Subsequent Surgery After Revision Anterior Cruciate Ligament Reconstruction: Rates and Risk Factors From a Multicenter Cohort

BACKGROUND: While revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR. PURPOSE: To report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation. RESULTS: Of the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate. CONCLUSION: There was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Relationship Between Sports Participation After Revision Anterior Cruciate Ligament Reconstruction and 2-Year Patient-Reported Outcome Measures

BackgroundAnterior cruciate ligament (ACL) revision cohorts continually report lower outcome scores on validated knee questionnaires than primary ACL cohorts at similar time points after surgery. It is unclear how these outcomes are associated with physical activity after physician clearance for return to recreational or competitive sports after ACL revision surgery.HypothesesParticipants who return to either multiple sports or a singular sport after revision ACL surgery will report decreased knee symptoms, increased activity level, and improved knee function as measured by validated patient-reported outcome measures (PROMs) and compared with no sports participation. Multisport participation as compared with singular sport participation will result in similar increased PROMs and activity level.Study designCross-sectional study; Level of evidence, 3.MethodsA total of 1205 patients who underwent revision ACL reconstruction were enrolled by 83 surgeons at 52 clinical sites. At the time of revision, baseline data collected included the following: demographics, surgical characteristics, previous knee treatment and PROMs, the International Knee Documentation Committee (IKDC) questionnaire, Marx activity score, Knee injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A series of multivariate regression models were used to evaluate the association of IKDC, KOOS, WOMAC, and Marx Activity Rating Scale scores at 2 years after revision surgery by sports participation category, controlling for known significant covariates.ResultsTwo-year follow-up was obtained on 82% (986 of 1205) of the original cohort. Patients who reported not participating in sports after revision surgery had lower median PROMs both at baseline and at 2 years as compared with patients who participated in either a single sport or multiple sports. Significant differences were found in the change of scores among groups on the IKDC (P &lt; .0001), KOOS-Symptoms (P = .01), KOOS-Sports and Recreation (P = .04), and KOOS-Quality of Life (P &lt; .0001). Patients with no sports participation were 2.0 to 5.7 times more likely than multiple-sport participants to report significantly lower PROMs, depending on the specific outcome measure assessed, and 1.8 to 3.8 times more likely than single-sport participants (except for WOMAC-Stiffness, P = .18), after controlling for known covariates.ConclusionParticipation in either a single sport or multiple sports in the 2 years after ACL revision surgery was found to be significantly associated with higher PROMs across multiple validated self-reported assessment tools. During follow-up appointments, surgeons should continue to expect that patients who report returning to physical activity after surgery will self-report better functional outcomes, regardless of baseline activity levels