Antibiotic calcium sulphate beads lower the bacterial burden and prevent infection in a mouse model of periprosthetic joint infection.

Aims: Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods: A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. Results: The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. Conclusion: In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.

Similar Medium-Term Revision Rates Following Acute Total Hip Arthroplasty Versus Open Reduction and Internal Fixation for Acetabular Fractures in the Elderly.

BACKGROUND: The management of elderly acetabular fractures is complex, with high rates of conversion total hip arthroplasty (THA) after open reduction and internal fixation (ORIF), but potentially higher rates of complications after acute THA. METHODS: The California Office of Statewide Health Planning and Development database was queried between 2010 and 2017 for all patients aged 60 years or older who sustained a closed, isolated acetabular fracture and underwent ORIF, THA, or a combination. Chi-square tests and Student t tests were used to identify demographic differences between groups. Multivariate regression was used to evaluate predictors of 30-day readmission and 90-day complications. Kaplan-Meier (KM) survival analysis and Cox proportional hazards model were used to estimate the revision surgery-free survival (revision-free survival [RFS]), with revision surgery defined as conversion THA, revision ORIF, or revision THA. RESULTS: A total of 2,184 surgically managed acetabular fractures in elderly patients were identified, with 1,637 (75.0%) undergoing ORIF and 547 (25.0%) undergoing THA with or without ORIF. Median follow-up was 295 days (interquartile range, 13 to 1720 days). 99.4% of revisions following ORIF were for conversion arthroplasty. Unadjusted KM analysis showed no difference in RFS between ORIF and THA (log-rank test P = 0.27). RFS for ORIF patients was 95.1%, 85.8%, 78.3%, and 71.4% at 6, 12, 24 and 60 months, respectively. RFS for THA patients was 91.6%, 88.9%, 87.2%, and 78.8% at 6, 12, 24 and 60 months, respectively. Roughly 50% of revisions occurred within the first year postoperatively (49% for ORIF, 52% for THA). In propensity score-matched analysis, there was no difference between RFS on KM analysis ( P = 0.22). CONCLUSIONS: No difference was observed in medium-term RFS between acute THA and ORIF for elderly acetabular fractures in California. Revision surgeries for either conversion or revision THA were relatively common in both groups, with roughly half of all revisions occurring within the first year postoperatively. LEVEL OF EVIDENCE: III.

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.

Comparison of a 2.7-mm and 3.5-mm locking compression plate for ulnar fractures: a biomechanical evaluation.

Objectives: Implant prominence after ulnar fracture fixation may be mitigated by the use of lower profile plates. The biomechanical strength and stability of 2.7-mm and 3.5-mm locking compression plates for fixation were compared. Methods: Two fracture conditions, transverse (N = 10) and oblique (N = 10), were evaluated in an in vitro study. Half of the specimens for each condition were fixed with 2.7-mm plates and the other half with 3.5-mm plates, all fixed with conventional dynamic compression mechanisms. Specimens were loaded under ±2 Nm of cyclic axial torsion, then under 10 Nm of cyclic cantilever bending, and bending to failure. Interfragmentary motion and strain were analyzed to determine construct stability as a function of fracture pattern and plate size. Results: Interfragmentary motion was significantly larger in all constructs fixed with 2.7-mm plates, compared with 3.5-mm plates (P < 0.01). The 2.7-mm constructs with transverse fractures had the greatest motion, ranging between 5° and 10° under axial rotation and 5.0-6.0 mm under bending. Motions were the lowest for 3.5-mm constructs with oblique fractures, ranging between 3.2 and 4.2 mm under bending and 2°-3.5° for axial rotation. For oblique fractures, the bending moment at ultimate failure was 31.4 ± 3.6 Nm for the 2.7-mm constructs and 10.0 ± 1.9 Nm for 3.5-mm constructs (P < 0.01). Similarly, for transverse fractures, the bending moment was 17.9 ± 4.0 Nm for the 2.7-mm constructs and 9.7 ± 1.3 Nm for the 3.5-mm constructs (P < 0.01). Conclusions: Although 3.5-mm plates were more effective at reducing fracture motion, they were consistently associated with refracture at the distal-most screw hole under load to failure. By contrast, 2.7-mm plates plastically deformed despite excessive loads, potentially avoiding a subsequent fracture. Level of Evidence: Level V.

Higher Rates of Readmission After Acute Total Hip Arthroplasty Versus Open Reduction Internal Fixation for Elderly Acetabular Fractures, a National Study From 2010 to 2019.

OBJECTIVES: To evaluate the initial complications and short-term readmissions and reoperations after open reduction internal fixation (ORIF) versus acute total hip arthroplasty (THA) for elderly acetabular fractures. DESIGN: Retrospective database review. SETTING: All hospitalizations in the National Readmissions Database and National Inpatient Sample. PATIENTS/PARTICIPANTS: Patients 60 years of age or older with closed acetabular fractures managed surgically identified from the National Readmissions Database or National Inpatient Sample between 2010 and 2019. INTERVENTION: Acute THA with or without ORIF. MAIN OUTCOME MEASUREMENTS: 30-, 90-, and 180-day readmissions and reoperations and index hospitalization complications. RESULTS: An estimated 12,538 surgically managed acetabular fractures in elderly patients occurred nationally between 2010 and 2019, with 10,008 (79.8%) undergoing ORIF and 2529 (20.2%) undergoing THA. Length of stay was 1.7 days shorter ( P < 0.001) and probability of nonhome discharge was reduced (OR 0.68, P = 0.009) for THA patients than for ORIF patients. THA was associated with lower rates of pneumonia (4.6 vs. 9.1%, P < 0.001) and other respiratory complications (10.2 vs. 17.6%) when compared with ORIF. At 30 days, THA patients had higher rates of readmission (13.9 vs. 10.1%, P = 0.007), related readmission (5.4 vs. 1.2%, P < 0.001), readmission for dislocation (3.1 vs. 0.3%, P < 0.001), and reoperations (2.9 vs. 0.9%, P = 0.002). At 180 days, THA patients had higher rates of related readmission (10.1% vs. 3.9%, P < 0.001), readmission for dislocation (5.1% vs. 1.3%, P < 0.001), and readmission for SSI (3.4 vs. 0.8%, P = 0.005). CONCLUSIONS: Acute THA is associated with lower length of stay and certain index hospitalization complications, but higher rates of readmissions for related reasons and specifically for dislocation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Increasing Rate of Shoulder Arthroplasty for Geriatric Proximal Humerus Fractures in the United States, 2010-2019.

Introduction: The two historically dominant surgical options for displaced geriatric proximal humerus (PHFx) fractures are open reduction internal fixation (ORIF) and hemiarthroplasty (HA). However, shoulder arthroplasty (SA), predominantly in the form of reverse total shoulder arthroplasty (RTSA), has emerged as an attractive treatment option. We aim to compare the utilization trends, complications, and costs associated with surgical management of geriatric proximal humerus fractures (PHFs) between 2010 and 2019. We hypothesized that 1) the proportion of patients undergoing SA would increase over time, 2) the short-term complication rate in patients undergoing SA would decline over time, and 3) hospital related costs would decline for SA patients over time. Patients and Methods: The National Inpatient Sample was queried from 2010 to 2019 to identify all PHFx in patients aged 65 or older that underwent ORIF, SA, or HA. Multivariable regression was used to evaluate differences between fixation methods regarding health care utilization metrics, hospital costs, and index hospital complications. The primary outcome of interest was the method of surgical management utilized in the treatment of geriatric PHFs, and secondary outcomes of interest included hospitalization cost, length of stay (LOS), discharge destination and index hospitalization complications. Results: A total of 105 886 geriatric patients that underwent surgical management of PHFx were identified. While the proportion undergoing ORIF decreased from 59% to 29%, the proportion undergoing SA increased from 9% to 67%. Hospital costs decreased over time for patients treated with SA and increased for those treated with ORIF. Compared to ORIF, SA was associated with higher cost, decreased length of stay, and lower mortality and complication rates. Conclusion: Over the last decade, SA has become the most common surgical treatment modality performed for geriatric PHFx. Index hospital complications are reduced in SA patients compared to ORIF patients, driven largely by a lower rate of blood transfusion. Although costs are decreasing and average length of stay is now lower in SA patients compared to ORIF patients, SA remains associated with higher hospital costs overall.

Navigated and Robot-Assisted Technology in Total Knee Arthroplasty: Do Outcome Differences Achieve Minimal Clinically Important Difference?

BACKGROUND: In total knee arthroplasty (TKA), computer-assisted navigation (N-TKA) and robotic-assisted methods (RA-TKA) are intended to increase precision of mechanical and component alignment. However, the clinical significance of published patient-reported outcome measure (PROM) differences in comparison to conventional TKA (C-TKA) is unknown. METHODS: A systematic review was performed to identify all studies reporting perioperative PROMs for either primary N-TKA or RA-TKA with a C-TKA comparison cohort with a minimum 1-year follow-up. Relative improvements in PROMs for the two cohorts were compared to published minimal clinically important difference (MCID) values. RESULTS: After systematic review, 21 studies (N = 3,214) reporting on N-TKA and eight studies (N = 1,529) reporting on RA-TKA met inclusion criteria. Eighteen of 20 studies (90%) reported improved radiographic outcomes with N-TKA relative to C-TKA; five of five studies reported improved radiographic outcomes with RA-TKA relative to C-TKA. Five of 21 studies (24%) reported statistically significant greater improvements in clinical PROMs for N-TKA relative to C-TKA, whereas only two (10%) achieved clinical significance relative to MCID on a secondary analysis. One of 8 studies (13%) reported statistically significant greater improvements in PROMs for RA-TKA relative to C-TKA, whereas none achieved clinical significance relative to MCID on a secondary analysis. No studies reported a significant difference in revision rates. CONCLUSION: While most studies comparing RA-TKA and N-TKA with C-TKA demonstrate improved radiographic alignment outcomes, a minority of studies reported PROM differences that achieve clinical significance. Future studies should report data and be interpreted in the context of clinical significance to establish patient and surgeon expectations for emerging technologies.

A Critical Analysis of Lateral Versus Central Endpoint in Distal Tibia Nailing: Does It Affect Alignment?

OBJECTIVES: To evaluate the effect of a traditional "center-center" end point for distal tibia nailing in comparison with a lateral-of-center end point on fracture malalignment in a cadaver model. METHODS: Nine matched pairs of human cadaveric lower-extremity specimens were used to model the effect of nail end point on fracture alignment in extra-articular distal tibia fractures. After simulation of the fracture through a standardized osteotomy, 1 member of each pair was fixed with an intramedullary nail using a "center-center" end point, whereas a lateral-of-center end point was used for the other member of the pair. Specimens were stripped of soft tissue, and digital calipers were used to measure fracture translation and gap medially, laterally, anteriorly, and posteriorly. Coronal plane angulation at each fracture was measured on the final mortise image. RESULTS: The average coronal angulation was 7.0 degrees of valgus (with a SD of 4.1) in central-end point specimens versus 0.2 degrees of valgus (SD = 1.5) in lateral-end point specimens ( P < 0.001). Lateral-end point specimens also demonstrated significantly less fracture gap medially (mean 0.2 vs. 3.1 mm for central-end point specimens, P < 0.001), anteriorly (mean 0.1 vs. 1.3 mm, P = 0.003), and posteriorly (mean 0.3 vs. 2.2 mm, P = 0.003). Lateral-end point specimens also showed less lateral translation (mean 0.6 vs. 1.6 mm, P = 0.006). CONCLUSIONS: Lateral-of-center nail end points may help surgeons restore native alignment in extra-articular distal tibia fractures and avoid valgus malalignment.

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.

Utilization trends and outcomes of computer-assisted navigation in spine fusion in the United States.

BACKGROUND CONTEXT: Computer-assisted navigation (CAN) has emerged in spine surgery as an approach to improve patient outcomes. While there is substantial evidence demonstrating improved pedicle screw accuracy in CAN as compared to conventional spinal fusion (CONV), there is limited data regarding clinical outcomes and utilization trends in the United States. PURPOSE: The purpose of this study was to determine the utilization rates of CAN in the United States, identify patient and hospital trends associated with both techniques, and to compare their results. STUDY DESIGN: Retrospective review of national database. PATIENT SAMPLE: Nationwide Inpatient Sample (NIS), United States national database. OUTCOME MEASURES: CAN utilization, mortality, medical complications, neurologic complications, discharge destination, length of hospital stay, cost of hospital stay. METHODS: The NIS database was queried to identify patients undergoing spinal fusion with CAN or CONV. CAN and CONV utilization were tracked by year and anatomic location (cervical, thoracic, lumbar/lumbosacral). Patient demographics, hospital characteristics, index length of stay (LOS), and cost of stay (COS) were compared between the cohorts. After multivariate adjustment, index hospitalization clinical outcomes were compared. RESULTS: A total of 4,275,413 patients underwent spinal fusion surgery during the study period (2004 to 2014). CONV was performed in 98.4% (4,208,068) of cases and CAN was performed in 1.6% (67,345) of cases. The utilization rate of CAN increased from 0.04% in 2004 to 3.3% in 2014. Overall, CAN was performed most commonly in the lumbar/lumbosacral region (70.4%) compared to the cervical (20.4%) or thoracic (9.2%) regions. When normalized to region-specific rates of fusion with any technique, the proportional utilization of CAN was highest in the thoracic spine (2.7%), followed by the lumbar/lumbosacral (2.2%) and cervical (0.9%) regions. CAN utilization was positively correlated with patient factors including increasing age and number of medical comorbidities. Multivariate adjusted clinical outcomes demonstrated that compared to CONV, CAN was associated with a statistically significant decreased risk of mortality (0.28% vs 0.31%, OR=0.67, 95% CI: 0.46-0.97, p=.035) and increased risk of blood transfusions (9.1% vs 6.7%, OR=1.19, 95% CI: 1.02-1.39, p=.032). However, there was no difference in risk of neurologic complications. CAN patients had an increased average LOS (4.44 days vs. 3.97 days, p<.0001) and average COS ($34,669.49 vs $26,784.62, p<.0001) compared to CONV patients. CONCLUSIONS: CAN utilization increased in the United States from 2004-2014. Use of CAN was proportionately higher in the thoracic and lumbar/lumbosacral regions and in older patients with more comorbidities. Given the continued trend towards increased CAN utilization, large-scale studies are needed to determine the impact of this technology on long-term clinical outcomes.

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.

Surgical treatment of metastatic spine disease: an update on national trends and clinical outcomes from 2010 to 2014.

BACKGROUND CONTEXT: Metastatic spine disease (MSD) is becoming more prevalent as medical treatment for cancers advance and extend survival. More MSD patients are treated surgically to maintain neurological function, ambulation, and quality of life. PURPOSE: The purpose of this study was to use a large, nationally representative database to examine the trends, patient outcomes, and health-care resource utilization associated with surgical treatment of MSD. DESIGN: This was an epidemiologic study using national administrative data from the Nationwide Readmissions Database (NRD). PATIENT SAMPLE: All patients in the NRD from 2010 to 2014 who underwent spinal surgery were included in the study. OUTCOME MEASURES: Mortality, blood transfusion, complications, length of stay, cost, and discharge location during index hospitalization as well as hospital readmission and revision surgery within 90-days of surgery were analyzed. METHODS: International Classification of Diseases, Ninth Revision, (ICD-9) codes was used to identify patients of interest within the NRD from 2010 to 2014. Patients were separated into two cohorts - those with MSD and those without. Trends for surgical treatment of MSD were assessed and outcomes measures for both cohorts were analyzed and compared. RESULTS: The number of surgical treatments for MSD increased from 6,007 in 2010 to 7,032 in 2014 (p-trend<.0001) which represented a 17.1% increase. During index hospitalization, MSD patients had an increased risk of mortality (odds ratio [OR]=3.22, 95% confidence interval [CI]: 2.85-3.63, p<.0001), blood transfusion (OR=2.93, 95% CI: 2.66-3.23, p<.0001), any complication (OR=1.24, 95% CI: 1.18-1.31, p<.0001), and discharge to skilled nursing facility (OR=1.51, 95% CI:1.41-1.61, p<.0001). MSD patients had longer average length of stay (13.05 vs. 4.56 days, p<.0001) and cost ($49,421.75 vs. $26,190.37, p<.0001) during index hospitalization. Furthermore, MSD patients had an increased risk of hospital readmission (OR=2.82, 95% CI: 2.68-2.96, p<.0001), readmission for surgical site infection (OR=2.38, 95% CI: 2.20-2.58, p<.0001), and readmission with neurologic deficits (OR=1.62, 95% CI: 1.27-2.06, p<.0001) despite a decreased risk of revision fusion (OR=0.71, 95% CI: 0.53-0.96, p=.026). CONCLUSIONS: The number of MSD patients who undergo surgical treatments is increasing. Not only do these patients have worse outcomes during index hospitalization, but they are also at an increased risk of hospital readmission for surgical site infection and neurologic complications. These findings stress the need for multidisciplinary perioperative treatment plans that mitigate risks and facilitate quick, effective recovery in these unique, at-risk patients.

Current Trends in Orthopaedic Surgery Residency Applications and Match Rates.

BACKGROUND: The current U.S. orthopaedic residency application process is becoming increasingly impersonal in the wake of an increasing number of applications. Through an analysis of orthopaedic surgery residency application statistics, we have highlighted the effect that the number of orthopaedic applications has on match rate, and we have suggested methods for a more personalized application process. METHODS: Data from the Association of American Medical Colleges (AAMC) and the National Resident Matching Program (NRMP) for United States orthopaedic residency applicants from 2008 to 2018 were collected. These data included the average number of applications submitted per applicant, the average number of applications received per program, the total number of residency positions offered in the U.S., the total number of U.S. applicants, and the total number of U.S. applicants who matched to a U.S. orthopaedic surgery residency program. U.S. applicant match rates and the average number of applications received per residency position offered were calculated. Linear regression models were used to determine the rate at which these variables changed over time. RESULTS: The average number of applications submitted by an applicant increased from 46.5 in 2008 to 74.9 in 2018. The average number of applications received per residency position offered increased from 54.1 in 2008 to 85.7 in 2018. The number of U.S. applicants was 740 in 2008 and 849 in 2018. The number of U.S. orthopaedic residency programs only slightly increased from 160 in 2008 to 171 in 2018. The match rate for U.S. medical school applicants has remained stable from 2008 to 2018 at a mean of 76.9% and a standard deviation of 2.3%. CONCLUSIONS: The match rate has remained stable from 2008 to 2018 despite an increase in the number of applications per position. This discrepancy suggests that increasing the number of submitted applications may not correlate with applicant success. We address this discrepancy and suggest methods that can potentially allow for a more targeted orthopaedic application experience.

Articular Cartilage Repair of the Pediatric and Adolescent Knee with Regard to Minimal Clinically Important Difference: A Systematic Review.

OBJECTIVE: To perform a systematic review of clinical outcomes following microfracture (MFX), autologous chondrocyte implantation (ACI), osteochondral allograft transplantation (OCA), and osteochondral autograft transplantation system (OATS) to treat articular cartilage lesions in pediatric and adolescent patients. We sought to compare postoperative improvements for each cartilage repair method to minimal clinically important difference (MCID) thresholds. DESIGN: MEDLINE, Web of Science, Scopus, and Cochrane Library databases were searched for studies reporting MCID-validated outcome scores in a minimum of 5 patients ≤19 years treated for symptomatic knee chondral lesions with minimum 1-year follow-up. One-sample t tests were used to compare mean outcome score improvements to established MCID thresholds. RESULTS: Twelve studies reporting clinical outcomes on a total of 330 patients following cartilage repair were identified. The mean age of patients ranged from 13.7 to 16.7 years and the mean follow-up was 2.2 to 9.6 years. Six studies reported on ACI, 4 studies reported on MFX, 2 studies reported on OATS, and 1 study reported on OCA. ACI (P < 0.001, P = 0.008) and OCA (P < 0.001) showed significant improvement for International Knee Documentation Committee (IKDC) scores with regard to MCID while MFX (P = 0.66) and OATS (P = 0.11) did not. ACI (P < 0.001) and OATS (P = 0.010) both showed significant improvement above MCID thresholds for Lysholm scores. MFX (P = 0.002) showed visual analog scale (VAS) pain score improvement above MCID threshold while ACI (P = 0.037, P = 0.070) was equivocal. CONCLUSIONS: Outcomes data on cartilage repair in the pediatric and adolescent knee are limited. This review demonstrates that all available procedures provide postoperative improvement above published MCID thresholds for at least one reported clinical pain or functional outcome score.

Comparative Effectiveness of Cartilage Repair With Respect to the Minimal Clinically Important Difference.

BACKGROUND: Recent studies demonstrated a 5% increase in cartilage repair procedures annually in the United States. There is currently no consensus regarding a superior technique, nor has there been a comprehensive evaluation of postoperative clinical outcomes with respect to a minimal clinically important difference (MCID). PURPOSE: To determine the proportion of available cartilage repair studies that meet or exceed MCID values for clinical outcomes improvement over short-, mid-, and long-term follow-up. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic review was performed via the Medline, Scopus, and Cochrane Library databases. Available studies were included that investigated clinical outcomes for microfracture (MFX), osteoarticular transfer system (OATS), osteochondral allograft transplantation, and autologous chondrocyte implantation/matrix-induced autologous chondrocyte implantation (ACI/MACI) for the treatment of symptomatic knee chondral defects. Cohorts were combined on the basis of surgical intervention by performing a meta-analysis that utilized inverse-variance weighting in a DerSimonian-Laird random effects model. Weighted mean improvements in International Knee Documentation Committee (IKDC), Lysholm, and visual analog scale for pain (VAS pain) scores were calculated from preoperative to short- (1-4 years), mid- (5-9 years), and long-term (≥10 years) postoperative follow-up. Mean values were compared with established MCID values per 2-tailed 1-sample Student t tests. RESULTS: A total of 89 studies with 3894 unique patients were analyzed after full-text review. MFX met MCID values for all outcome scores at short- and midterm follow-up with the exception of VAS pain in the midterm. OATS met MCID values for all outcome scores at all available time points; however, long-term data were not available for VAS pain. Osteochondral allograft transplantation met MCID values for IKDC at short- and midterm follow-up and for Lysholm at short-term follow-up, although data were not available for other time points or for VAS pain. ACI/MACI met MCID values for all outcome scores (IKDC, Lysholm, and VAS pain) at all time points. CONCLUSION: In the age of informed consent, it is important to critically evaluate the clinical outcomes and durability of cartilage surgery with respect to well-established standards of clinical improvement. MFX failed to maintain VAS pain improvements above MCID thresholds with follow-up from 5 to 9 years. All cartilage repair procedures met MCID values at short- and midterm follow-up for IKDC and Lysholm scores; ACI/MACI and OATS additionally met MCID values in the long term, demonstrating extended maintenance of clinical benefits for patients undergoing these surgical interventions as compared with MFX.

Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats.

BACKGROUND: Achilles tendon rupture is a common injury and the best treatment option remains uncertain between surgical and nonoperative methods. Biologic approaches using multipotent stem cells such as perivascular stem cells pose a possible treatment option, although there is currently a paucity of evidence regarding their clinical therapeutic use. QUESTIONS/PURPOSES: The purpose of this study was to determine whether injected perivascular stem cells (PSCs) would (1) improve histologic signs of tendon healing (such as percent area of collagen); and (2) improve biomechanical properties (peak load or stiffness) in a rat model of Achilles tendon transection. METHODS: Two subtypes of PSCs were derived from human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection and were randomized to receive injection with saline (eight tendons), hydrogel (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in hydrogel (eight tendons) 3 days postoperatively with the left serving as an uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to track cell viability and localization. At 3 weeks, the rats were euthanized, and investigators blinded to treatment group allocation evaluated tendon healing by peak load and stiffness using biomechanical testing and percent area of collagen using histologic analysis with picrosirius red staining. RESULTS: Histologic analysis showed a higher mean percent area collagen for pericytes (30%) and adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a nonparametric statistical analysis yielded no statistical difference. Mechanical testing demonstrated that the pericyte group had a higher peak load than the saline group (41 ± 7 N versus 26 ± 9 N; mean difference 15 N; 95% confidence interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group (41 ± 7 N versus 25 ± 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The pericyte group demonstrated higher stiffness than the hydrogel group (36 ± 12 N/mm versus 17 ± 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005). CONCLUSIONS: Our results suggest that injection of PSCs improves mechanical but not the histologic properties of early Achilles tendon healing. CLINICAL RELEVANCE: This is a preliminary study that provides more insight into the use of adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon rupture. Further experiments to characterize the function of these cells may serve as a pathway to development of minimally invasive intervention aimed at improving nonoperative management while avoiding the complications associated with surgical treatment down the line.

Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor ß-positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff.

BACKGROUND AND HYPOTHESIS: After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor ß (PDGFRß) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRß+ progenitor cells that contribute to fibroadipogenesis of the rotator cuff. METHODS: We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRß+ cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP+ PDGFRß+ PDGFRα+ cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. RESULTS: GFP+ PDGFRß+ PDGFRα+ cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRß+ PDGFRα+ cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRß+ PDGFRα+ cells were highly adipogenic and significantly more fibrogenic than PDGFRß+ PDGFRα- cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRß+ PDGFRα+ cells. CONCLUSION: PDGFRß+ PDGFRα+ cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRß+ PDGFRα+ cells in vitro. Clinically, perioperative PDGFRß+ PDGFRα+ cell inhibition may limit rotator cuff tissue degeneration and, ultimately, improve surgical outcomes for massive rotator cuff tears.

Is Core Needle Biopsy Reliable in Differentiating Between Aggressive Benign and Malignant Radiolucent Bone Tumors?

BACKGROUND: Although there is widespread acceptance of core needle biopsy (CNB) for diagnosing solid tumors, there is reluctance by some clinicians to use CNB for aneurysmal bone cysts (ABCs) as a result of concerns of safety (bleeding, nerve injury, fracture, readmission, or infection) and reliability, particularly to rule out malignant diagnoses like telangiectatic osteosarcoma. This is especially true when CNB tissue is sent from an outside hospital, where the technique used to obtain the tissue may be spurious. QUESTIONS/PURPOSES: (1) Is CNB effective (provided adequate information to indicate appropriate surgical treatment without further open biopsy) as an initial diagnostic test for ABC? (2) Is CNB accurate (pathology consistent with the subsequent definitive surgical pathologic diagnosis) in differentiating between benign lesions such as primary or secondary ABCs and malignant radiolucent lesions such as telangiectatic osteosarcoma? (3) What are the complications of CNB? (4) Is there any difference in the effectiveness or accuracy of CNB performed at outside institutions when compared with a referral center? METHODS: A retrospective study of our musculoskeletal tumor board pathology database (1990-2016) was performed using search criteria "aneurysmal bone cyst" or "telangiectatic osteosarcoma." Only patients undergoing a CNB who proceeded to definitive surgical resection with final pathology were included. Excluding outside CNBs, CNB was performed after presentation at a musculoskeletal tumor board as a result of atypical features on imaging or history concerning for malignancy. Outside CNB tissue was reviewed by our pathologists. If there was sufficient tissue for diagnosis, the patient proceeded to definitive surgery. If not, the patient underwent open biopsy. CNB diagnosis, open biopsy results, and open surgical resection pathology were reviewed. Complications, including bleeding, infection, nerve injury, readmission, or fracture, between the CNB and definitive open surgical procedure (mean 1.6 months) were documented. CNBs were considered "effective" if they yielded pathology considered sufficient to proceed with appropriate definitive surgery without additional open biopsy. CNBs were considered "accurate" if they were effective and yielded a pathologic diagnosis that matched the subsequent definitive surgical pathology. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of obtaining a malignant diagnosis using CNB were also calculated. RESULTS: A total of 81% (59 of 73) of CNBs were effective. Ninety-three percent (55 of 59) of CNBs were classified as accurate. Diagnostic CNBs had a sensitivity and specificity of 89% (eight of nine) and 100% (51 of 51), respectively. The PPV was 1.00 and the NPV was 0.82. There were no complications. With the numbers available, there was no difference in efficacy (90% [37 of 41 versus 14 of 15]; odds ratio, 0.97 [95% confidence interval {CI}, 0.41-2.27], p = 0.94) or accuracy (92% [34 of 37 versus 13 of 14]; odds ratio, 0.87 [95% CI, 0.08-9.16], p = 0.91) between CNBs performed in house and those referred from outside. CONCLUSIONS: These data suggest that CNBs are useful as an initial diagnostic test for ABC and telangiectatic osteosarcoma. Tissue from outside CNBs can be read reliably without repeat biopsy. If confirmed by other institutions, CNB may be considered a reasonable approach to the diagnosis of aggressive, radiolucent lesions of bone. LEVEL OF EVIDENCE: Level III, diagnostic study.

Academic productivity among fellowship associated adult total joint reconstruction surgeons.

BACKGROUND: The Hirsch index (h-index) is a measure that evaluates both research volume and quality-taking into consideration both publications and citations of a single author. No prior work has evaluated academic productivity and contributions to the literature of adult total joint replacement surgeons. This study uses h-index to benchmark the academic impact and identify characteristics associated with productivity of faculty members at joint replacement fellowships. METHODS: Adult reconstruction fellowship programs were obtained via the American Association of Hip and Knee Surgeons website. Via the San Francisco match and program-specific websites, program characteristics (Accreditation Council for Graduate Medical Education approval, academic affiliation, region, number of fellows, fellow research requirement), associated faculty members, and faculty-specific characteristics (gender, academic title, formal fellowship training, years in practice) were obtained. H-index and total faculty publications served as primary outcome measures. Multivariable linear regression determined statistical significance. RESULTS: Sixty-six adult total joint reconstruction fellowship programs were identified: 30% were Accreditation Council for Graduate Medical Education approved and 73% had an academic affiliation. At these institutions, 375 adult reconstruction surgeons were identified; 98.1% were men and 85.3% had formal arthroplasty fellowship training. Average number of publications per faculty member was 50.1 (standard deviation 76.8; range 0-588); mean h-index was 12.8 (standard deviation 13.8; range 0-67). Number of fellows, faculty academic title, years in practice, and formal fellowship training had a significant (P < .05) positive correlation with both h-index and total publications. CONCLUSIONS: The statistical overview presented in this work can help total joint surgeons quantitatively benchmark their academic performance against that of their peers.