performed using the Mariner PearlDiver Patient Records Database. Current Procedural Terminology (CPT), and International Classification of Diseases (ICD-10) codes identified patients with a diagnosis of ACL tear who underwent subsequent ACLR. Patients were stratified in biweekly and bimonthly increments based on the time duration between initial diagnosis of ACL tear and surgical treatment. Chi-squared analysis was used to compare categorical variables, and trend analysis was performed with Cochran-Armitage independence testing. RESULTS: Of 11,867 patients who underwent ACLR, 76.1% underwent surgery within 2 months of injury diagnosis. Patients aged 10-19 were most likely to undergo surgery within 2 months of injury diagnosis (83.5%, P < 0.0001). As duration from injury diagnosis to ACLR increased from < 2 months to > 6 months, rates of concomitant meniscectomy increased from 9.1% to 20.5% (P < 0.0001). The overall 2-year subsequent surgery rate was 5.3%. The incidence of revision ACLR was highest for patients who underwent surgery > 6 months after diagnosis (P < 0.0001), whilst the incidence of ipsilateral lysis of adhesions and manipulation under anaesthesia (MUA) was highest for patients who underwent surgery < 2 months after diagnosis (P < 0.0001). ACLR at 6-8 weeks after diagnosis demonstrated the lowest risk for concomitant procedures as well as 2-year subsequent surgery. CONCLUSION: The majority of patients undergo ACL reconstruction within 2 months of initial ACL tear diagnosis. Delayed surgery greater than 6 months after the diagnosis of an ACL rupture leads to increased need for concomitant meniscectomy as well as higher risk for revision ACLR within 2 years, but immediate surgery may increase risk for knee arthrofibrosis. LEVEL OF EVIDENCE: IV.

Risk for recurrent instability and reoperation following arthroscopic and open shoulder stabilization in a large cross-sectional population.

Background: Recurrent shoulder instability is an orthopedic problem with potentially long-term functional ramifications. Although arthroscopic stabilization has become increasingly utilized over open stabilization, optimal surgical intervention to minimize recurrent instability remains controversial. Methods: The PearlDiver Mariner database was queried for all cases of open and arthroscopic shoulder stabilization from 2010 to 2019. Utilization trends were aggregated after identifying cohorts of 107,210 and 13,217 patients who respectively underwent arthroscopic or open stabilization using Current Procedural Terminology codes. Subsets from those cohorts with laterality-specific International Classification of Diseases, Tenth Revision codes for shoulder instability were used to evaluate 2-year rates of recurrent instability (presence of shoulder dislocation or revision open or arthroscopic stabilization). Linear regression and chi-squared analysis were used to analyze utilization trends and to compare recurrent instability. Results: Arthroscopic stabilization comprised 90% of all stabilization procedures with annual utilization continuing to increase into 2019. Latarjet utilization increased from 15% to 42% of all open stabilization procedures while open Bankart repair utilization decreased from 56% to 35%. The rate of recurrent instability was 10.2% after arthroscopic stabilization and 12.3% after open stabilization (P = .01). Rates of redislocation (4.0% vs. 2.6%, P < .01), conversion to shoulder arthroplasty (1.2% vs. 0.4%, P < .01), and revision open stabilization (6.8% vs. 2.3%, P < .01) after index open stabilization were significantly higher than after index arthroscopic stabilization. There was no difference in revision stabilization or dislocation rates between open procedures. Conclusion: Despite increasing utilization of coracoid transfer, arthroscopic stabilization is still the dominant modality used for surgical treatment of shoulder instability and in our analysis, showed lower 2-year rates of dislocation, revision open stabilization, and conversion to shoulder arthroplasty.

The Utility of Virtual Reality in Orthopedic Surgical Training.

OBJECTIVE: To examine the efficacy of virtual reality (VR) to prepare surgical trainees for a pediatric orthopedic surgery procedure: pinning of a slipped capital femoral epiphysis (SCFE). DESIGN: Participants were randomly assigned to a standard, study guide (SG) group or to a VR training group. All participants were provided a technique video and SG; the VR group additionally trained via an Osso VR surgical trainer (ossovr.com) with real-time feedback and coaching from an attending pediatric orthopedic surgeon. Following training, participants performed a SCFE guidewire placement on a SawBones model embedded in a soft-tissue envelope (SawBones model 1161). Participants were asked to achieve "ideal placement" based on the training provided. Participants were evaluated on time, number of pin "in-and outs," penetration of the articular surface, angle between the pin and the physis, distance from pin tip to subchondral bone and distance from the center-center point of the epiphysis. SETTING: Orthopedic Institute for Children, Los Angeles, CA. PARTICIPANTS: Twenty fourth-year medical students, first- and second-year orthopedic residents without experience with the SCFE procedure. RESULTS: Twenty participants were randomized to SG (n = 10) or VR (n = 10). Average time to final pin placement was 19% shorter in VR group (706 vs 573 seconds, p = 0.26). When compared to SG, the VR group had, on average, 70% less pin in-and-outs (1.7 vs 0.5, p = 0.28), 50% less articular surface penetrations (0.4 vs 0.2, p = 0.36), and 18% smaller distance from pin tip to subchondral bone on lateral view (7.1 vs 5.8 mm, p = 0.42). Moreover, the VR group had a lower average angle deviation between pin and line perpendicular to the physis on coronal view (4.9° vs 2.5°, p < 0.05). CONCLUSIONS: VR training is potentially more effective than traditional preparatory methods. This pilot study suggests that VR training may be a viable surgical training tool, which may alleviate constraints of time, money, and safety concerns with resultant broad applicability for surgical education.

Younger Patients Are More Likely to Undergo Arthroscopic Meniscal Repair and Revision Meniscal Surgery in a Large Cross-Sectional Cohort.

PURPOSE: To evaluate recent trends in the treatment of meniscal tears with arthroscopic repair and debridement and to assess revision surgery within 2 years using a large cross-sectional database. METHODS: Patients with a diagnosis of meniscal tear from 2010 to 2017 were queried using the Mariner data set from PearlDiver. Patient demographic data were analyzed and tracked via International Classification of Diseases, Tenth Revision codes to investigate subsequent ipsilateral meniscal procedures and conversion to total knee arthroplasty within 2 years after index meniscal surgery. RESULTS: Of the 1,383,161 patients with a diagnosis of meniscal tear, 53.0% underwent surgical treatment. Surgical treatment consisted of meniscal debridement in 96.6% of patients and meniscal repair in 3.4%. The percentage of meniscal repairs increased from 2.7% to 4.4% over the 8-year period evaluated, whereas the percentage of meniscal debridement decreased from 97.3% to 95.6% (P < .0001). Younger patients were more likely to undergo meniscal repair (23% of those aged 10-19 years) than older patients (<1% of those aged ≥60 years). Among the 191,729 patients with International Classification of Diseases, Tenth Revision coding and 2-year follow-up, 10.6% of patients with index meniscal repair required a revision meniscal operation and 1.2% underwent conversion to arthroplasty. Subsequent meniscal procedures within 2 years after index meniscal repair included meniscal debridement in 81.6% of patients and revision repair in 18.4%. Patients who initially underwent meniscal debridement were less likely to undergo revision meniscal surgery (5.1%), but 4.7% required conversion to arthroplasty. Patients aged 10 to 19 years were most likely to undergo revision meniscal procedures after both index meniscal repair (12.8%) and meniscal debridement (8.8%). CONCLUSIONS: The rate of meniscal repair is increasing over time, with patients younger than 30 years most likely to undergo repair for a meniscal tear. Revision surgery for meniscal repair or debridement is more common in adolescents and patients who undergo an index meniscal repair. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Evaluating Utilization Trends in Adhesive Capsulitis of the Shoulder: A Retrospective Cohort Analysis of a Large Database.

BACKGROUND: Nonoperative and operative treatment modalities have been used for symptom management of adhesive capsulitis, but neither has been shown to significantly alter the long-term natural history. PURPOSE/HYPOTHESIS: The purpose was to evaluate the current trends in resource and treatment strategy utilization for patients with adhesive capsulitis. It was hypothesized that (1) patients with idiopathic adhesive capsulitis will primarily undergo nonoperative treatment and (2) patients with systemic medical comorbidities will demonstrate relatively higher utilization of nonoperative therapies. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We searched the Mariner/PearlDiver database for Current Procedural Terminology and International Classification of Diseases codes to identify patients with adhesive capsulitis from 2010 to 2020 and to track their usage of diagnostic and therapeutic modalities, including radiography, magnetic resonance imaging (MRI), physical therapy, surgery, opioids, and injection. Patients with active records 1 year before and 2 years after initial diagnosis of adhesive capsulitis were eligible. Excluded were patients with secondary causes of adhesive capsulitis, such as fracture, infection, prior surgery, or other intra-articular pathology. RESULTS: The median age of this 165,937-patient cohort was 58 years, with 67% being women. There was a high prevalence of comorbid diabetes (44.2%), thyroid disorder (29.6%), and Dupuytren contracture (1.3%). Within 2 years of diagnosis of adhesive capsulitis, diagnostic and therapeutic modality utilization included radiography (47.2%), opioids (46.7%), physical therapy (43.1%), injection (39.0%), MRI (15.8%), arthroscopic surgery (2.7%), and manipulation under anesthesia (2.5%). Over 68% of the diagnostic and therapeutic modalities were rendered from 3 months before to 3 months after diagnosis. Patients with diabetes, thyroid disorders, tobacco use, and obesity had greater odds for treatment with physical therapy, opioids, radiography, and injection when compared with patients without these comorbidities (odds ratio [OR] range, 1.05-2.21; P < .0001). Patients with diabetes and thyroid disorders had decreased odds for surgery (OR range, 0.88-0.91; P ≤ .003). Patients with Dupuytren contracture had increased odds for all therapeutic modalities (OR range, 1.20-1.68; P < .0001). CONCLUSION: Patients with adhesive capsulitis underwent primarily nonoperative treatment, with a high percentage utilizing opioids. The most active periods for treatment were from 3 months before diagnosis to 3 months after, and patients with medical comorbidities were more likely to undergo nonoperative treatment.

Biceps Tenodesis Demonstrates Lower Reoperation Rates Compared to SLAP Repair for Treatment of SLAP Tears in a Large Cross-Sectional Population.

PURPOSE: To use a contemporary cross-sectional data set to evaluate trends in surgical treatment for superior labrum anterior and posterior (SLAP) tears and compare surgical outcomes with respect to 2-year revision surgery rates following index SLAP repair versus biceps tenodesis (BT). METHODS: Patients diagnosed with a SLAP tear between 2010 and 2017 were queried using the Mariner PearlDiver database and stratified by demographic variables and surgical treatment with arthroscopic SLAP repair or arthroscopic/open BT. From 2015 to 2017, Current Procedural Terminology (CPT) and International Classification of Diseases 10th revision (ICD-10) codes were used to track ipsilateral subsequent reoperation within 2-years of index surgery. RESULTS: Between 2010 to 2017, 16.6% of 377,463 patients diagnosed with a SLAP tear underwent surgery (62.3% SLAP repair vs 37.7% BT). 52.4% of BT procedures were arthroscopic (47.6% open). The frequency of SLAP repairs decreased from 74.0% to 46.2% (61%), while the frequency of BTs increased from 26.0% to 53.8% (202%) during the study period. Patients under age 50 were more likely to undergo SLAP repair, and those undergoing BT were more likely to be over 50 with higher CCI and comorbidity risk. 6.3% of 16,186 patients identified with ICD-10 coding required reoperation within 2-years postoperatively. SLAP repair demonstrated a higher revision rate (6.8%; 95% CI, 6.3-7.4%) than BT (5.7%; 95% CI, 5.2-6.2%; P =.0002), (open 5.8% vs arthroscopic BT 5.5%). Arthroscopic debridement, including biceps tenotomy, revision SLAP repair, and revision BT were the most common subsequent procedures. Patients aged 40 to 49 had the highest rate of revision surgery (7.8%). CONCLUSIONS: The treatment trend for SLAP tears is changing, with SLAP repair becoming significantly less utilized and BT now becoming the preferred option, especially in patients over 50. Arthroscopic and open BT demonstrated slightly lower risk for reoperation than SLAP repair. LEVEL OF EVIDENCE: IV, cross-sectional study.

Contemporary Practice Patterns for the Treatment of Anterior Cruciate Ligament Tears in the United States.

BACKGROUND: There is a lack of research investigating current practice trends in the treatment of anterior cruciate ligament (ACL) tears as well as common concomitant procedures and reoperations associated with ACL reconstruction (ACLR). PURPOSE: To analyze current practice patterns for ACLR as well as the frequency of concomitant and revision procedures with respect to patient characteristics in a cross-sectional population of the United States. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patient data between 2010 and 2017 were queried using the Mariner PearlDiver database. International Classification of Diseases, Ninth Revision (in 2010-2014) and Tenth Revision (ICD-10; in 2015-2017), diagnosis codes were used to identify ACL tears, and Current Procedural Terminology codes were used to identify ACLR and concomitant surgical procedures. Patient characteristics were stratified by sex and age. Cases of subsequent knee surgery and conversion to total knee arthroplasty (TKA) within 2 years after ACLR were tracked using ICD-10 codes between 2015 and 2017 to ensure ipsilateral laterality. RESULTS: Of 229,295 patients identified with an ACL tear diagnosis during the study period, 75% underwent ACLR. In patients aged 10 to 39 years, 84% to 92% underwent ACLR, while patients aged 50 to 59 (50%) and 60 to 69 (28%) years were less likely to have surgery after an ACL tear. Female and male patients underwent ACLR at a similar rate (75%). Within the patients who underwent ACLR, 44% underwent concomitant meniscal debridement as compared with 11% with concomitant meniscal repair. Male patients were more likely to undergo meniscal debridement (48% vs 40%; P < .0001). The frequency of meniscal repair increased from 9% in 2010 to 14% in 2017, while the frequency of meniscal debridement decreased from 47% to 41% (P < .0001). Within 2 years of ACLR, 6% of patients underwent revision ACLR; 4%, subsequent meniscal debridement; 1%, meniscal repair; and 1%, conversion to TKA. CONCLUSION: The frequency of ACLR for ACL tears has remained relatively stable in recent years and was similar between female and male patients in this cross-sectional population. The majority of patients aged 10 to 39 years underwent ACLR, while less than half of patients >50 years underwent surgery.

Active rheumatoid arthritis in a mouse model is not an independent risk factor for periprosthetic joint infection.

INTRODUCTION: Periprosthetic joint infection (PJI) represents a devastating complication of total joint arthroplasty associated with significant morbidity and mortality. Literature suggests a possible higher incidence of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA). There is, however, no consensus on this purported risk nor a well-defined mechanism. This study investigates how collagen-induced arthritis (CIA), a validated animal model of RA, impacts infectious burden in a well-established model of PJI. METHODS: Control mice were compared against CIA mice. Whole blood samples were collected to quantify systemic IgG levels via ELISA. Ex vivo respiratory burst function was measured via dihydrorhodamine assay. Ex vivo Staphylococcus aureus Xen36 burden was measured directly via colony forming unit (CFU) counts and crystal violet assay to assess biofilm formation. In vivo, surgical placement of a titanium implant through the knee joint and inoculation with S. aureus Xen36 was performed. Bacterial burden was then quantified by longitudinal bioluminescent imaging. RESULTS: Mice with CIA demonstrated significantly higher levels of systemic IgG compared with control mice (p = 0.003). Ex vivo, there was no significant difference in respiratory burst function (p = 0.89) or S. aureus bacterial burden as measured by CFU counts (p = 0.91) and crystal violet assay (p = 0.96). In vivo, no significant difference in bacterial bioluminescence between groups was found at all postoperative time points. CFU counts of both the implant and the peri-implant tissue were not significantly different between groups (p = 0.82 and 0.80, respectively). CONCLUSION: This study demonstrated no significant difference in S. aureus infectious burden between mice with CIA and control mice. These results suggest that untreated, active RA may not represent a significant intrinsic risk factor for PJI, however further mechanistic translational and clinical studies are warranted.

Platelet Deficiency Represents a Modifiable Risk Factor for Periprosthetic Joint Infection in a Preclinical Mouse Model.

BACKGROUND: Well known for their hemostatic function, platelets are increasingly becoming recognized as important immunomodulators. The purpose of the present study was to assess the impact of platelet depletion on antimicrobial host defense in a mouse model of periprosthetic joint infection (PJI). METHODS: Thrombocytopenia (TCP) was induced in C57BL/6 mice with use of a selective antibody against platelet CD41 (anti-CD41). Whole blood from pre-treated mice was incubated with Staphylococcus aureus to assess antimicrobial efficacy with use of bioluminescent imaging, quantitative histological staining, and colony forming unit (CFU) quantification. In parallel, untreated heterologous platelets were added to TCP blood to assess potential rescue of antimicrobial efficacy. In vivo, TCP and control mice underwent placement of a titanium implant in the femur inoculated with bioluminescent Xen36 S. aureus. Longitudinal bioluminescent imaging was performed postoperatively to quantify the evolution of bacterial burden, which was confirmed via assessment of S. aureus CFUs on the implant and in peri-implant tissue on postoperative day (POD) 28. RESULTS: Anti-CD41 treatment resulted in significant dose-dependent reductions in platelet count. Ex vivo, platelet-depleted whole blood demonstrated significantly less bacterial reduction than control blood. These outcomes were reversed with the addition of untreated rescue platelets. In vivo, infection burden was significantly higher in TCP mice and was inversely correlated with preoperative platelet count (r2 = 0.63, p = 0.037). Likewise, CFU quantification on POD28 was associated with increased bacterial proliferation and severity of periprosthetic infection in TCP mice compared with controls. CONCLUSIONS: Thrombocytopenia resulted in an increased bacterial burden both ex vivo and in vivo in a mouse model of PJI. CLINICAL RELEVANCE: In orthopaedic patients, deficiencies in platelet quantity or function represent an easily modifiable risk factor for PJI.

Hip Arthroscopy Volume and Reoperations in a Large Cross-Sectional Population: High Rate of Subsequent Revision Hip Arthroscopy in Young Patients and Total Hip Arthroplasty in Older Patients.

PURPOSE: To report contemporary trends in hip arthroscopy case volume in the United States using a large cross-sectional cohort with accurate laterality tracking for assessment of revision surgery and rates of conversion to total hip arthroplasty (THA). METHODS: Using Current Procedural Terminology codes, we queried the Mariner PearlDiver dataset for patients who underwent hip arthroscopy from 2010 to 2017. Patient demographics were recorded and subsequent hip arthroscopy procedures and THA conversion within 2 years after surgery were tracked using International Classification of Diseases, Tenth Revision codes to accurately identify laterality. Emergency department and hospital admission within 30 days after surgery were queried. RESULTS: Of the 53,103 patients undergoing hip arthroscopy procedures, hip arthroscopy case volume increased 2-fold from 2010 to 2014 but remained relatively unchanged from 2014 to 2017. The most common age group undergoing surgery was 40 to 49 years, and female patients represented 70% of cases. Two-year subsequent surgery rate was 19%, with 15.1% undergoing a revision arthroscopy and 3.9% converting to THA. The most common revision arthroscopy procedures were femoroplasty (9.5%), labral repair (8.5%), and acetabuloplasty (4.3%). Younger patients were more likely to undergo revision arthroscopy (18% age 10-19 years; 15% age 20-29 years). Older patients had a significant risk for conversion to THA within 2 years (36% age 60-69 years; 28% age 50-59 years). Female patients also demonstrated a slightly greater rate of conversion to THA (4.1% female, 3.5% male, P <.0001). Patients 20 to 29 years had the greatest risk of emergency department admission (5.4%) and hospital admission (0.8%) within 30 days of surgery. CONCLUSIONS: The rise in hip arthroscopy procedures may be starting to plateau in the United States. Cross-sectional data also indicate that there is a greater than previously reported rate of revision hip arthroscopy in patients younger than 30 years of age and conversion to THA in patients older than 50 years of age. LEVEL OF EVIDENCE: III, cross-sectional study.

Arthroscopic Rotator Cuff Repair Results in Lower Two-Year Reoperation Rates Compared With Open Rotator Cuff Repair in a Large Cross-sectional Cohort.

PURPOSE: To use a large, contemporary database to perform a cross-sectional analysis of current practice trends in rotator cuff repair (RCR) for the treatment of full-thickness rotator cuff tear (RCT) and determine outcomes of arthroscopic and open RCR, including hospital readmissions and 2-year reoperation rates with accurate laterality tracking using International Classification of Diseases, Tenth Revision (ICD-10) codes. METHODS: The PearlDiver Mariner dataset was used to query patients with full-thickness RCTs from 2010 to 2017. Propensity-score matching was performed to account for differences in age and comorbidities and allow for comparison between those undergoing open RCR and arthroscopic RCR. Subsequent procedures were tracked using ICD-10 codes to identify ipsilateral surgery within 2 years of index surgery. Hospital and emergency department admission within 30 days of surgery were investigated. RESULTS: Of 534,076 patients diagnosed with full-thickness RCT, 37% underwent RCR; 73% of which were arthroscopic. From 2010 to 2017, arthroscopic RCRs increased from 65% to 80%, whereas open RCRs decreased from 35% to 20% (P < .0001). Younger patients underwent arthroscopic RCR more frequently, and patients who underwent open RCR had greater rates of 30-day emergency department (7.0%) and hospital readmission (2.0%) compared with arthroscopic RCR (6.3%, 1.0%, respectively) (P < .0001). For 24,392 patients with ICD-10 coding and 2-year follow-up, 10.4% of patients required reoperation, with the most common procedure being revision RCR, and 1.3% required conversion to arthroplasty. Open RCRs were more likely to require subsequent surgery (11.3%) compared with arthroscopic RCR (9.5%) (P < .0001). Patients aged 50 to 59 had the greatest rate of reoperation (14.0%), but no patients younger than age 40 years required reoperation, and no patients younger than age 50 years required conversion to arthroplasty. CONCLUSIONS: The frequency of arthroscopic RCR has continued to increase compared to open RCR. In this large cross-sectional analysis, arthroscopic RCR demonstrated lower 2-year reoperation rates and 30-day readmission rates compared to open RCR. LEVEL OF EVIDENCE: III, cross-sectional study.

Inhibition of Angiotensin Converting Enzyme Impairs Anti-staphylococcal Immune Function in a Preclinical Model of Implant Infection.

Background: Evidence suggests the renin-angiotensin system (RAS) plays key immunomodulatory roles. In particular, angiotensin-converting enzyme (ACE) has been shown to play a role in antimicrobial host defense. ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) are some of the most commonly prescribed medications, especially in patients undergoing invasive surgery. Thus, the current study assessed the immunomodulatory effect of RAS-modulation in a preclinical model of implant infection. Methods:In vitro antimicrobial effects of ACEi and ARBs were first assessed. C57BL/6J mice subsequently received either an ACEi (lisinopril; 16 mg/kg/day), an ARB (losartan; 30 mg/kg/day), or no treatment. Conditioned mice blood was then utilized to quantify respiratory burst function as well as Staphylococcus aureus Xen36 burden ex vivo in each treatment group. S. aureus infectious burden for each treatment group was then assessed in vivo using a validated mouse model of implant infection. Real-time quantitation of infectious burden via bioluminescent imaging over the course of 28 days post-procedure was assessed. Host response via monocyte and neutrophil infiltration within paraspinal and spleen tissue was quantified by immunohistochemistry for F4/80 and myeloperoxidase, respectively. Results: Blood from mice treated with an ACEi demonstrated a decreased ability to eradicate bacteria when mixed with Xen36 as significantly higher levels of colony forming units (CFU) and biofilm formation was appreciated ex vivo (p < 0.05). Mice treated with an ACEi showed a higher infection burden in vivo at all times (p < 0.05) and significantly higher CFUs of bacteria on both implant and paraspinal tissue at the time of sacrifice (p < 0.05 for each comparison). There was also significantly decreased infiltration and respiratory burst function of immune effector cells in the ACEi group (p < 0.05). Conclusion: ACEi, but not ARB, treatment resulted in increased S. aureus burden and impaired immune response in a preclinical model of implant infection. These results suggest that perioperative ACEi use may represent a previously unappreciated risk factor for surgical site infection. Given the relative interchangeability of ACEi and ARB from a cardiovascular standpoint, this risk factor may be modifiable.

In vivo Mouse Model of Spinal Implant Infection.

Spine implant infections portend poor outcomes as diagnosis is challenging and surgical eradication is at odds with mechanical spinal stability. The purpose of this method is to describe a novel mouse model of spinal implant infection (SII) that was created to provide an inexpensive, rapid, and accurate in vivo tool to test potential therapeutics and treatment strategies for spinal implant infections. In this method, we present a model of posterior-approach spinal surgery in which a stainless-steel k-wire is transfixed into the L4 spinous process of 12-week old C57BL/6J wild-type mice and inoculated with 1 x 103 CFU of a bioluminescent strain of Staphylococcus aureus Xen36 bacteria. Mice are then longitudinally imaged for bioluminescence in vivo on post-operative days 0, 1, 3, 5, 7, 10, 14, 18, 21, 25, 28, and 35. Bioluminescence imaging (BLI) signals from a standardized field of view are quantified to measure in vivo bacterial burden. To quantify bacteria adhering to implants and peri-implant tissue, mice are euthanized and the implant and surrounding soft tissue are harvested. Bacteria are detached from the implant by sonication, cultured overnight and then colony forming units (CFUs) are counted. The results acquired from this method include longitudinal bacterial counts as measured by in vivo S. aureus bioluminescence (mean maximum flux) and CFU counts following euthanasia. While prior animal models of instrumented spine infection have involved invasive, ex vivo tissue analysis, the mouse model of SII presented in this paper leverages noninvasive, real time in vivo optical imaging of bioluminescent bacteria to replace static tissue study. Applications of the model are broad and may include utilizing alternative bioluminescent bacterial strains, incorporating other types of genetically engineered mice to contemporaneously study host immune response, and evaluating current or investigating new diagnostic and therapeutic modalities such as antibiotics or implant coatings.

Novel in vivo mouse model of shoulder implant infection.

BACKGROUND: Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided débridement. METHODS: A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 µL of 1 × 103 (e3), or 1 × 104 (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 µL sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed. RESULTS: Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P < .001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence. DISCUSSION: Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII. CONCLUSION: The development of this model provides a foundation to study new therapeutics, interventions, and host modifications.

Randomized Trial of a Virtual Reality Tool to Teach Surgical Technique for Tibial Shaft Fracture Intramedullary Nailing.

INTRODUCTION: Active learning methods have accumulated popularity due to improved results in knowledge acquisition as opposed to passive learning methods. For surgical resident physicians with limited training opportunities outside of the operating room due to time constraints, virtual reality (VR) is a relatively inexpensive and time-efficient active training method for procurement of surgical skills. We conducted a simulated intramedullary nailing (IMN) of a tibia to demonstrate VR training programs as a more effective modality of learning orthopedic surgical techniques compared to passive learning tools such as a standard guide (SG) through trained novice medical students performing a SawBones simulation of intramedullary nail fixation. MATERIALS AND METHODS: First and second-year medical students without prior experience of procedure were recruited and randomized to SG or VR training. Participants were observed performing simulated tibia IMN procedure immediately after training and evaluated by a blinded attending surgeon using procedure-specific checklist and 5-point global assessment scale. Participants returned after 2-weeks for repeat training and evaluation. RESULTS: 20 participants were recruited and randomized into VR (n = 10) and SG (n = 10) groups. All 20 participants completed the first phase and 17 completed the second phase of the study. Aggregate global assessment scores were significantly higher for VR than SG group (17.5 vs. 7.5, p < 0.001), including scores in all individual categories. The percentage of steps completed correctly was significantly higher in the VR group compared to the SG group (63% vs. 25%, p < 0.002). Average improvement between the first and second phases of the study were higher in the VR group compared to SG group across all 5-categories of the global assessment scale, and significantly higher for knowledge of instruments (50% vs. 11%, p, 0.01). DISCUSSION: VR training was more effective than a passive SG in our model of simulated tibia IMN for novice medical students. Virtual reality training may be a useful method to augment orthopedic education.

Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection.

BACKGROUND: Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce. PURPOSE: This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment. STUDY DESIGN/SETTING: Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation. METHODS: Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups. RESULTS: The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56). CONCLUSIONS: Vancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate. CLINICAL SIGNIFICANCE: Vancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma.