Citations

Background: Numerous large-scale studies have found diverse risk factors for Parkinson’s disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD). In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. Objective: To define risk factors for PD in patients with or without associated RBD. Methods: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. Results: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05–9.223), and to have been regular smokers (OR = 1.96 (1.04–3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07–10.0). Conclusion: The RBD-specific subtype of PD may also have a different risk factor profile.

AbstractIntroductionThe genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain.MethodsWe genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome‐wide association study.ResultsWe confirm that variation in/near APOE/TOMM40 (P = 6 × 10−14) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, P = .0007). We found evidence for risk in/near CR1 (P = 7 × 10−4), ABCA7 (P = .02) and BIN1 (P = .04). ORs at variants near INPP5D and NME8 did not overlap between PCA and typical AD. Exploratory genome‐wide association studies confirmed APOE and identified three novel loci: rs76854344 near CNTNAP5 (P = 8 × 10−10 OR = 1.9 [1.5–2.3]); rs72907046 near FAM46A (P = 1 × 10−9 OR = 3.2 [2.1–4.9]); and rs2525776 near SEMA3C (P = 1 × 10−8, OR = 3.3 [2.1–5.1]).DiscussionWe provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD.

Background: Reconstruction of anterior cruciate ligament (ACL) tears may potentially prevent the development of secondary meniscal injuries and arthritis. Purpose/Hypothesis: The purpose of this study was to (1) evaluate the protective benefit of ACL reconstruction (ACLR) in preventing subsequent meniscal tears or arthritis, (2) determine if earlier ACLR (<1 year after injury) offers greater protective benefits than delayed reconstruction (≥1 year after injury), and (3) evaluate factors predictive of long-term sequelae after ACLR. The hypothesis was that the incidence of secondary meniscal tears, arthritis, and total knee arthroplasty (TKA) would be higher in patients treated nonoperatively after ACL tears than patients treated with surgical reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective study included a population-based incidence cohort of 964 patients with new-onset, isolated ACL tears between 1990 and 2000 as well as an age- and sex-matched cohort of 964 patients without ACL tears. A chart review was performed to collect information related to the initial injury, treatment, and outcomes. A total of 509 patients were treated with early ACLR, 91 with delayed ACLR, and 364 nonoperatively. All patients were retrospectively followed (range, 2 months to 25 years) to determine the development of subsequent meniscal tears, arthritis, or TKA. Results: At a mean follow-up of 13.7 years, patients treated nonoperatively after ACL tears had a significantly higher likelihood of developing a secondary meniscal tear (hazard ratio [HR], 5.4; 95% CI, 3.8-7.6), being diagnosed with arthritis (HR, 6.0; 95% CI, 4.3-8.4), and undergoing TKA (HR, 16.7; 95% CI, 5.0-55.2) compared with patients treated with ACLR. Similarly, patients treated with delayed ACLR had a higher likelihood of developing a secondary meniscal tear (HR, 3.9; 95% CI, 2.2-6.9) and being diagnosed with arthritis (HR, 6.2; 95% CI, 3.4-11.4) compared with patients treated with early ACLR. Age >21 years at the time of injury, articular cartilage damage, and medial/lateral meniscal tears were predictive of arthritis after ACLR. Conclusion: Patients treated with ACLR have a significantly lower risk of secondary meniscal tears, symptomatic arthritis, and TKA when compared with patients treated nonoperatively after ACL tears. Similarly, early ACLR significantly reduces the risk of subsequent meniscal tears and arthritis compared with delayed ACLR.

Objective Autologous chondrocyte implantation (ACI) has not been proven to be durable over the long-term. The purpose of this systematic review was (1) to evaluate activity level and knee function, (2) to evaluate reoperation and failure rates, and (3) to analyze risk factors for reoperation and failure of ACI at minimum long-term follow-up. Design A comprehensive review was performed for studies with long-term outcomes after ACI for cartilage defect repair. Studies reported outcome scores such as Tegner score, Lysholm score, and International Knee Documentation Society (IKDC) score along with rates of failure and reoperation. Modified Coleman Methodology Scores were calculated to assess study methodological quality. Results Nine studies with a total of 771 patients with a mean age of 33.4 ± 2.5 years, mean defect size of 5.9 ± 1.6 cm 2 , and mean follow-up of 11.4 years were included. Tegner score, Lysholm score, and IKDC score change from preoperative to final follow-up was 1.1 (95% CI 0.8-1.4, P < 0.001), 24.9 points (95% CI 18.8-31, P < 0.001), and 16.5 points (95% CI 5.4-27.5, P < 0.01), respectively. The mean failure and reoperation rates were 18% and 37%, respectively. Increased age and lesion size (>4.5 cm 2 ) were significantly correlated with increased risk of reoperation and failure. Conclusions Overall, ACI demonstrated successful outcomes in 82% of patients over the long-term. Increased patient age and lesion size greater than 4.5 cm 2 were risk factors for a higher reoperation and failure rate. Nonetheless, this review is limited by heterogeneity in surgical technique, and lesion and patient characteristics.

Background: Among patients treated nonoperatively for 1 year after anterior cruciate ligament (ACL) disruption, little is known about the frequency of ACL reconstruction within the first year of injury and the effect of age range, sex, and meniscal tears on the incidence of ACL reconstruction between 1 and 10 years after injury. Purpose: To (1) define the rate of delayed ACL reconstruction (between 1 and 10 years after injury) in a population-based cohort of isolated ACL tears and (2) evaluate predictive factors associated with delayed reconstruction. Study Design: Case-control study; Level of evidence, 3. Methods: The study included a population-based cohort of 1841 patients with new-onset, isolated ACL tears that occurred between January 1, 1990, and December 31, 2010. The complete medical records were reviewed to confirm diagnosis and collect data on clinical characteristics and details of subsequent ACL surgery. To evaluate the incidence of ACL reconstruction between 1 and 10 years after injury, landmark survival analysis was performed with a landmark set at 1 year after injury. Early and late predictors of ACL reconstruction were analyzed using Cox proportional hazards regression. Results: A total of 661 patients were treated nonoperatively for the first year after ACL tears. Over a mean 10 years of follow-up, 213 patients (32%) underwent ACL reconstruction between 1 and 10 years after injury. Young age (hazard ratio [HR], 0.55 per decade increase in age; 95% CI, 0.48-0.62) and meniscal tear at injury (HR, 1.48; 95% CI, 1.12-1.95) were significant predictors of undergoing delayed reconstruction. The rate of delayed ACL reconstruction decreased significantly over the study period ( P < .03). There was no association between sex (HR, 0.89; 95% CI, 0.67-1.16) and delayed ACL reconstruction. Among patients who had delayed ACL reconstruction, 40% experienced a secondary meniscal tear before surgery. Conclusion: In this study population of 1841 patients, 62% of patients received ACL reconstruction within 1 year of injury. Of patients treated nonoperatively for 1 year after ACL tears, 32% underwent delayed ACL reconstruction. Predictors of reconstruction beyond 1 year were young age (50% reduction in reconstruction per decade increased age) and baseline meniscal tear. Sex was not predictive for reconstruction beyond 1 year from injury.

Background: The incidence of isolated anterior cruciate ligament (ACL) tears in the general population is not well defined. Purpose/Hypothesis: The purpose of this study was to define the population-based incidence of ACL tears, describe trends in ACL injuries over time, and evaluate changes in the rate of surgical management. The hypothesis was that the incidence of ACL injury and the rate of subsequent ACL reconstruction increase over time. Study Design: Cohort study; Level of evidence, 3. Methods: The study population included 1841 individuals who were diagnosed with new-onset, isolated ACL tears (without concomitant ligament injury that required surgery) between January 1, 1990, and December 31, 2010. The complete medical records were reviewed to confirm diagnosis and to extract injury and treatment details. Age- and sex-specific incidence rates were calculated and adjusted to the 2010 US population. Poisson regression analyses were performed to examine incidence trends by age, sex, and calendar period. Results: The overall age- and sex-adjusted annual incidence of ACL tears was 68.6 per 100,000 person-years. Incidence was significantly higher in male patients than in females (81.7 vs 55.3 per 100,000, P < .001). The incidence of isolated ACL tears decreased significantly over time in males ( P < .001) but remained relatively stable in females. Age-specific patterns differed in male and female patients, with a peak in incidence (241.0 per 100,000) between 19 and 25 years in males and a peak in incidence (227.6 per 100,000) between 14 and 18 years in females. The rate of ACL reconstruction increased significantly over time in all age groups ( P < .001). Conclusion: With an annual incidence of 68.6 per 100,000 person-years, isolated ACL tears remain a common orthopaedic injury. Differences in age-specific incidence trends in male and female patients may potentially reflect differences in sports participation patterns through the high school and college years. The significant increase in the rate of ACL reconstruction over time may reflect changing surgical indications or an increasing desire among patients to return to high levels of activity after ACL injury.

ABSTRACTPreservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA‐seq) and real‐time reverse transcription quantitative polymerase chain reaction (RT‐qPCR) to assess genome‐wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM‐related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950–1959, 2016.

Purpose To evaluate (1) activity level and knee function, (2) reoperation and failure rates, and (3) risk factors for reoperation and failure of osteochondral autograft transfer (OAT) at minimum long‐term follow‐up. Methods A comprehensive review was performed for long‐term outcomes after OAT. Studies reported on activity‐based outcomes (Tegner Activity Scale) and clinical outcomes (Lysholm score and International Knee Documentation Committee score). Reoperation and failure rates, as defined by the publishing authors, were recorded for each study. Modified Coleman Methodology Scores were calculated to assess study methodological quality. Results Ten studies with a total of 610 patients with an average age of 27.0 years at the time of surgery and a mean follow‐up of 10.2 years were included. The mean defect size was 2.6 cm 2 (range, 0.9 to 20.0 cm 2 ). The mean duration of symptoms before surgery was 4.8 years. From preoperative to final follow‐up, International Knee Documentation Committee scores and Lysholm scores improved significantly by 42.4 (95% confidence interval [CI], 31.8 to 53.1, P < .001) and 21.1 (95% CI, 12.2 to 30.0, P < .01), respectively. Tegner score did not improve significantly (0.76, 95% CI, −0.83 to 2.36, P = .35). Overall failure rate was 28% and reoperation rate was 19%. Increased age, previous surgery, and defect size positively correlated with increased risk of failure. Concomitant surgical procedures negatively correlated with failure rate. Conclusions Overall, OAT showed successful outcomes in 72% of patients at long‐term follow‐up. Increased age, previous surgery, and defect size correlated positively with failure rate, whereas success improved with concomitant surgical procedures. Nonetheless, this systematic review is limited by heterogeneity in a surgical technique, lesion and patient characteristics, and reporting of nonstandardized outcome measures. Level of Evidence Level IV, systematic review of Level I‐IV studies.