Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma.

This study aims to investigate whether adding neoadjuvant radiotherapy (RT), anti-programmed cell death protein-1 (PD-1) antibody (anti-PD-1), or RT + anti-PD-1 to surgical resection improves disease-free survival for mice with soft tissue sarcomas (STS). We generated a high mutational load primary mouse model of STS by intramuscular injection of adenovirus expressing Cas9 and guide RNA targeting Trp53 and intramuscular injection of 3-methylcholanthrene (MCA) into the gastrocnemius muscle of wild-type mice (p53/MCA model). We randomized tumor-bearing mice to receive isotype control or anti-PD-1 antibody with or without radiotherapy (20 Gy), followed by hind limb amputation. We used micro-CT to detect lung metastases with high spatial resolution, which was confirmed by histology. We investigated whether sarcoma metastasis was regulated by immunosurveillance by lymphocytes or tumor cell-intrinsic mechanisms. Compared with surgery with isotype control antibody, the combination of anti-PD-1, radiotherapy, and surgery improved local recurrence-free survival (P = 0.035) and disease-free survival (P = 0.005), but not metastasis-free survival. Mice treated with radiotherapy, but not anti-PD-1, showed significantly improved local recurrence-free survival and metastasis-free survival over surgery alone (P = 0.043 and P = 0.007, respectively). The overall metastasis rate was low (∼12%) in the p53/MCA sarcoma model, which limited the power to detect further improvement in metastasis-free survival with addition of anti-PD-1 therapy. Tail vein injections of sarcoma cells into immunocompetent mice suggested that impaired metastasis was due to inability of sarcoma cells to grow in the lungs rather than a consequence of immunosurveillance. In conclusion, neoadjuvant radiotherapy improves metastasis-free survival after surgery in a primary model of STS.

Imageless Computer Navigation Reduces 5-Year All-Cause Revision Rates After Primary Total Knee Arthroplasty.

BACKGROUND: The use of surgical navigation has been shown to reduce revision rates after total knee arthroplasty (TKA) in patients <65 years of age. It is unknown if this benefit extends to older patients. We hypothesized that the use of surgical navigation would reduce rates of all-cause revision in patients of all ages. METHODS: In this cohort study, we queried the Truven MarketScan all-payer database to identify patients who underwent TKA from 2007 to 2015. Current Procedural Terminology codes were used to create 2 groups based on whether intraoperative navigation was used. Demographics, comorbidities, complications, and revision rates were determined. International Classification of Diseases codes were used to determine reasons for revision. RESULTS: The conventional TKA cohort included 312,173 patients. The navigation cohort included 20,881 patients. There were not any clinically significant differences in demographics between the cohorts. All-cause revision rates were lower in the navigation cohort at 1 year (0.4% vs 0.5%, P = .04), 2 years (0.7% vs 0.9%, P = .003), and 5 years (0.9% vs 1.3%, P < .001) of follow-up. Revisions for mechanical loosening were more common in the conventional cohort (30.8% vs 21.9%, P = .009). Rates of revision for other causes, including infection, did not differ between groups, with the numbers available. CONCLUSION: The use of surgical navigation yielded a 30.7% reduction in the all-cause revision rate at 5-year follow-up compared to conventional TKA. This benefit increased as follow-up duration increased. Increased usage of this inexpensive technology, from the current 6.3% in this US cohort, may reduce healthcare costs. LEVEL OF EVIDENCE: III.

Revision Total Joint Arthroplasty: Final Stop Tertiary Referral Center.

High complication rates associated with revision total knee arthroplasty (TKA) and total hip arthroplasty (THA) may unequally burden tertiary referral centers, which manage medically complex patients. The authors aimed to quantify TKA and THA referral patterns at a tertiary referral center based on travel distance and patient comorbidities. All patients who underwent primary or revision TKA or THA at the investigating institution from 2012 to 2016 were identified. Travel distance was calculated using each patient's home address and stratified into less than 25 miles, 25 to 74 miles, and 75 miles or more. Age, body mass index, Charlson Comorbidity Index, and postoperative clinical data were identified. Patients were analyzed based on procedure performed and travel distance. A total of 4245 procedures were included for analysis (1754 primary TKAs, 432 revision TKAs, 1503 primary THAs, and 556 revision THAs). Patients living 75 miles or more away had significantly higher odds of undergoing revision arthroplasty compared with patients living within 25 miles (knee: odds ratio [OR], 2.43; hip: OR, 2.61; P<.001). Charlson Comorbidity Index did not increase with travel distance. Patients traveling 75 miles or more were more likely to have periprosthetic fracture (OR, 3.91; P=.011) and less likely to have dislocation (OR, 0.54; P=.026) as the surgical indication for revision. Patients referred to a tertiary center were more likely to necessitate revision total joint arthroplasty but did not differ in comorbidity profile compared with local patients. Periprosthetic fracture, a particularly high-risk surgical indication, was overrepresented among referral patients. These data suggest that factors such as underlying diagnosis, but not preoperative medical comorbidities, may influence referral patterns. [Orthopedics. 2021;44(4):e477-e481.].

Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy.

Immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Most preclinical immunotherapy studies utilize transplant tumor models, which overestimate patient responses. Here, we show that transplant sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous sarcomas, which demonstrate immunoediting, decreased neoantigen expression, and tumor-specific immune tolerance. We characterize tumor-infiltrating immune cells from transplant and primary tumors, revealing striking differences in their immune landscapes. Although radiotherapy remodels myeloid cells in both models, only transplant tumors are enriched for activated CD8+ T cells. The immune microenvironment of primary murine sarcomas resembles most human sarcomas, while transplant sarcomas resemble the most inflamed human sarcomas. These results identify distinct microenvironments in murine sarcomas that coevolve with the immune system and suggest that patients with a sarcoma immune phenotype similar to transplant tumors may benefit most from PD-1 blockade and radiotherapy.

Patient Risk Profile for Unplanned 90-Day Emergency Department Visits Differs Between Total Hip and Total Knee Arthroplasty.

Numerous studies have explored 90-day readmissions following total joint arthroplasty; however, there is a paucity of literature concerning 90-day emergency department (ED) visits. The authors aimed to characterize the risk factors for ED presentations and to determine the primary reasons for return, hypothesizing that certain medical comorbidities would account for resource utilization. The institutional database was queried for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients were stratified based on return visits to the ED within 90 days postoperatively. Univariable and multivariable analyses were performed to determine the factors most predictive of ED return for each THA and TKA. A total of 10,479 procedures resulted in 1234 90-day ED visits made by 937 patients. Significant predictors of 90-day ED return after THA included black race, age older than 80 years, congestive heart failure, valvular heart disease, metastatic disease, peripheral vascular disease, alcoholism, drug use, depression, and discharge to a skilled nursing facility. In contrast, only black race, liver insufficiency, cancer, and pulmonary hypertension were predictive of ED return following TKA. The primary risk factors for ED return differ for THA and TKA, and this is not currently reflected in the medical severity diagnosis-related group system. Specifically, black patients with multiple comorbidities are at high risk for unplanned ED visits following THA. This should be considered in patient counseling and outreach programs when attempting to mitigate the postoperative risks and to decrease 90-day resource utilization in this patient population. [Orthopedics. 2020;43(5):295-302.].

Implementation of a Surgical Oncology Disparities Curriculum for Preclinical Medical Students.

BACKGROUND: Underinsured and uninsured surgical-oncology patients are at higher risk of perioperative morbidity and mortality. Curricular innovation is needed to train medical students to work with this vulnerable population. We describe the implementation of and early educational outcomes from a student-initiated pilot program aimed at improving medical student insight into health disparities in surgery. MATERIALS/METHODS: First-year medical students participated in a dual didactic and perioperative-liaison experience over a 10-month period. Didactic sessions included surgical-skills training and faculty-led lectures on financial toxicity and management of surgical-oncology patients. Students were partnered with uninsured and Medicaid patients receiving surgical-oncology care and worked with these patients by providing appointment reminders, clarifying perioperative instructions, and accompanying patients to surgery and clinic appointments. Students' interest in surgery and self-reported comfort in 15 Association of American Medical Colleges core competencies were assessed with preparticipation and postparticipation surveys using a 5-point Likert scale. RESULTS: Twenty-four first-year students were paired with 14 surgical-oncology patients during the 2017-2018 academic year. Sixteen students (66.7%) completed both preprogram and postprogram surveys. Five students (31.3%) became "More Interested" in surgery, whereas 11 (68.8%) reported "Similar Interest or No Change." Half of the students (n = 8) felt more prepared for their surgery clerkship after participating. Median self-reported comfort improved in 7/15 competencies including Oral Communication and Ethical Responsibility. All students reported being "Somewhat" or "Extremely Satisfied" with the program. CONCLUSIONS: We demonstrate that an innovative program to expose preclinical medical students to challenges faced by financially and socially vulnerable surgical-oncology patients is feasible and may increase students' clinical preparedness and interest in surgery.

Extended Oral Antibiotics and Infection Prophylaxis after a Primary or Revision Total Knee Arthroplasty.

One of the most common reasons for failure of primary total knee arthroplasty and need for revision surgery is periprosthetic infection. Antibiotics are one of the mainstays of treatment to address prosthetic joint infections, but the route of administration and timing of delivery to optimize patient outcomes are debated. This article reviews the use and attributes of commonly used oral antibiotics, especially extended or long-term utilization, as prophylaxis and treatment for prosthetic joint infections in a primary or revision total knee arthroplasty, which include debridement, antibiotics, and implant retention, one-stage and two-stage exchange arthroplasty.

Incidence of Periprosthetic Femur Fractures Utilizing the Posterior Approach with a Single Wedge Tapered Stem.

We sought to determine early periprosthetic femur fracture rate and stem-related failures in primary total hip arthroplasty (THA) performed through a posterior approach with a cementless wedge stem. We reviewed 818 primary THAs in 713 patients with a single wedge tapered titanium component. We used multivariate logistic regression to determine predisposing factors to stem failure. The mean radiographic follow up was 1.6 years. Overall there were eight perioperative femur fractures (0.98%). There were two intraoperative fractures (0.24%), six postoperative fractures (0.73%) and one case of stem subsidence (0.1%). There was a 0.49% rate of operative fractures occurring within 90 days of surgery. There were five stem revisions due to loosening or fracture (0.61%). When excluding infection, the ultimate stem retention rate at latest follow up was 99.3%. Multivariate logistic regression did not find age, sex, body mass index or American Society of Anesthesiologists (ASA) score significantly associated with periprosthetic fracture. (Journal of Surgical Orthopaedic Advances 28(4):277-280, 2019).

Neutrophils promote tumor resistance to radiation therapy.

Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies, including locally advanced cervical cancer, head and neck cancer, and lung cancer. The addition of concurrent platinum-based radiosensitizing chemotherapy improves local control and patient survival. Enhanced outcomes with concurrent chemoradiotherapy may result from increased direct killing of tumor cells and effects on nontumor cell populations. Many patients treated with concurrent chemoradiotherapy exhibit a decline in neutrophil count, but the effects of neutrophils on radiation therapy are controversial. To investigate the clinical significance of neutrophils in the response to RT, we examined patient outcomes and circulating neutrophil counts in cervical cancer patients treated with definitive chemoradiation. Although pretreatment neutrophil count did not correlate with outcome, lower absolute neutrophil count after starting concurrent chemoradiotherapy was associated with higher rates of local control, metastasis-free survival, and overall survival. To define the role of neutrophils in tumor response to RT, we used genetic and pharmacological approaches to deplete neutrophils in an autochthonous mouse model of soft tissue sarcoma. Neutrophil depletion prior to image-guided focal irradiation improved tumor response to RT. Our results indicate that neutrophils promote resistance to radiation therapy. The efficacy of chemoradiotherapy may depend on the impact of treatment on peripheral neutrophil count, which has the potential to serve as an inexpensive and widely available biomarker.

Predicting Success of Two-Stage Exchange for Prosthetic Joint Infection Using C-Reactive Protein/Albumin Ratio.

Two-stage exchange is most commonly used for treatment of prosthetic joint infections (PJI) but, this may fail to eradicate infections. C-reactive protein/albumin ratio (CAR) has been used to predict survival and operative success in other surgical subspecialties and so, we assess the association between CAR and reimplantation success during two-stage revision for PJI defined by the Musculoskeletal Infection Society following a primary total hip (THA) or knee (TKA) arthroplasty. From January, 2005 to December, 2015, two institutional databases were queried and patient demographics, antibiotic duration, C-reactive protein, and albumin were collected prior to reimplantation. Two-stage revisions were considered successful if patients were off of antibiotics and did not require a repeat surgery. CAR was available for 79 patients (34 hips and 46 knees) with 61 successful two-stage revisions and 18 failures. The average CAR for patients with successful reimplantation was 1.2 (0.2, 3.0) compared to 1.0 (0.4, 3.2) for treatment failure. However, this was not statistically significant (p=0.766). Therefore, CAR is not applicable in predicting the prognosis of two-stage revisions for PJI in total arthroplasty but other preoperative inflammatory-based prognostic scores should be explored.

Transient osteoporosis of the hip after bariatric surgery.

Transient osteoporosis is a rare manifestation of acute hip pain which typically resolves with weight-bearing restrictions and pain management. Our case report presents a patient who experienced atraumatic right hip pain a few weeks after an uncomplicated bariatric surgery and was diagnosed with transient osteoporosis of the hip. Her condition resolved after weeks of protected weight-bearing restrictions and nonsteroidal anti-inflammatories. Transient osteoporosis should be considered in the differential diagnosis of hip pain in patients who have undergone previous bariatric surgery.

Conversion Total Knee Arthroplasty: A Distinct Surgical Procedure With Increased Resource Utilization.

BACKGROUND: Current Procedural Terminology coding currently makes no distinction between primary total knee arthroplasty (TKA) and conversion TKA, in which periarticular hardware components must be removed prior to or during TKA. We hypothesize that conversion TKA will carry increased operative time, blood loss, postoperative complications, and 90-day emergency department/readmission rate compared to primary TKA. METHODS: Patients undergoing conversion TKA from 2005 to 2017 were identified from an institutional database and matched to primary TKA patients by age, gender, American Society of Anesthesiologists score, body mass index, and procedure date (±1 year). Intraoperative data and 90-day postoperative complications were compared between groups. RESULTS: One hundred nine conversion TKA patients with periarticular hardware were removed prior to (n = 51) or during (n = 58) TKA and 109 primary TKA control patients were included. Conversion TKA was associated with increased tourniquet time (91 vs 71 minutes, P < .001), operative time (147 vs 113 minutes, P < .001), blood loss (225 vs 176 mL, P = .010), 90-day readmissions (14.6% vs 4.2%, P = .020), wound complication (5.6% vs 0.0%, P = .025), periprosthetic joint infection (7.9% vs 0.0%, P = .005), irrigation/debridement (9.0% vs 1.1%, P = .016), and a trend toward increased mechanical complication (6.7% vs 1.1%, P = .058). Timing of hardware removal did not affect intraoperative or postoperative outcomes. CONCLUSION: Conversion TKA is associated with higher operative time, blood loss, readmission rate, and postoperative complications compared to primary TKA. Without a proper billing code and appropriate reimbursement level to match the expected operative and postacute resource utilization by these cases, physicians may be disincentivized to perform these operations.

Predicting Inpatient Dissatisfaction Following Total Joint Arthroplasty: An Analysis of 3,593 Hospital Consumer Assessment of Healthcare Providers and Systems Survey Responses.

BACKGROUND: The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, created by the Centers for Medicare and Medicaid, is directly tied to hospital reimbursement. The purpose of this study is to identify factors that are predictive HCAHPS survey responses following primary hip and knee arthroplasty. METHODS: Prospectively collected HCAHPS responses from patients undergoing elective hip and knee arthroplasty between January 2013 and October 2017 at our institution were analyzed. Patient age, gender, race, marital status, body mass index, American Society of Anesthesiologists score, preoperative pain score, smoking status, alcohol use, illegal drug use, socioeconomic quartile, insurance type, procedure type, hospital type (academic vs community), distance to medical center, length of stay (LOS), and discharge disposition were obtained and correlated with HCAHPS inpatient satisfaction scores. RESULTS: Responses from 3593 patients were obtained: 1546 total hip arthroplasties, 1899 total knee arthroplasties, and 148 unicompartmental knee arthroplasties. Mean overall HCAHPS score was 79.2. Women had lower inpatient satisfaction than men (77.6 vs 81.6, P < .001). Alcohol consumers had lower inpatient satisfaction than abstainers (77.7 vs 81.6, P < .001). Inpatient satisfaction varied by socioeconomic quartile (P < .001) with patients in the highest quartile having lower satisfaction than patients in all other quartiles (P < .001). Patients discharged to a facility had lower inpatient satisfaction than those discharged home (71.2 vs 80.2, P < .001). An inverse correlation between inpatient satisfaction and LOS (r = -0.19, P < .001) and a direct correlation between satisfaction and distance to medical center (r = 0.06, P < .001) were seen. CONCLUSION: Patients more likely to report lower levels of inpatient satisfaction after total joint arthroplasty are female, affluent, and alcohol consumers, who are discharged to postacute care facilities. Inpatient satisfaction was inversely correlated with LOS and positively correlated with distance from patient home to medical center. These findings provide targets for improvements in TJA inpatient care.