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BackgroundLytic 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.PurposeTo 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 designCohort study; Level of evidence, 3.MethodsA 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.ResultsA 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.ConclusionTunnel 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.

We prospectively investigated the performance of the prostate-specific membrane antigen (PSMA) ligand 68Ga-PSMA-11 for detecting prostate adenocarcinoma in patients with elevated levels of prostate-specific antigen (PSA) after initial therapy. Methods:68Ga-PSMA-11 hybrid PET was performed on 2,005 patients at the time of biochemically recurrent prostate cancer after radical prostatectomy (RP) (50.8%), definitive radiation therapy (RT) (19.7%), or RP with postoperative RT (PORT) (29.6%). The presence of prostate cancer was assessed qualitatively (detection rate = positivity rate) and quantitatively on a per-patient and per-region basis, creating a disease burden estimate from the presence or absence of local (prostate/prostate bed), nodal (N1: pelvis), and distant metastatic (M1: distant soft tissue and bone) disease. The primary study endpoint was the positive predictive value (PPV) of 68Ga-PSMA-11 PET/CT confirmed by histopathology. Results: After RP, the scan detection rate increased significantly with rising PSA level (44.8% at PSA  10 ng/mL; P

BackgroundAlthough 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.HypothesisIn 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 designCohort study; Level of evidence, 2.MethodsPatients 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.ResultsA 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).ConclusionBTB 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.

BackgroundThere is a significant gap in our understanding of the sources of multidrug-resistant bacteria and resistance genes in community settings where human-animal interfaces exist.ObjectivesThis study characterized the relationship of third-generation cephalosporin-resistant Escherichia coli (3GCR-EC) isolated from animal feces in the environment and child feces based on phenotypic antimicrobial resistance (AMR) and whole genome sequencing (WGS).MethodsWe examined 3GCR-EC isolated from environmental fecal samples of domestic animals and child fecal samples in Ecuador. We analyzed phenotypic and genotypic AMR, as well as clonal relationships (CRs) based on pairwise single-nucleotide polymorphisms (SNPs) analysis of 3GCR-EC core genomes. CRs were defined as isolates with fewer than 100 different SNPs.ResultsA total of 264 3GCR-EC isolates from children (n=21), dogs (n=20), and chickens (n=18) living in the same region of Quito, Ecuador, were identified. We detected 16 CRs total, which were found between 7 children and 5 domestic animals (5 CRs) and between 19 domestic animals (11 CRs). We observed that several clonally related 3GCR-EC isolates had acquired different plasmids and AMR genes. Most CRs were observed in different homes (n=14) at relatively large distances. Isolates from children and domestic animals shared the same blaCTX-M allelic variants, and the most prevalent were blaCTX-M-55 and blaCTX-M-65, which were found in isolates from children, dogs, and chickens.DiscussionThis study provides evidence of highly dynamic horizontal transfer of AMR genes and mobile genetic elements (MGEs) in the E. coli community and shows that some 3GCR-EC and (extended-spectrum β-lactamase) ESBL genes may have moved relatively large distances among domestic animals and children in semirural communities near Quito, Ecuador. Child-animal contact and the presence of domestic animal feces in the environment potentially serve as important sources of drug-resistant bacteria and ESBL genes. https://doi.org/10.1289/EHP7729.

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.

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery1. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7, a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min)2. In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.

BackgroundPatient-reported outcomes (PROs) are a valid measure of results after revision anterior cruciate ligament (ACL) reconstruction. Revision ACL reconstruction has been documented to have worse outcomes when compared with primary ACL reconstruction. Understanding positive and negative predictors of PROs will allow surgeons to modify and potentially improve outcome for patients.Purpose/hypothesisThe purpose was to describe PROs after revision ACL reconstruction and test the hypothesis that patient- and technique-specific variables are associated with these outcomes.Study designCohort study; Level of evidence, 2.MethodsPatients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons over 52 sites. Data included baseline demographics, surgical technique and pathology, and a series of validated PRO 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. Patients were followed up at 2 years and asked to complete the identical set of outcome instruments. Multivariate regression models were used to control for a variety of demographic and surgical factors to determine the positive and negative predictors of PRO scores at 2 years after revision surgery.ResultsA total of 1205 patients met the inclusion criteria and were successfully enrolled: 697 (58%) were male, with a median cohort age of 26 years. The median time since their most recent previous ACL reconstruction was 3.4 years. Two-year questionnaire follow-up was obtained from 989 patients (82%). The most significant positive predictors of 2-year IKDC scores were a high baseline IKDC score, high baseline Marx activity level, male sex, and having a longer time since the most recent previous ACL reconstruction, while negative predictors included having a lateral meniscectomy before the revision ACL reconstruction or having grade 3/4 chondrosis in either the trochlear groove or the medial tibial plateau at the time of the revision surgery. For KOOS, having a high baseline score and having a longer time between the most recent previous ACL reconstruction and revision surgery were significant positive predictors for having a better (ie, higher) 2-year KOOS, while having a lateral meniscectomy before the revision ACL reconstruction was a consistent predictor for having a significantly worse (ie, lower) 2-year KOOS. Statistically significant positive predictors for 2-year Marx activity levels included higher baseline Marx activity levels, younger age, male sex, and being a nonsmoker. Negative 2-year activity level predictors included having an allograft or a biologic enhancement at the time of revision surgery.ConclusionPROs after revision ACL reconstruction are associated with a variety of patient- and surgeon-related variables. Understanding positive and negative predictors of PROs will allow surgeons to guide patient expectations as well as potentially improve outcomes.

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 < .0001), KOOS-Symptoms (P = .01), KOOS-Sports and Recreation (P = .04), and KOOS-Quality of Life (P < .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.

BackgroundRevision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes than primary ACL reconstruction. The reasons remain varied and not completely understood.MethodsPatients 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.ResultsA 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.ConclusionsRehabilitation-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 evidencePrognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

BackgroundThe occurrence of physiologic knee hyperextension (HE) in the revision anterior cruciate ligament reconstruction (ACLR) population and its effect on outcomes have yet to be reported. Hypothesis/Purpose: The prevalence of knee HE in revision ACLR and its effect on 2-year outcome were studied with the hypothesis that preoperative physiologic knee HE ≥5° is a risk factor for anterior cruciate ligament (ACL) graft rupture.Study designCohort study; Level of evidence, 2.MethodsPatients undergoing revision ACLR were identified and prospectively enrolled between 2006 and 2011. Study inclusion criteria were patients undergoing single-bundle graft reconstructions. Patients were followed up at 2 years and asked to complete an identical set of outcome instruments (International Knee Documentation Committee, Knee injury and Osteoarthritis Outcome Score, WOMAC, and Marx Activity Rating Scale) as well as provide information regarding revision ACL graft failure. A regression model with graft failure as the dependent variable included age, sex, graft type at the time of the revision ACL surgery, and physiologic preoperative passive HE ≥5° (yes/no) to assess these as potential risk factors for clinical outcomes 2 years after revision ACLR.ResultsAnalyses included 1145 patients, for whom 2-year follow-up was attained for 91%. The median age was 26 years, with age being a continuous variable. Those below the median were grouped as "younger" and those above as "older" (age: interquartile range = 20, 35 years), and 42% of patients were female. There were 50% autografts, 48% allografts, and 2% that had a combination of autograft plus allograft. Passive knee HE ≥5° was present in 374 (33%) patients in the revision cohort, with 52% being female. Graft rupture at 2-year follow-up occurred in 34 cases in the entire cohort, of which 12 were in the HE ≥5° group (3.2% failure rate) and 22 in the non-HE group (2.9% failure rate). The median age of patients who failed was 19 years, as opposed to 26 years for those with intact grafts. Three variables in the regression model were significant predictors of graft failure: younger age (odds ratio [OR] = 3.6; 95% CI, 1.6-7.9; P = .002), use of allograft (OR = 3.3; 95% CI, 1.5-7.4; P = .003), and HE ≥5° (OR = 2.12; 95% CI, 1.1-4.7; P = .03).ConclusionThis study revealed that preoperative physiologic passive knee HE ≥5° is present in one-third of patients who undergo revision ACLR. HE ≥5° was an independent significant predictor of graft failure after revision ACLR with a >2-fold OR of subsequent graft rupture in revision ACL surgery. Registration: NCT00625885 ( ClinicalTrials.gov identifier).

BackgroundArticular cartilage health is an important issue following anterior cruciate ligament (ACL) injury and primary ACL reconstruction. Factors present at the time of primary ACL reconstruction may influence the subsequent progression of articular cartilage damage.HypothesisLarger meniscus resection at primary ACL reconstruction, increased patient age, and increased body mass index (BMI) are associated with increased odds of worsened articular cartilage damage at the time of revision ACL reconstruction.Study designCase-control study; Level of evidence, 3.MethodsSubjects who had primary and revision data in the databases of the Multicenter Orthopaedics Outcomes Network (MOON) and Multicenter ACL Revision Study (MARS) were included. Reviewed data included chondral surface status at the time of primary and revision surgery, meniscus status at the time of primary reconstruction, primary reconstruction graft type, time from primary to revision ACL surgery, as well as demographics and Marx activity score at the time of revision. Significant progression of articular cartilage damage was defined in each compartment according to progression on the modified Outerbridge scale (increase ≥1 grade) or >25% enlargement in any area of damage. Logistic regression identified predictors of significant chondral surface change in each compartment from primary to revision surgery.ResultsA total of 134 patients were included, with a median age of 19.5 years at revision surgery. Progression of articular cartilage damage was noted in 34 patients (25.4%) in the lateral compartment, 32 (23.9%) in the medial compartment, and 31 (23.1%) in the patellofemoral compartment. For the lateral compartment, patients who had >33% of the lateral meniscus excised at primary reconstruction had 16.9-times greater odds of progression of articular cartilage injury than those with an intact lateral meniscus ( P < .001). For the medial compartment, patients who had

BackgroundRevision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes compared with primary ACL reconstruction.HypothesisCertain factors under the control of the surgeon at the time of revision surgery can both negatively and positively affect outcomes.Study designCase-control study; Level of evidence, 3.MethodsPatients undergoing revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline demographics, intraoperative surgical technique and joint disorders, and a series of validated patient-reported outcome instruments (International Knee Documentation Committee [IKDC] subjective form, Knee Injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], and Marx activity rating scale) completed before surgery. Patients were followed up for 2 years and asked to complete an identical set of outcome instruments. Regression analysis was used to control for age, sex, body mass index (BMI), activity level, baseline outcome scores, revision number, time since last ACL reconstruction, and a variety of previous and current surgical variables to assess the surgical risk factors for clinical outcomes 2 years after revision ACL reconstruction.ResultsA total of 1205 patients (697 male [58%]) met the inclusion criteria and were successfully enrolled. The median age was 26 years, and the median time since their last ACL reconstruction was 3.4 years. Two-year follow-up was obtained on 82% (989/1205). Both previous and current surgical factors were found to be significant contributors toward poorer clinical outcomes at 2 years. Having undergone previous arthrotomy (nonarthroscopic open approach) for ACL reconstruction compared with the 1-incision technique resulted in significantly poorer outcomes for the 2-year IKDC ( P = .037; odds ratio [OR], 2.43; 95% CI, 1.05-5.88) and KOOS pain, sports/recreation, and quality of life (QOL) subscales ( P ≤ .05; OR range, 2.38-4.35; 95% CI, 1.03-10.00). The use of a metal interference screw for current femoral fixation resulted in significantly better outcomes for the 2-year KOOS symptoms, pain, and QOL subscales ( P ≤ .05; OR range, 1.70-1.96; 95% CI, 1.00-3.33) as well as WOMAC stiffness subscale ( P = .041; OR, 1.75; 95% CI, 1.02-3.03). Not performing notchplasty at revision significantly improved 2-year outcomes for the IKDC ( P = .013; OR, 1.47; 95% CI, 1.08-1.99), KOOS activities of daily living (ADL) and QOL subscales ( P ≤ .04; OR range, 1.40-1.41; 95% CI, 1.03-1.93), and WOMAC stiffness and ADL subscales ( P ≤ .04; OR range, 1.41-1.49; 95% CI, 1.03-2.05). Factors before revision ACL reconstruction that increased the risk of poorer clinical outcomes at 2 years included lower baseline outcome scores, a lower Marx activity score at the time of revision, a higher BMI, female sex, and a shorter time since the patient's last ACL reconstruction. Prior femoral fixation, prior femoral tunnel aperture position, and knee flexion angle at the time of revision graft fixation were not found to affect 2-year outcomes in this revision cohort.ConclusionThere are certain surgical variables that the physician can control at the time of revision ACL reconstruction that can modify clinical outcomes at 2 years. Whenever possible, opting for an anteromedial portal or transtibial surgical exposure, choosing a metal interference screw for femoral fixation, and not performing notchplasty are associated with significantly better 2-year clinical outcomes.

BackgroundRevision anterior cruciate ligament (ACL) reconstruction has been documented to have worse outcomes compared with primary ACL reconstructions.Purpose/hypothesisThe purpose of this study was to determine if the prevalence, location, and/or degree of meniscal and chondral damage noted at the time of revision ACL reconstruction predicts activity level, sports function, and osteoarthritis symptoms at 2-year follow-up. The hypothesis was that meniscal loss and high-grade chondral damage noted at the time of revision ACL reconstruction will result in lower activity levels, decreased sports participation, more pain, more stiffness, and more functional limitation at 2 years after revision surgery.Study designCohort study; Level of evidence, 2.MethodsBetween 2006 and 2011, a total of 1205 patients who underwent revision ACL reconstruction by 83 surgeons at 52 hospitals were accumulated for study of the relationship of meniscal and articular cartilage damage to outcome. Baseline demographic and intraoperative data, including the International Knee Documentation Committee (IKDC) subjective knee evaluation, Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity score, were collected initially and at 2-year follow-up to test the hypothesis. Regression analysis was used to control for age, sex, body mass index, smoking status, activity level, baseline outcome scores, revision number, time since last ACL reconstruction, incidence of having a previous ACL reconstruction on the contralateral knee, previous and current meniscal and articular cartilage injury, graft choice, and surgeon years of experience to assess the meniscal and articular cartilage risk factors for clinical outcomes 2 years after revision ACL reconstruction.ResultsAt 2-year follow-up, 82% (989/1205) of the patients returned their questionnaires. It was found that previous meniscal injury and current articular cartilage damage were associated with the poorest outcomes, with prior lateral meniscectomy and current grade 3 to 4 trochlear articular cartilage changes having the worst outcome scores. Activity levels at 2 years were not affected by meniscal or articular cartilage pathologic changes.ConclusionPrior lateral meniscectomy and current grade 3 to 4 changes of the trochlea were associated with worse outcomes in terms of decreased sports participation, more pain, more stiffness, and more functional limitation at 2 years after revision surgery, but they had no effect on activity levels.RegistrationNCT00625885.

Spatial smoothing is an essential step in the analysis of functional magnetic resonance imaging (fMRI) data. One standard smoothing method is to convolve the image data with a three-dimensional Gaussian kernel that applies a fixed amount of smoothing to the entire image. In pre-surgical brain image analysis where spatial accuracy is paramount, this method, however, is not reasonable as it can blur the boundaries between activated and deactivated regions of the brain. Moreover, while in a standard fMRI analysis strict false positive control is desired, for pre-surgical planning false negatives are of greater concern. To this end, we propose a novel spatially adaptive conditionally autoregressive model with variances in the full conditional of the means that are proportional to error variances, allowing the degree of smoothing to vary across the brain. Additionally, we present a new loss function that allows for the asymmetric treatment of false positives and false negatives. We compare our proposed model with two existing spatially adaptive conditionally autoregressive models. Simulation studies show that our model outperforms these other models; as a real model application, we apply the proposed model to the pre-surgical fMRI data of two patients to assess peri- and intra-tumoral brain activity.

BackgroundKnees undergoing revision anterior cruciate ligament reconstruction (rACLR) have a high prevalence of articular cartilage lesions.HypothesisThe prevalence of chondrosis at the time of rACLR is associated with meniscal status and lower extremity alignment.Study designCross-sectional study; Level of evidence, 3.MethodsData 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.ResultsThe 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%.ConclusionThe 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.

BackgroundAnterior cruciate ligament (ACL) reconstruction failure occurs in up to 10% of cases. Technical errors are considered the most common cause of graft failure despite the absence of validated studies. Limited data are available regarding the agreement among orthopaedic surgeons regarding the causes of primary ACL reconstruction failure and accuracy of graft tunnel placement.HypothesisExperienced knee surgeons have a high level of interobserver reliability in the agreement about the causes of primary ACL reconstruction failure, anatomic graft characteristics, and tunnel placement.Study designCohort study (diagnosis); Level of evidence, 3.MethodsTwenty cases of revision ACL reconstruction were randomly selected from the Multicenter ACL Revision Study (MARS) database. Each case included the patient's history, standardized radiographs, and a concise 30-second arthroscopic video taken at the time of revision demonstrating the graft remnant and location of the tunnel apertures. All 20 cases were reviewed by 10 MARS surgeons not involved with the primary surgery. Each surgeon completed a 2-part questionnaire dealing with each surgeon's training and practice, as well as the placement of the femoral and tibial tunnels, condition of the primary graft, and the surgeon's opinion as to the causes of graft failure. Interrater agreement was determined for each question with the kappa coefficient and the prevalence-adjusted, bias-adjusted kappa (PABAK).ResultsThe 10 reviewers have been in practice an average of 14 years and have performed at least 25 ACL reconstructions per year, and 9 were fellowship trained in sports medicine. There was wide variability in agreement among knee experts as to the specific causes of ACL graft failure. When participants were specifically asked about technical error as the cause for failure, interobserver agreement was only slight (PABAK = 0.26). There was fair overall agreement on ideal femoral tunnel placement (PABAK = 0.55) but only slight agreement on whether a femoral tunnel was too anterior (PABAK = 0.24) and fair agreement on whether it was too vertical (PABAK = 0.46). There was poor overall agreement for ideal tibial tunnel placement (PABAK = 0.17).ConclusionThis study suggests that more objective criteria are needed to accurately determine the causes of primary ACL graft failure as well as the ideal femoral and tibial tunnel placement in patients undergoing revision ACL reconstruction.

BackgroundOsteoarthritis 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.MethodsAs 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.ResultsOverall, 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.ConclusionsThe 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 evidenceDiagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

BackgroundThe effects of primary tumor size on nodal involvement and of number of involved nodes on survival have not, to our knowledge, been examined in a national database of Merkel cell carcinoma (MCC).ObjectiveWe sought to analyze a retrospective cohort of patients with MCC from the largest US national database to assess the relationships between these clinical parameters and survival.MethodsA total of 8044 MCC cases in the National Cancer Data Base were analyzed.ResultsThere was a 14% risk of regional nodal involvement for 0.5-cm tumors that increased to 25% for 1.7-cm (median-sized) tumors and to more than 36% for tumors 6 cm or larger. The number of involved nodes was strongly predictive of survival (0 nodes, 76% 5-year relative survival; 1 node, 50%; 2 nodes, 47%; 3-5 nodes, 42%; and ≥6 nodes, 24%; P < .0001 for trend). Younger and/or male patients were more likely to undergo pathological nodal evaluation.LimitationsThe National Cancer Data Base does not capture disease-specific survival. Hence, relative survival was calculated by comparing overall survival with age- and sex-matched US population data.ConclusionPathologic nodal evaluation should be considered even for patients with small primary MCC tumors. The number of involved nodes is strongly predictive of survival and may help improve prognostic accuracy and management.

BackgroundThe factors that lead to patients failing multiple anterior cruciate ligament (ACL) reconstructions are not well understood.HypothesisMultiple-revision ACL reconstruction will have different characteristics than first-time revision in terms of previous and current graft selection, mode of failure, chondral/meniscal injuries, and surgical charactieristics.Study designCase-control study; Level of evidence, 3.MethodsA prospective multicenter ACL revision database was utilized for the time period from March 2006 to June 2011. Patients were divided into those who underwent a single-revision ACL reconstruction and those who underwent multiple-revision ACL reconstructions. The primary outcome variable was Marx activity level. Primary data analyses between the groups included a comparison of graft type, perceived mechanism of failure, associated injury (meniscus, ligament, and cartilage), reconstruction type, and tunnel position. Data were compared by analysis of variance with a post hoc Tukey test.ResultsA total of 1200 patients (58% men; median age, 26 years) were enrolled, with 1049 (87%) patients having a primary revision and 151 (13%) patients having a second or subsequent revision. Marx activity levels were significantly higher (9.77) in the primary-revision group than in those patients with multiple revisions (6.74). The most common cause of reruptures was a traumatic, noncontact ACL graft injury in 55% of primary-revision patients; 25% of patients had a nontraumatic, gradual-onset recurrent injury, and 11% had a traumatic, contact injury. In the multiple-revision group, a nontraumatic, gradual-onset injury was the most common cause of recurrence (47%), followed by traumatic noncontact (35%) and nontraumatic sudden onset (11%) (P < .01 between groups). Chondral injuries in the medial compartment were significantly more common in the multiple-revision group than in the single-revision group, as were chondral injuries in the patellofemoral compartment.ConclusionPatients with multiple-revision ACL reconstructions had lower activity levels, were more likely to have chondral injuries in the medial and patellofemoral compartments, and had a high rate of a nontraumatic, recurrent injury of their graft.

Surveys are an important research modality in ophthalmology, but their quality has not been rigorously assessed. This study evaluated the quality of published ophthalmic surveys. Three survey methodologists, three senior ophthalmologists, and two research assistants developed a survey evaluation instrument focused on survey development and testing; sampling frame; response bias; results reporting; and ethics. Two investigators used the instrument to assess the quality of all ophthalmic surveys that were published between January 1, 2018 and December 31, 2018; indexed in MEDLINE/PubMed, Embase, and/or Web of Science; contained the search terms "ophthalmology" and "survey" or "questionnaire" in the title and/or abstract; and were available in English. The search identified 626 articles; 60 met the eligibility criteria and were assessed with the survey evaluation instrument. Most surveys (93%; 56/60) defined the study population; 48% (29/60) described how question items were chosen; 30% (18/60) provided the survey for review or described the questions in sufficient detail; 30% (18/60) were pre-tested or piloted; 25% (15/60) reported validity/clinical sensibility testing; 15% (9/60) described techniques used to assess non-response bias; and 63% (38/60) documented review by an institutional review board (IRB). The quality of published ophthalmic surveys can be improved by focusing on survey development, pilot testing, non-response bias and institutional review board review. The survey evaluation instrument can help guide researchers in conducting quality ophthalmic surveys and assist journal editors in evaluating surveys submitted for publication. [ABSTRACT FROM AUTHOR]

Background: In 2006, the Clinical and Translational Science Award (CTSA), initiated by the National Center for Research Resources, was launched, with the overall goal to improve human health through clinical translational research. The purpose of this study was to examine the association between the total visit length for standardized study visits requiring the services of either a physician colleague or a designated advanced practice nurse (APN) for a protocol conducted in a clinical research center (CRC) supported with CTSA funds. Methods: Data collected for administrative purposes between June 2008 and September 2009 were used. This retrospective study compared the total visit length for the standardized study visits of a single study protocol requiring a gluteal fat biopsy procedure performed by either a physician colleague (an MD in this case) or a CRC-based APN employed by the CRC. Results: During the observed time period, 67 gluteal fat biopsy procedures were performed by one physician colleague, and 33 procedures were performed by one CRC-based APN. The mean total visit length of standardized study visits for research subjects treated by the physician colleague was 192.9±65.8 minutes, whereas the mean total visit length of standardized study visits for research subjects treated by the APN was 154.8±40.9 minutes (P=.003). Generalized least squares random effects regression model further evaluated the association between provider and visit length while controlling for age, gender, percent body fat and physical activity. The type of provider (P<.001) and gender (P<.05) were associated with length of visit. Conclusions: The introduction of a CRC-based APN to perform advanced procedures demonstrates an efficient use of resources to meet the advanced clinical needs of specific research protocols. In this retrospective study, the ready availability of an APN (employed by the CRC) to perform gluteal fat biopsies during standardized study visits led to a decrease in total visit length, and thus a more rapid "turnover" of clinical research space compared to the use of a physician colleague. To best meet the needs of clinical researchers, CRCs should consider the employment of other clinicians to complement the research facilitation services provided by registered nurses. The addition of an APN to the CRC research facilitation team is novel and lends itself to the spirit of the clinical translational research initiative; additional studies evaluating the contribution of other licensed practitioners to improve research facilitation efficiency are needed. [ABSTRACT FROM AUTHOR]