Chemokines are increasingly recognised as playing a role in depression. Here we meta-analyse the data on concentrations of all chemokines in patients diagnosed with a major depression versus healthy controls. We included studies which utilised Diagnostic and Statistical Manual (DSM)-IV diagnostic criteria for major depression, participants free from major medical conditions, studies with healthy controls, and unstimulated measurements of chemokines. We only included chemokines which had ≥3 studies performed. Two chemokines and 15 studies in total met criteria for this meta-analysis; 8 for Monocyte Chemotactic Protein (MCP)-1/CCL2 (n=747), and 7 for Interleukin (IL)-8/CXCL8 (n=560). There were significantly higher concentrations of CCL2/MCP-1 in depressed subjects compared with control subjects - overall mean difference of 36.43pg/mL (95% CI: 2.43 to 70.42). There was significant heterogeneity across these studies (I2=98.5%). The estimates of mean difference between the control and depression groups did not remain significant when the trim-and-fill procedure was used to correct for publication bias. There was no significant difference in concentrations of IL-8/CXCL8 in depressed subjects compared with control subjects. Significant heterogeneity was found across these studies (I2=96.7%). The estimates of mean difference between the control and depression groups remained non-significant when the trim-and-fill procedure was used to correct for publication bias. This meta-analysis reports significantly heterogeneity in this field among studies. There are higher concentrations of the chemokine MCP-1/CCL2 in depressed subjects compared with control subjects, and no differences for IL-8/CXCL8. More high quality research and consistent methodologies are needed in this important area of enquiry.

BACKGROUND: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction. PURPOSE: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patients outcome at 6-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx Activity Rating Scale. Patients were followed up at 6 years and asked to complete the identical set of outcome instruments. Regression analysis assessed the meniscal and articular cartilage pathology risk factors for clinical outcomes 6 years after revision ACL reconstruction. RESULTS: An overall 1234 patients were enrolled (716 males, 58%; median age, 26 years). Surgeons reported the pathology at the time of revision surgery in the medial meniscus (45%), lateral meniscus (36%), medial femoral condyle (43%), lateral femoral condyle (29%), medial tibial plateau (11%), lateral tibial plateau (17%), patella (30%), and trochlea (21%). Six-year follow-up was obtained on 79% of the sample (980/1234). Meniscal pathology and articular cartilage pathology (medial femoral condyle, lateral femoral condyle, lateral tibial plateau, trochlea, and patella) were significant drivers of poorer patient-reported outcomes at 6 years (IKDC, KOOS, WOMAC, and Marx). The most consistent factors driving outcomes were having a medial meniscal excision (either before or at the time of revision surgery) and patellofemoral articular cartilage pathology. Six-year Marx activity levels were negatively affected by having either a repair/excision of the medial meniscus (odds ratio range, 1.45-1.72; P≤ .04) or grade 3-4 patellar chondrosis (odds ratio, 1.72; P = .04). Meniscal pathology occurring before the index revision surgery negatively affected scores on all KOOS subscales except for sports/recreation (P < .05). Articular cartilage pathology significantly impaired all KOOS subscale scores (P < .05). Lower baseline outcome scores, higher body mass index, being a smoker, and incurring subsequent surgery all significantly increased the odds of reporting poorer clinical outcomes at 6 years. CONCLUSION: Meniscal and chondral pathology at the time of revision ACL reconstruction has continued significant detrimental effects on patient-reported outcomes at 6 years after revision surgery.

Background

Revision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes than primary ACL reconstruction. The reasons remain varied and not completely understood.

Methods

Patients undergoing revision ACL reconstruction were prospectively enrolled. Data collected included baseline demographics, surgical technique and pathological condition, prescribed rehabilitation instructions, and a series of validated patient-reported outcome instruments. Patients were followed for 2 years and asked to complete a set of outcome instruments identical to those completed at baseline. Subsequent surgical procedures on the ipsilateral knee were recorded. Regression analysis was used to control for age, sex, activity level, baseline outcome scores, and the above-mentioned rehabilitation-related variables in order to assess the factors affecting clinical outcomes 2 years after revision ACL reconstruction.

Results

A total of 843 patients met the inclusion criteria and were successfully enrolled, and 82% (695) were followed for 2 years. Two rehabilitation-related factors were found to influence outcome. First, patients who were prescribed an ACL brace for their return to sports had a significantly better Knee injury and Osteoarthritis Outcome Score (KOOS) for sports and recreational activities at 2 years (odds ratio [OR] =1.50, 95% confidence interval [CI] = 1.07 to 2.11; p = 0.019). Second, patients prescribed an ACL brace for the postoperative rehabilitation period were 2.3 times more likely to have subsequent surgery by 2 years (OR = 2.26, 95% CI = 1.11 to 4.60; p = 0.024). The odds of a graft rerupture were not affected by any type of brace wear.

Conclusions

Rehabilitation-related factors that the physician can control at the time of an ACL reconstruction have the ability to influence clinical outcomes at 2 years. Weight-bearing and motion can be initiated immediately postoperatively. Bracing during the early postoperative period is not helpful. Use of a functional brace early in the postoperative period was associated with an increased risk of a reoperation. Use of a functional brace for a return to sports improved the KOOS on the sports/recreation subscale.

Level of evidence

Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background

Knees undergoing revision anterior cruciate ligament reconstruction (rACLR) have a high prevalence of articular cartilage lesions.

Hypothesis

The prevalence of chondrosis at the time of rACLR is associated with meniscal status and lower extremity alignment.

Study design

Cross-sectional study; Level of evidence, 3.

Methods

Data from the prospective Multicenter ACL Revision Study (MARS) cohort were reviewed to identify patients with preoperative lower extremity alignment films. Lower extremity alignment was defined by the weightbearing line (WBL) as a percentage of the tibial plateau width, while the chondral and meniscal status of each weightbearing compartment was recorded at the time of surgery. Multivariable proportional odds models were constructed and adjusted for relevant factors to examine which risk factors were independently associated with the degree of medial and lateral compartment chondrosis.

Results

The cohort included 246 patients with lower extremity alignment films at the time of rACLR. Mean (±SD) patient age was 26.9 ± 9.5 years and body mass index (BMI) was 26.4 ± 4.6. The medial compartment had more chondrosis (grade 2/3, 42%; grade 4, 6.5%) than did the lateral compartment (grade 2/3, 26%; grade 4, 6.5%). Disruption of the meniscus was noted in 35% of patients on the medial side and 16% in the lateral side. The mean WBL was 0.43 ± 0.13. Medial compartment chondrosis was associated with BMI (P = .025), alignment (P = .002), and medial meniscal status (P = .001). None of the knees with the WBL lateral to 0.625 had grade 4 chondrosis in the medial compartment. Lateral compartment chondrosis was significantly associated with age (P = .013) and lateral meniscal status (P < .001). Subjects with "intact" menisci were found to decrease their odds of having chondrosis by 64% to 84%.

Conclusion

The status of articular cartilage in the tibiofemoral compartments at the time of rACLR is related to meniscal status. Lower extremity alignment and BMI are associated with medial compartment chondrosis.

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.

Background

Lytic or malpositioned tunnels may require bone grafting during revision anterior cruciate ligament reconstruction (rACLR) surgery. Patient characteristics and effects of grafting on outcomes after rACLR are not well described.

Purpose

To describe preoperative characteristics, intraoperative findings, and 2-year outcomes for patients with rACLR undergoing bone grafting procedures compared with patients with rACLR without grafting.

Study design

Cohort study; Level of evidence, 3.

Methods

A total of 1234 patients who underwent rACLR were prospectively enrolled between 2006 and 2011. Baseline revision and 2-year characteristics, surgical technique, pathology, treatment, and patient-reported outcome instruments (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale [Marx]) were collected, as well as subsequent surgery information, if applicable. The chi-square and analysis of variance tests were used to compare group characteristics.

Results

A total of 159 patients (13%) underwent tunnel grafting-64 (5%) patients underwent 1-stage and 95 (8%) underwent 2-stage grafting. Grafting was isolated to the femur in 31 (2.5%) patients, the tibia in 40 (3%) patients, and combined in 88 patients (7%). Baseline KOOS Quality of Life (QoL) and Marx activity scores were significantly lower in the 2-stage group compared with the no bone grafting group (P≤ .001). Patients who required 2-stage grafting had more previous ACLRs (P < .001) and were less likely to have received a bone-patellar tendon-bone or a soft tissue autograft at primary ACLR procedure (P≤ .021) compared with the no bone grafting group. For current rACLR, patients undergoing either 1-stage or 2-stage bone grafting were more likely to receive a bone-patellar tendon-bone allograft (P≤ .008) and less likely to receive a soft tissue autograft (P≤ .003) compared with the no bone grafting group. At 2-year follow-up of 1052 (85%) patients, we found inferior outcomes in the 2-stage bone grafting group (IKDC score = 68; KOOS QoL score = 44; KOOS Sport/Recreation score = 65; and Marx activity score = 3) compared with the no bone grafting group (IKDC score = 77; KOOS QoL score = 63; KOOS Sport/Recreation score = 75; and Marx activity score = 7) (P≤ .01). The 1-stage bone graft group did not significantly differ compared with the no bone grafting group.

Conclusion

Tunnel bone grafting was performed in 13% of our rACLR cohort, with 8% undergoing 2-stage surgery. Patients treated with 2-stage grafting had inferior baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting. Patients treated with 1-stage grafting had similar baseline and 2-year patient-reported outcomes and activity levels compared with patients not undergoing bone grafting.

The underlying theme throughout this series of studies authored by the Multicenter anterior cruciate ligament (ACL) Revision Study consortium has been to determine the modifiable predictors or risk factors of long-term outcomes of revision ACL reconstruction. The observational studies described and summarized in the manuscript are both clinically relevant and of great interest in finding out the long-term consequences of the intervention and its relationship to the original injury. The successful completion of these studies has important implications for both therapy and future clinical trials. The identification of modifiable risk factors will play an important role in secondary prevention, while the identification of nonmodifiable risk factors will aid us in counseling our patients and making surgical decisions. Thus, we expect a profound clinical impact on patients' care. More importantly, this project represents an important step forward in bringing evidence to bear in clinical decision making in orthopedic surgery.

Background

Although graft choice may be limited in the revision setting based on previously used grafts, most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome.

Hypothesis

In the ACL revision setting, there would be no difference between autograft and allograft in rerupture rate and patient-reported outcomes (PROs) at 6-year follow-up.

Study design

Cohort study; Level of evidence, 2.

Methods

Patients who had revision surgery were identified and prospectively enrolled in this cohort study by 83 surgeons over 52 sites. Data collected included baseline characteristics, surgical technique and pathology, and a series of validated PRO measures. Patients were followed up at 6 years and asked to complete the identical set of PRO instruments. Incidence of additional surgery and reoperation because of graft failure were also recorded. Multivariable regression models were used to determine the predictors (risk factors) of PROs, graft rerupture, and reoperation at 6 years after revision surgery.

Results

A total of 1234 patients including 716 (58%) men were enrolled. A total of 325 (26%) underwent revision using a bone-patellar tendon-bone (BTB) autograft; 251 (20%), soft tissue autograft; 289 (23%), BTB allograft; 302 (25%), soft tissue allograft; and 67 (5%), other graft. Questionnaires and telephone follow-up for subsequent surgery information were obtained for 809 (66%) patients, while telephone follow-up was only obtained for an additional 128 patients for the total follow-up on 949 (77%) patients. Graft choice was a significant predictor of 6-year Marx Activity Rating Scale scores (P = .024). Specifically, patients who received a BTB autograft for revision reconstruction had higher activity levels than did patients who received a BTB allograft (odds ratio [OR], 1.92; 95% CI, 1.25-2.94). Graft rerupture was reported in 5.8% (55/949) of patients by their 6-year follow-up: 3.5% (16/455) of patients with autografts and 8.4% (37/441) of patients with allografts. Use of a BTB autograft for revision resulted in patients being 4.2 times less likely to sustain a subsequent graft rupture than if a BTB allograft were utilized (P = .011; 95% CI, 1.56-11.27). No significant differences were found in graft rerupture rates between BTB autograft and soft tissue autografts (P = .87) or between BTB autografts and soft tissue allografts (P = .36). Use of an autograft was found to be a significant predictor of having fewer reoperations within 6 years compared with using an allograft (P = .010; OR, 0.56; 95% CI, 0.36-0.87).

Conclusion

BTB and soft tissue autografts had a decreased risk in graft rerupture compared with BTB allografts. BTB autografts were associated with higher activity level than were BTB allografts at 6 years after revision reconstruction. Surgeons and patients should consider this information when choosing a graft for revision ACL reconstruction.

Background

Osteoarthritis of the knee is commonly diagnosed and monitored with radiography. However, the reliability of radiographic classification systems for osteoarthritis and the correlation of these classifications with the actual degree of confirmed degeneration of the articular cartilage of the tibiofemoral joint have not been adequately studied.

Methods

As the Multicenter ACL (anterior cruciate ligament) Revision Study (MARS) Group, we conducted a multicenter, prospective longitudinal cohort study of patients undergoing revision surgery after anterior cruciate ligament reconstruction. We followed 632 patients who underwent radiographic evaluation of the knee (an anteroposterior weight-bearing radiograph, a posteroanterior weight-bearing radiograph made with the knee in 45° of flexion [Rosenberg radiograph], or both) and arthroscopic evaluation of the articular surfaces. Three blinded examiners independently graded radiographic findings according to six commonly used systems-the Kellgren-Lawrence, International Knee Documentation Committee, Fairbank, Brandt et al., Ahlbäck, and Jäger-Wirth classifications. Interobserver reliability was assessed with use of the intraclass correlation coefficient. The association between radiographic classification and arthroscopic findings of tibiofemoral chondral disease was assessed with use of the Spearman correlation coefficient.

Results

Overall, 45° posteroanterior flexion weight-bearing radiographs had higher interobserver reliability (intraclass correlation coefficient = 0.63; 95% confidence interval, 0.61 to 0.65) compared with anteroposterior radiographs (intraclass correlation coefficient = 0.55; 95% confidence interval, 0.53 to 0.56). Similarly, the 45° posteroanterior flexion weight-bearing radiographs had higher correlation with arthroscopic findings of chondral disease (Spearman rho = 0.36; 95% confidence interval, 0.32 to 0.39) compared with anteroposterior radiographs (Spearman rho = 0.29; 95% confidence interval, 0.26 to 0.32). With respect to standards for the magnitude of the reliability coefficient and correlation coefficient (Spearman rho), the International Knee Documentation Committee classification demonstrated the best combination of good interobserver reliability and medium correlation with arthroscopic findings.

Conclusions

The overall estimates with the six radiographic classification systems demonstrated moderate (anteroposterior radiographs) to good (45° posteroanterior flexion weight-bearing radiographs) interobserver reliability and medium correlation with arthroscopic findings. The International Knee Documentation Committee classification assessed with use of 45° posteroanterior flexion weight-bearing radiographs had the most favorable combination of reliability and correlation.

Level of evidence

Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.