Impact of Sports Participation on Achievement of Clinically Relevant Outcomes 2 Years After ACL Reconstruction.

Background: Clinically relevant threshold values associated with patient-reported outcome measures after orthopaedic procedures such as anterior cruciate ligament reconstruction (ACLR) are important for relating these scores to meaningful postoperative improvement. Purpose/Hypothesis: The purpose of this study was to determine the Patient Acceptable Symptom State (PASS) for the Patient-Reported Outcomes Measurement Information System Computer Adaptive Test (PROMIS-CAT) after ACLR. It was hypothesized that preoperative sport participation would have an impact on PASS achievement. Study Design: Case series; Level of evidence, 4. Methods: Included were consecutive patients who underwent primary assisted ACLR between January 4 and August 1, 2016. Patients were administered the PROMIS-CAT Physical Function (PF) and Pain Interference domains preoperatively and at a minimum 2 years postoperatively, with external anchor questions used to determine the PASS. Receiver operating characteristic (ROC) curves were constructed for the entire study population as well as separately for athletes and nonathletes to determine PROMIS PASS thresholds for each population. A previously published PROMIS-PF minimal clinically important difference was used to evaluate postoperative improvement. A post hoc multivariate nominal logistic multivariate analysis was constructed to assess the effects of preoperative patient characteristics on the likelihood of attaining both the minimal clinically important difference and PASS. Results: In total, 112 patients were included in the study, with 79 (71%) having recreational or higher levels of athletic participation. The PASS for the study population was 56.0 (area under the ROC curve, 0.86) and was unaffected by baseline PROMIS-PF scores but was affected by preoperative athletic participation (56.0 for athletes, 49.0 for nonathletes). A post hoc analysis found 57 patients (51%) achieved the PASS for the PROMIS-PF (cutoff, 56.0), but when the athlete and nonathlete thresholds were applied to their respective patient groups, 66% of athletes and 64% of nonathletes achieved the PASS postoperatively. The multivariate analysis found that sport participation (odds ratio, 6.2; P = .001) but not age, sex, body mass index, or preoperative PROMIS affected the likelihood of achieving the PASS on the PROMIS-PF. Conclusion: Preoperative athletic participation significantly affected the ability to achieve PASS.

Patient-Reported Outcomes Are Similar in the First 2 Years After Staged Versus Combined Hip Arthroscopy and Periacetabular Osteotomy for Hip Dysplasia.

PURPOSE: To compare early patient-reported outcomes after staged versus combined hip arthroscopy and periacetabular osteotomy for hip dysplasia. METHODS: A prospective database was retrospectively reviewed to identify patients that underwent combined or staged hip arthroscopy and periacetabular osteotomy (PAO) from 2012 to 2020. Patients were excluded if they were >40 years of age, had prior ipsilateral hip surgery, or did not have at least 12-24 months of postoperative patient-reported outcome (PRO) data. PROs included the Hip Outcomes Score (HOS) Activities of Daily Living (ADL) and Sports Subscale (SS), Non-Arthritic Hip Score (NAHS), and the Modified Harris Hip Score (mHHS). Paired t-tests were used to compare preoperative to postoperative scores for both groups. Outcomes were compared using linear regression adjusted for baseline characteristics, including age, obesity, cartilage damage, acetabular index, and procedure timing (early vs late practice). RESULTS: Sixty-two hips were included in this analysis (39 combined, 23 staged). The average length of follow-up was similar between the combined and staged groups (20.8 vs 19.6 months; P = .192). Both groups reported significant improvements in PROs at final follow up compared to preoperative scores (P < .05 for all). There were no significant differences in HOS-ADL, HOS-SS, NAHS, or mHHS scores between groups preoperatively or at 3, 6, or 12 months postoperatively (P > .05 for all). There was no significant difference in PROs between the combined and staged groups at the final postoperative time point: HOS-ADL (84.5 vs 84.3; P = .77), HOS-SS (76.0 vs 79.2; P = .68), NAHS (82.2 vs 84.5; P = .79), and mHHS (71.0 vs 71.0, P = .75), respectively. CONCLUSIONS: Staged hip arthroscopy and PAO for hip dysplasia leads to similar PROs at 12-24 months compared to combined procedures. This suggests that with careful and informed patient selection, staging these procedures is an acceptable option for these patients and does not change early outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Whole-genome RNA sequencing identifies distinct transcriptomic profiles in impingement cartilage between patients with femoroacetabular impingement and hip osteoarthritis.

Femoroacetabular impingement (FAI) has a strong clinical association with the development of hip osteoarthritis (OA); however, the pathobiological mechanisms underlying the transition from focal impingement to global joint degeneration remain poorly understood. The purpose of this study is to use whole-genome RNA sequencing to identify and subsequently validate differentially expressed genes (DEGs) in femoral head articular cartilage samples from patients with FAI and hip OA secondary to FAI. Thirty-seven patients were included in the study with whole-genome RNA sequencing performed on 10 gender-matched patients in the FAI and OA cohorts and the remaining specimens were used for validation analyses. We identified a total of 3531 DEGs between the FAI and OA cohorts with multiple targets for genes implicated in canonical OA pathways. Quantitative reverse transcription-polymerase chain reaction validation confirmed increased expression of FGF18 and WNT16 in the FAI samples, while there was increased expression of MMP13 and ADAMTS4 in the OA samples. Expression levels of FGF18 and WNT16 were also higher in FAI samples with mild cartilage damage compared to FAI samples with severe cartilage damage or OA cartilage. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. We independently validated the results of the sequencing analysis and found increased expression of anabolic markers in patients with FAI and minimal histologic cartilage damage, suggesting that anabolic signaling may be increased in early FAI with a transition to catabolic and inflammatory gene expression as FAI progresses towards more severe hip OA. Clinical significance:Cam-type FAI has a strong clinical association with hip OA; however, the cellular pathophysiology of disease progression remains poorly understood. Several previous studies have demonstrated increased expression of inflammatory markers in FAI cartilage samples, suggesting the involvement of these inflammatory pathways in the disease progression. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. In addition to differences in inflammatory gene expression, we also identified differential expression in multiple pathways involved in hip OA progression.

The surgical destabilization of the abductor muscle leads to development of instability-associated hip osteoarthritis in mice.

Osteoarthritis (OA) of the hip is a common and debilitating painful joint disease. However, there is paucity of surgically induced hip OA models in small animals that allow scientists to study the onset and progression of the disease. A growing body of evidence indicates a positive association between periarticular myotendinous pathology and the development of hip OA. Thus, in the current study, we aimed to establish a novel mouse instability-associated hip OA model via selective injury of the abductor complex around the hip joint. C57BL6/J mice were randomized to sham surgery or abductor injury, in which the myotendinous insertion at the third trochanter and greater trochanter were surgically detached. Mice were allowed free active movement until they were sacrificed at either 3 weeks or 20 weeks post-injury. Histologic analyses and immunohistochemical staining of the femoral head articular cartilage were performed, along with microCT (µCT) analysis to assess subchondral bone remodeling. We observed that mice receiving abductor injury exhibited significantly increased instability-associated OA severity with loss of proteoglycan and type II collagen staining compared to sham control mice at 20 weeks post-surgery, while comparable matrix metalloproteinase 13 expression was observed between injury and sham groups. No significant differences in subchondral bone remodeling were found after 3 or 20 weeks following injury. Our study further supports the link between abductor dysfunction and the development of instability-associated hip OA. Importantly, this novel surgically induced hip OA mouse model may provide a valuable tool for future investigations into the pathogenesis and treatment of hip OA.

Clinically Depressed Patients Having Anterior Cruciate Ligament Reconstruction Show Improved but Inferior Rate of Achieving Minimum Clinically Important Difference for Patient-Reported Outcomes Measurement Information System Compared With Situationally Depressed or Nondepressed Patients.

PURPOSE: To determine whether the preoperative diagnosis of depression predicted worse postoperative outcomes, including physical therapy (PT) compliance, return-to-sport, and patient-reported outcomes using the Patient-Reported Outcomes Measurement Information System (PROMIS) after anterior cruciate ligament (ACL) reconstruction. METHODS: A multisurgeon series of consecutive patients who had undergone ACL reconstruction with minimum 2-year follow-up were included. Chart review was conducted to determine depression diagnosis status, demographic data, rehabilitation PT compliance, return to sports, and patient-reported outcome data using PROMIS. Patients who met the PROMIS threshold for mild depression but did not carry a clinical diagnosis of depression were classified as "situationally depressed." RESULTS: Ninety-five of 115 consecutive patients (81%) met inclusion criteria with an average follow-up of 34 ± 1.9 months. Fourteen patients (15%) had a preoperative diagnosis of depression, whereas 21 (22%) were considered situationally depressed. Clinically depressed patients had a greater rate of PT noncompliance (33.2% ± 17.6% vs 21.9% ± 12.6%; P = .02) and a lower postoperative PROMIS Physical Function (50.8 ± 7.7 vs 57.8 ± 11.0; P = .03 compared with patients without depression. Situationally depressed patients had lower preoperative physical function (35.4 vs 42.5; P = .04) with no differences in postoperative outcomes scores compared to the non-depressed cohort.19/21 (90.5%) of situationally depressed patients had postoperative resolution of their depressive symptoms. CONCLUSIONS: Situationally depressed patients without a clinical diagnosis of depression can expect significant improvements in both pain and function, as well as a resolution of their depressed mood based on PROMIS scores as they progress through recovery after ACL reconstruction. Clinically depressed patients also experience significant improvements; however, their rate of achieving the minimum clinically important difference for PROMIS outcomes may be less than their nondepressed or situationally depressed counterparts. LEVEL OF EVIDENCE: III, prognostic comparative trial.

Threshold Values for Success After Hip Arthroscopy Using the Patient-Reported Outcomes Measurement Information System Assessment: Determining the Minimum Clinically Important Difference and Patient Acceptable Symptomatic State.

BACKGROUND: Threshold values for patient-reported outcome measures, such as the minimum clinically important difference (MCID) and patient acceptable symptomatic state (PASS), are important for relating postoperative outcomes to meaningful functional improvement. PURPOSE: To determine the PASS and MCID after hip arthroscopy for femoroacetabular impingement using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: A consecutive series of patients undergoing primary hip arthroscopy for femoroacetabular impingement were administered preoperative and minimum 1-year postoperative PROMIS surveys focusing on physical function (PF) and pain interference (PI). External anchor questions for the MCID and PASS were given with the postoperative PROMIS survey. Receiver operator curves were constructed to determine the threshold values for the MCID and PASS. Curves were generated for the study population as well as separate cohorts segregated by median baseline PF or PI scores and preoperative athletic participation. A multivariate post hoc analysis was then constructed to evaluate factors associated with achieving the PASS or MCID. RESULTS: There were 113 patients (35% male; mean ± SD age, 32.8 ± 12.5 years; body mass index, 25.8 ± 4.8 kg/m2), with 60 (53%) reporting preoperative athletic participation. Survey time averaged 77.5 ± 49.2 seconds. Anchor-based MCID values were 5.1 and 10.9 for the PF and PI domains, respectively. PASS thresholds were 51.8 and 51.9 for the PF and PI, respectively. PASS values were not affected by baseline scores, but athletic patients had a higher PASS threshold than did those not participating in a sport (53.1 vs 44.7). MCID values were affected by preoperative baseline scores but were largely independent of sports participation. A post hoc analysis found that 94 (83%) patients attained the MCID PF while 66 (58%) attained the PASS PF. A multivariate nominal logistic regression found that younger patients (P = .01) and athletic patients (P = .003) were more likely to attain the PASS. CONCLUSION: The PROMIS survey is an efficient metric to evaluate preoperative disability and postoperative function after primary hip arthroscopy for femoroacetabular impingement. The MCID and PASS provide surgeons with threshold values to help determine PROMIS scores that are clinically meaningful to patients, and they can assist with therapeutic decision making as well as expectation setting.

Characterizing Patient Preferences Surrounding Total Knee Arthroplasty.

BACKGROUND: Episode-based bundled payments for total knee arthroplasty emphasize cost-effective patient-centered care. Understanding patients' perceptions of components of the total knee arthroplasty care episode is critical to achieving this care. This study investigated patient preferences for components of the total knee arthroplasty care episode. METHODS: Best-worst scaling was used to analyze patient preferences for components of the total knee arthroplasty care episode. Participants were selected from patients presenting to 2 orthopaedic clinics with chronic knee pain. They were presented with descriptions of 17 attributes before completing a best-worst scaling exercise. Attribute importance was determined using hierarchical Bayesian estimation. Latent class analysis was used to evaluate varying preference profiles. RESULTS: One hundred and seventy-four patients completed the survey, and 117 patients (67%) were female. The mean age was 62.71 years. Participants placed the highest value on surgeon factors, including level of experience, satisfaction rating, and complication rates. Latent class analysis provided a 4-segment model of the population. CONCLUSIONS: This study demonstrated differences in patient preferences for the components of a total knee arthroplasty care episode and characterized distinct preference profiles among patient subsets. Stakeholders can use this information to focus efforts and policy on high-value components and to potentially create customized bundles guided by preference profiles. CLINICAL RELEVANCE: This study is clinically relevant because the patient preferences identified here may help providers to design customized bundles for total knee arthroplasty care.

The control of an invasive bivalve, Corbicula fluminea, using gas impermeable benthic barriers in a large natural lake.

Anoxia can restrict species establishment in aquatic systems and the artificial promotion of these conditions can provide an effective control strategy for invasive molluscs. Low abundances (2-20 m(-2)) of the nonnative bivalve, Asian clam (Corbicula fluminea), were first recorded in Lake Tahoe, CA-NV in 2002 and by 2010 nuisance-level population densities (>10,000 m(-2)) were observed. A non-chemical control method using gas impermeable benthic barriers to reduce dissolved oxygen (DO) concentrations available to C. fluminea was tested in this ultra-oligotrophic natural lake. In 2009, the impact of ethylene propylene diene monomer (EPDM) sheets (9 m(2), n = 6) on C. fluminea beds was tested on 1-7 day intervals over a 56 day period (August-September). At an average water temperature of 18 °C, DO concentrations under these small barriers were reduced to zero after 72 h resulting in 100 % C. fluminea mortality after 28 days. In 2010, a large EPDM barrier (1,950 m(2)) was applied to C. fluminea populations for 120 days (July-November). C. fluminea abundances were reduced over 98 % after barrier removal, and remained significantly reduced (>90 %) 1 year later. Non-target benthic macroinvertebrate abundances were also reduced, with variable taxon-specific recolonization rates. High C. fluminea abundance under anoxic conditions increased the release of ammonium and soluble reactive phosphorus from the sediment substrate; but levels of unionized ammonia were low at 0.004-0.005 mg L(-1). Prolonged exposure to anoxia using benthic barriers can provide an effective short term control strategy for C. fluminea.

Lake warming favours small-sized planktonic diatom species.

Diatoms contribute to a substantial portion of primary production in the oceans and many lakes. Owing to their relatively heavy cell walls and high nutrient requirements, planktonic diatoms are expected to decrease with climate warming because of reduced nutrient redistribution and increasing sinking velocities. Using a historical dataset, this study shows that diatoms were able to maintain their biovolume with increasing stratification in Lake Tahoe over the last decades; however, the diatom community structure changed. Increased stratification and reduced nitrogen to phosphorus ratios selected for small-celled diatoms, particularly within the Cyclotella genus. An empirical model showed that a shift in phytoplankton species composition and cell size was consistent within different depth strata, indicating that altered nutrient concentrations were not responsible for the change. The increase in small-celled species was sufficient to decrease the average diatom size and thus sinking velocity, which strongly influences energy transfer through the food web and carbon cycling. Our results show that within the diverse group of diatoms, small-sized species with a high surface area to volume ratio were able to adapt to a decrease in mixing intensity, supporting the hypotheses that abiotic drivers affect the size structure of planktonic communities and that warmer climate favours small-sized diatom cells.

Modeling MTBE and BTEX in lakes and reservoirs used for recreational boating.

It is generally recognized that the bulk of fuel-related volatile organic compounds (VOCs) in lakes and reservoirs come from motorized recreational boating, but a quantitative connection between the two has been difficult to establish. A detailed boating use survey was conducted at a Northern California multiple-use lake, and the results were used to quantify daily methyl tert-butyl ether (MTBE) and benzene, toluene, ethylbenzene, and xylene (BTEX) loading from recreational boating. A one-dimensional, process-based numerical model was used to predict VOC levels as a function of the number, type, and activity of marine engines using the lake, the vertical mixing dynamics of the lake, and the volatilization rates of the individual VOCs. The model was validated on two other reservoirs to establish its applicability under a range of climatic and boating conditions. The study further confirmed the link between motorized boating and surface-water VOC contamination. In addition, the results of this study suggest that volatilization alone is inadequate to describe the loss of volatile hydrocarbons from surface waters and that some combination of additional degradation processes is involved. Under low wind conditions, these degradation processes dominate the removal of MTBE. For toluene, these processes are always more dominant than volatilization. The mean relative percent difference (RPD) between measured and simulated VOC concentrations at the study site, accounting only for volatilization losses, was 50.6% for MTBE and 113% for toluene. A first-order submodel was implemented to account for losses other than volatilization, using decay coefficients estimated from the literature. The resulting mean RPDs between measured and modeled concentrations were 14.2% for MTBE and 4.5% for toluene.

Dendritic development of Drosophila high order visual system neurons is independent of sensory experience.

BACKGROUND: The complex and characteristic structures of dendrites are a crucial part of the neuronal architecture that underlies brain function, and as such, their development has been a focal point of recent research. It is generally believed that dendritic development is controlled by a combination of endogenous genetic mechanisms and activity-dependent mechanisms. Therefore, it is of interest to test the relative contributions of these two types of mechanisms towards the construction of specific dendritic trees. In this study, we make use of the highly complex Vertical System (VS) of motion sensing neurons in the lobula plate of the Drosophila visual system to gauge the importance of visual input and synaptic activity to dendritic development. RESULTS: We find that the dendrites of VS1 neurons are unchanged in dark-reared flies as compared to control flies raised on a 12 hour light, 12 hour dark cycle. The dendrites of these flies show no differences from control in dendrite complexity, spine number, spine density, or axon complexity. Flies with genetically ablated eyes show a slight but significant reduction in the complexity and overall length of VS1 dendrites, although this effect may be due to a reduction in the overall size of the dendritic field in these flies. CONCLUSIONS: Overall, our results indicate no role for visual experience in the development of VS dendrites, while spontaneous activity from photoreceptors may play at most a subtle role in the formation of fully complex dendrites in these high-order visual processing neurons.

Small GTPase Cdc42 is required for multiple aspects of dendritic morphogenesis.

The study of dendritic development in CNS neurons has been hampered by a lack of complex dendritic structures that can be studied in a tractable genetic system. In an effort to develop such a system, we recently characterized the highly complex dendrites of the vertical system (VS) neurons in the Drosophila visual system. Using VS neurons as a model system, we show here using loss-of-function mutations that endogenous Cdc42, a member of Rho family of small GTPases, is required for multiple aspects of dendritic morphogenesis. Cdc42-mutant VS neurons display normal complexity but increased dendritic length compared with wild type and have defects in dendrite caliber and stereotyped dendritic branch positions. Remarkably, Cdc42 mutant neurons also show a 50% reduction in dendritic spine density. These results demonstrate that Cdc42 is a regulator for multiple aspects of dendritic development.

A mosaic genetic screen for genes necessary for Drosophila mushroom body neuronal morphogenesis.

Neurons undergo extensive morphogenesis during development. To systematically identify genes important for different aspects of neuronal morphogenesis, we performed a genetic screen using the MARCM system in the mushroom body (MB) neurons of the Drosophila brain. Mutations on the right arm of chromosome 2 (which contains approximately 20% of the Drosophila genome) were made homozygous in a small subset of uniquely labeled MB neurons. Independently mutagenized chromosomes (4600) were screened, yielding defects in neuroblast proliferation, cell size, membrane trafficking, and axon and dendrite morphogenesis. We report mutations that affect these different aspects of morphogenesis and phenotypically characterize a subset. We found that roadblock, which encodes a dynein light chain, exhibits reduced cell number in neuroblast clones, reduced dendritic complexity and defective axonal transport. These phenotypes are nearly identical to mutations in dynein heavy chain Dhc64 and in Lis1, the Drosophila homolog of human lissencephaly 1, reinforcing the role of the dynein complex in cell proliferation, dendritic morphogenesis and axonal transport. Phenotypic analysis of short stop/kakapo, which encodes a large cytoskeletal linker protein, reveals a novel function in regulating microtubule polarity in neurons. MB neurons mutant for flamingo, which encodes a seven transmembrane cadherin, extend processes beyond their wild-type dendritic territories. Overexpression of Flamingo results in axon retraction. Our results suggest that most genes involved in neuronal morphogenesis play multiple roles in different aspects of neural development, rather than performing a dedicated function limited to a specific process.