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Supplemental material, sj-docx-1-ajs-10.1177_03635465231151389 for Meniscal and Articular Cartilage Predictors of Outcome After Revision ACL Reconstruction: A 6-Year Follow-up Cohort Study by Rick W. Wright, Laura J. Huston, Amanda K. Haas, Jacquelyn S. Pennings, Christina R. Allen, Daniel E. Cooper, Thomas M. DeBerardino, Warren R. Dunn, Brett (Brick) A. Lantz, Kurt P. Spindler, Michael J. Stuart, John P. Albright, Annunziato (Ned) Amendola, Jack T. Andrish, Christopher C. Annunziata, Robert A. Arciero, Bernard R. Bach, Champ L. Baker, Arthur R. Bartolozzi, Keith M. Baumgarten, Jeffery R. Bechler, Jeffrey H. Berg, Geoffrey A. Bernas, Stephen F. Brockmeier, Robert H. Brophy, Charles A. Bush-Joseph, J. Brad Butler, John D. Campbell, James L. Carey, James E. Carpenter, Brian J. Cole, Jonathan M. Cooper, Charles L. Cox, R. Alexander Creighton, Diane L. Dahm, Tal S. David, David C. Flanigan, Robert W. Frederick, Theodore J. Ganley, Elizabeth A. Garofoli, Charles J. Gatt, Steven R. Gecha, James Robert Giffin, Sharon L. Hame, Jo A. Hannafin, Christopher D. Harner, Norman Lindsay Harris, Keith S. Hechtman, Elliott B. Hershman, Rudolf G. Hoellrich, David C. Johnson, Timothy S. Johnson, Morgan H. Jones, Christopher C. Kaeding, Ganesh V. Kamath, Thomas E. Klootwyk, Bruce A. Levy, C. Benjamin Ma, G. Peter Maiers, Robert G. Marx, Matthew J. Matava, Gregory M. Mathien, David R. McAllister, Eric C. McCarty, Robert G. McCormack, Bruce S. Miller, Carl W. Nissen, Daniel F. O’Neill, Brett D. Owens, Richard D. Parker, Mark L. Purnell, Arun J. Ramappa, Michael A. Rauh, Arthur C. Rettig, Jon K. Sekiya, Kevin G. Shea, Orrin H. Sherman, James R. Slauterbeck, Matthew V. Smith, Jeffrey T. Spang, LTC Steven J. Svoboda, Timothy N. Taft, Joachim J. Tenuta, Edwin M. Tingstad, Armando F. Vidal, Darius G. Viskontas, Richard A. White, James S. Williams, Michelle L. Wolcott, Brian R. Wolf and James J. York in The American Journal of Sports Medicine

Supplemental material, sj-pdf-1-ajs-10.1177_03635465231172769 for Predictors of Return to Activity at 2 Years After Anterior Cruciate Ligament Reconstruction Among Patients With High Preinjury Marx Activity Scores: A MOON Prospective Cohort Study by Andrew J. Sheean, Yuxuan Jin, Laura J. Huston, Robert H. Brophy, Charles L. Cox, David C. Flanigan, Morgan H. Jones, Christopher C. Kaeding, Robert A. Magnussen, Robert G. Marx, Matthew J. Matava, Eric C. McCarty, Richard D. Parker, Michelle L. Wolcott, Brian R. Wolf, Rick W. Wright and Kurt P. Spindler in The American Journal of Sports Medicine

BACKGROUND: Nerve injury can lead to ectopic activation of injured nociceptorsand central sensitization characterized by allodynia and hyperalgesia. Reduction in the activity of primary afferent neurons has been shown to be sufficient in alleviating peripherally generated pain. The cell bodies of such trigeminal nociceptors are located in the trigeminal ganglia (TG) with central processes that terminate in the brainstem trigeminal nucleus caudalis (TNC). The TG is therefore a strategic locus where afferent input can be manipulated. We hypothesized that chemogenetic inhibition of TG would suppress TNC neuronal activity and attenuate pain behaviour in a rat model of painful traumatic trigeminal neuropathy (PTTN). METHODS: Trigeminal neuropathic pain was induced in adult male Sprague–Dawley rats (n = 24) via chronic constriction injury to the infraorbital nerve (ION-CCI). Naïve and sham rats were used as controls (n = 20/group). Rats within each group received TG-directed microinjections of AAV virus containing either the inhibitory hM4Di-DREADD construct or EGFP. RESULTS: In the ION-CCI group, systemic administration of the DREADD agonist clozapine N-oxide (CNO) reversed the hypersensitivity phenotype in animals expressing hM4Di but not EGFP. CNO-mediated activation of hM4Di DREADD in ION-CCI animals was also associated with reduced Fos expression in the TNC elicited by repeated mechanical stimulation of the dermatome ipsilateral to the injury. There was no effect of CNO on pain behaviour or TNC Fos expression in eGFP animals. CONCLUSION: Our results indicate that DREADDs may offer an effective therapeutic approach for treatment of trigeminal neuropathic pain. SIGNIFICANCE: Trigeminal neuropathic pain is highly resistant to therapy and we are in dire need of novel approaches. This study provides further evidence for the successful application of DREADDs as an effective tool for modulating central nervous system function. CNO mediated activation of hM4Di-DREADDs in the trigeminal ganglion (TG) attenuates nerve injury induced neuropathic pain by acting on hyperactive TG cells. It also establishes the TG as an effective target to manage pain in the face and head. Accessing the TG in clinical populations is a relatively simple and safe procedure, making this approach highly significant. Moreover, the methodology described here has applications in trigeminal neuropathic pain from traumatic other etiologies and in spinal neuropathic pain. Chronic pain syndromes are characterized by a progressive failure of brain centers to adequately inhibit pain and as these are identified, we may be able to target them for therapy. Therefore, our findings might have wide application in chronic pain syndromes.

Although originally implicated in appetite and sleep/wakefulness, the hypothalamic orexin (hypocretin) system has now been demonstrably linked with motivated behavior. This highly plastic system responds to reward-associated environmental stimuli and becomes pathologically overactive in addicted states. Here, we provide a brief overview of the roles of the orexin system in reward-seeking and addiction, as well as potential therapeutic opportunities for substance use disorders based on normalizing orexin function.

The acute phase of the COVID-19 pandemic was associated with significant increases in the prevalence and severity of eating disorders (EDs). Studies also highlighted changes to sleep quality and duration in many individuals throughout this period. Although these two phenomena have been examined separately, here we highlight the need to investigate the potential link between these outcomes. Sleep dysregulation and EDs have previously been hypothesized to interact via a positive feedback loop, wherein poor sleep exacerbates ED symptomatology which, in turn, further worsens sleep. Thus, we speculate that the aggravation of sleep disturbances and EDs during COVID-19 lockdowns may have been somewhat interdependent. We further hypothesize that the worsening of depression and anxiety symptomology during the acute phase of the pandemic may have served as an additional mediating variable. Altogether, in our view, these observations highlight a need for future work to examine the possible causal relationship between sleep and ED pathology, which may ultimately lead to improved clinical management of disordered eating.

As opioid-related fatalities continue to rise, the need for novel opioid use disorder (OUD) treatments could not be more urgent. Two separate hypothalamic neuropeptide systems have shown promise in preclinical OUD models. The oxytocin system, originating in the paraventricular nucleus (PVN), may protect against OUD severity. By contrast, the orexin system, originating in the lateral hypothalamus (LH), may exacerbate OUD severity. Thus, activating the oxytocin system or inhibiting the orexin system are potential therapeutic strategies. The specific role of these systems with regard to specific OUD outcomes, however, is not fully understood. Here, we probed the therapeutic efficacy of pharmacological interventions targeting the orexin or oxytocin system on two distinct metrics of OUD severity in rats—heroin choice (versus choice for natural reward, i.e., food) and cued reward seeking. Using a preclinical model that generates approximately equal choice between heroin and food reward, we examined the impact of exogenously administered oxytocin, an oxytocin receptor antagonist (L-368,899), and a dual orexin receptor antagonist (DORA-12) on opioid choice. Whereas these agents did not alter heroin choice when rewards (heroin and food) were available, oxytocin and DORA-12 each significantly reduced heroin seeking in the presence of competing reward cues when no rewards were available. In addition, the number of LH orexin neurons and PVN oxytocin neurons correlated with specific behavioral economic variables indicative of heroin versus food motivation. These data identify a novel bidirectional role of the oxytocin and orexin systems in the ability of opioid-related cues to bias reward seeking.

The purpose of the present study was to examine whether Black patients presenting for arthroscopic partial meniscectomy (APM) have worse baseline knee pain, worse knee function, and greater articular cartilage damage than White patients.A cohort of 3,086 patients (84% of whom were White; 13%, Black; and 3%, other race, with a median age of 53 years) who underwent APM were enrolled. Patients who underwent concomitant procedures and patients of undisclosed race or self-pay status were excluded. The associations of race with the preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) for pain (KOOS-pain) and the KOOS-Physical Function Short Form (KOOS-function) and the intraoperative assessment of cartilage damage (highest modified Outerbridge grading) were determined by multivariate modeling with adjustment for age, sex, insurance status, years of education, smoking status, body mass index (BMI), meniscal tear location, and Veterans RAND 12-Item Health Survey Mental Component Summary (VR-12 MCS) score.The 3 factors most strongly associated with worse KOOS-pain and KOOS-function were a lower VR-12 MCS score, increased BMI, and increased age. The 3 factors most strongly associated with higher-grade articular cartilage damage were increased age, increased BMI, and meniscal tear location. All of these factors had an unequal distribution between Black and White patients. After adjusting for confounding variables, the KOOS-pain score for Black patients was a mean of 2.6 points lower than that for White patients regardless of insurance status; the KOOS-function score for Black patients with commercial insurance was a mean of 2.4 points lower than that for White patients with commercial insurance but was not lower than that for Black patients on Medicare. Compared with commercially insured White patients, commercially insured Black patients had 1.4-fold greater odds of having higher-grade articular damage, and no difference in risk was detected among Medicare-insured Black patients.There are clinically important differences in the distribution of risk factors between Black and White patients presenting for APM regarding several factors associated with worse knee pain, knee function, and greater articular cartilage damage. When controlling for these confounding factors, a significant, but not clinically relevant, racial disparity remained with respect to knee pain, knee function, and cartilage damage. Two of the 3 major risk factors for all 3 included age and BMI. The third factor for knee pain and function was mental health, and the location of a meniscal tear was the third factor for articular cartilage damage.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Inflammation is a potential pain generator and treatment target in knee osteoarthritis (OA). Inflammation can be detected on MRI and by synovial fluid white blood cell count (SF WBC). However, the performance characteristics of SF WBC for the detection of synovitis have not been established.We identified records of patients seen at an academic center with a diagnosis code for knee OA, a procedural code for knee aspiration and laboratory order for SF WBC in the same encounter, as well as an MRI within 12 months of the aspiration. MRIs were read for effusion synovitis (E-S) using the MRI OA Knee Score (MOAKS). We dichotomized E-S as: 1) none or small, or 2) medium or large. We calculated the sensitivity and specificity of SF WBC, using MRI E-S (medium/large) as the gold standard. We used Youden's Index to identify the best cut-point.We included 75 patients. Mean age was 63 y.o. (SD 12) and 69% were female. The SF WBC was higher in the medium/large E-S group (median = 335, IQR =312) than in the none/small group (median = 194, IQR =272). The optimal cut-point was 242, yielding a sensitivity of 71% (95% CI 56-83%) and specificity of 63% (95 % CI 41-81%).The sensitivity and specificity of SF WBC in identifying E-S on MRI were limited. Further research is needed to better understand the association between MRI and SF measured E-S and to determine which measure more strongly relates to synovial histopathology and patient outcomes.

Recently there has been a reckoning in the dopamine field. This has suggested that the dopamine prediction error may function as a teaching signal, without endowing preceding events with value. We studied the cognitive basis of intracranial self-stimulation (ICSS), a setting where dopamine appears to be valuable. Physiological frequencies seen during reinforcement learning did not support robust ICSS or promote behavior that would indicate the stimulation was represented as a meaningful reward in a specific or general sense. This was despite demonstrating that this same physiologically-relevant signal could function as a teaching signal. However, supraphysiological frequencies supported robust ICSS where the stimulation was represented as a specific sensory event, which acted as a goal to motivate behavior. This demonstrates that dopamine neurons only support ICSS at supraphysiological frequencies, and in a manner that does not reflect our subjective experience with endogenous firing of dopamine neurons during reinforcement learning.One sentence summaryDopamine neurons only support ICSS at supraphysiological frequencies and in a manner not reflecting dopamine’s role in learning.

With the increase in hospital consolidation over the past decade, multiple studies have been performed evaluating patient outcomes after consolidation. To date, there have not been studies performed to assess outcomes in pediatric trauma patients. The goal was to assess pediatric patient outcomes in a children’s hospital after consolidation of two Level 1 Trauma centers in a rural Appalachian health system. A retrospective analysis of data from the Trauma Registry between October 2015 - September 2020 was performed. The variables included in analysis were age, injury severity score (ISS), hospital days, intensive care unit days, ventilator days, mortality, discharge disposition, consults, and hospital visit cost. Despite increased ISS, there was no difference in in-patient outcomes. However, these patients were more likely to require orthopedic evaluation and further outpatient care after discharge, suggesting more severely injured patients were evaluated by the trauma service post consolidation.

Background: A primary goal of anterior cruciate ligament reconstruction (ACLR) is to reduce pathologically increased anterior and rotational laxity of the knee, but the effects of residual laxity on patient-reported outcomes (PROs) after ACLR remain unclear. Hypothesis: Increased residual laxity at 2 years postoperatively is predictive of a higher risk of subsequent ipsilateral knee surgery and decreases in PRO scores from 2 to 6 years after surgery. Study Design: Cohort study; Level of evidence, 2. Methods: From a prospective multicenter cohort, 433 patients aged 6 mm) in laxity at 2 years postoperatively. Multiple linear regression models were built to determine the relationship between 2-year postoperative knee laxity and 2- to 6-year change in PROs while controlling for age, sex, body mass index, smoking status, meniscal and cartilage status, and graft type. Results: A total of 381 patients (87.9%) were available for follow-up 6 years postoperatively. There were no significant differences in risk of subsequent knee surgery based on residual knee laxity. Patients with a difference >6 mm in side-to-side anterior laxity at 2 years postoperatively were noted to have a larger decrease in PROs from 2 to 6 years postoperatively ( P < .05). No significant differences in any PROs were noted among patients with a difference Conclusion: The presence of a residual side-to-side KT-1000 arthrometer difference 6 mm in side-to-side anterior laxity were noted to have significantly decreased PROs at 6 years after ACLR.

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.

Cardiac rehabilitation is a class 1 recommendation for acute coronary syndrome (ACS) patients according to the American College of Cardiology/American Heart Association. However, only 1 in 5 ACS patients are referred for cardiac rehabilitation nationally, and even fewer at our institution. We sought to improve the number of referrals to cardiac rehabilitation for post-ACS patients admitted to our inpatient cardiology service, and ultimately their participation in the program. We designed a quality improvement initiative that included education of patients and house staff, automated referral order, and participation of cardiac rehabilitation staff members on multidisciplinary rounds. We compared the number of patients who received a referral to cardiac rehabilitation, had the first appointment scheduled before hospital discharge, and attended the program before and after our intervention. Six months after initiation of the project, the proportion of ACS patients referred to cardiac rehabilitation before hospital discharge increased from 10% to 43% (P < 0.001). The mean number of patients with a cardiac rehabilitation appointment scheduled before discharge was 2 before and 5 after the intervention (P < 0.001), and the mean number of patients who attended their scheduled appointment was 1 before and 3 after the intervention (P = 0.001). Run charts demonstrated that the number of referrals and the number of scheduled appointments remained above the median following the intervention. In conclusion, an initiative that included education, automated referrals, and direct one-on-one contact with cardiac rehabilitation staff before discharge increased the number of cardiac rehabilitation referrals, and appointments scheduled and attended in post-ACS patients.

It has been proposed that binge eating reflects a pathological compulsion driven by the “addictive” properties of foods. Proponents of this argument highlight the large degree of phenomenological and diagnostic overlap between binge eating disorder (BED) and substance use disorders (SUDs), including loss of control over how much is consumed and repeated unsuccessful attempts to abstain from consumption, as well as commonalities in brain structures involved in food and drug craving. To date, very little attention has been given to an additional behavioral symptom that BED shares with SUDs—sleep dysregulation—and the extent to which this may contribute to the pathophysiology of BED. Here, we review studies examining sleep outcomes in patients with BED, which collectively point to a heightened incidence of sleep abnormalities in BED. We identify the orexin (hypocretin) system as a potential neurobiological link between compulsive eating and sleep dysregulation in BED, and provide a comprehensive update on the evidence linking this system to these processes. Finally, drawing on evidence from the SUD literature indicating that the orexin system exhibits significant plasticity in response to drugs of abuse, we hypothesize that chronic palatable food consumption likewise increases orexin system activity, resulting in dysregulated sleep/wake patterns. Poor sleep, in turn, is predicted to exacerbate binge eating, contributing to a cycle of uncontrolled food consumption. By extension, we suggest that pharmacotherapies normalizing orexin signaling, which are currently being trialed for the treatment of SUDs, might also have utility in the clinical management of BED.

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.

Patellar tendon (PT) and quadriceps tendon (QT) ruptures represent significant injuries and warrant surgical intervention in most patients. Outcome data are predominantly retrospective analyses with low sample sizes. There are also minimal data comparing QT and PT repairs and the variables impacting patient outcomes. The level of evidence of the study is level II (prognosis). From the prospective OME cohort, 189 PT or QT repairs were performed between February 2015 and October 2019. Of these, 178 were successfully enrolled (94.2%) with 1-year follow-up on 141 (79.2%). Baseline demographic data included age, sex, race, BMI, years of education, smoking status, and baseline VR-12 MCS score. Surgical and follow-up data included surgeon volume, fixation technique, baseline, and 1-year Knee Injury and Osteoarthritis Outcome Score-Pain (KOOS-Pain), Knee Injury and Osteoarthritis Outcome Score—Physical Function (KOOS-PS), and 1-year Patient Acceptable Symptom State (PASS) scores and complications. Multivariable regression analysis was utilized to identify prognosis and significant risk factors for outcomes—specifically, whether KOOS-Pain or KOOS-PS were different between QT versus PT repairs. There were 59 patients in the PT cohort and 82 patients in QT cohort. Baseline demographic data demonstrated that PT cohort was younger (45.1 vs. 59.5 years, p

Background: Arthroscopic partial meniscectomy (APM) is widely performed and remains an important therapeutic option for patients with a meniscal tear. However, it is debated whether or not APM accelerates the progression of osteoarthritis (OA) in the long term. Purpose/Hypothesis: The purpose was to compare the progression of OA measured by the change in tibiofemoral joint space width (JSW)—a quantitative measure of OA radiographic severity—across 3 groups with a midterm follow-up: (1) patients undergoing APM; (2) those with a meniscal tear treated nonoperatively; and (3) those without a tear. We hypothesized that the reduction in JSW would be greatest in patients undergoing APM and least in those patients without a tear. Study Design: Cohort study; Level of evidence, 3. Methods: Using the Osteoarthritis Initiative cohort, a total of 144 patients were identified that underwent APM with at least 12 months of follow up and without previous knee surgery. Those with a meniscal tear who did not have APM (n = 144) and those without a tear (n = 144) were matched to patients who had APM by sex, age, Kellgren-Lawrence (KL) grade, and follow up time. Participants underwent magnetic resonance imaging at baseline. Knee radiographs to assess JSW were collected annually or biannually. The change in minimum medial compartment JSW was calculated using a validated automated method. A piecewise linear mixed effects model was constructed to examine the relationship between JSW decline over time and treatment group—adjusting for age, body mass index, smoking status, KL grade, and baseline JSW. Results: All groups had comparable baseline JSW—ranging from 4.33 mm to 4.38 mm. The APM group had a rate of JSW decline of −0.083 mm/mo in the first 12 months and −0.014 mm/mo between 12 and 72 months. The rate of JSW decline in the APM group was approximately 27 times greater in the first 12 months than that in the nonsurgical group (−0.003 mm/mo) and 5 times greater than that in the no tear group (−0.015 mm/mo); however, there was no significant difference between groups for 12 to 72 months (nonsurgical group: −0.009 mm/mo; no tear group: −0.010 mm/mo). The adjusted JSW in the APM group was 4.38 mm at baseline and decreased to 2.57 mm at 72 months; the JSW in the nonsurgical group declined from 4.31 mm to 3.73 mm, and in the no tear group it declined from 4.33 mm to 3.54 mm. There was a statistically significant difference in JSW change between baseline and 72 months for the APM group compared with the other groups ( P < .001), but not between the nonsurgical and no tear groups ( P = .12). Conclusion: In the first postoperative year, APM results in a faster rate of joint space narrowing compared with knees undergoing nonsurgical management of meniscal tears. Thereafter, there are comparable rates of OA progression regardless of the chosen management. APM results in a persistent decrease in JSW over at least 72 months. An untreated meniscal tear does not contribute to radiographic progression—assessed by JSW—as compared with an intact meniscus.

Background: Parents seek support on behalf of their transgender and gender nonconforming (TGNC) children. Previous qualitative studies explore the types of support parents seek inside and outside of healthcare settings. Healthcare providers often remain unprepared to effectively provide gender-affirming services to TGNC children and their accompanying parents and may benefit from learning about the support seeking experiences of parents with TGNC children. Aims: This paper summarized qualitative research studies that address the topic of parents seeking support on behalf of their TGNC children. We produced this report for healthcare providers to review to enhance gender-affirming services for parents and TGNC children. Methods: This paper outlines a qualitative metasummary of studies from the United States or Canada with data collected from parents of TGNC children. Data collection included the steps of journal runs, database searches, reference checks, and area scans. Data analysis involved the steps of extracting, editing, grouping, abstracting, and calculating the intensity and frequency effect sizes for finding statements from qualitative research study articles. Results: The results of this metasummary yielded two primary themes, six subthemes, and 24 total findings. The first primary theme of seeking guidance had three subthemes: educational resources, community networks, and advocacy efforts. The second primary theme of seeking healthcare had three subthemes: healthcare providers, mental healthcare, and general healthcare. Discussion: These findings provide information healthcare providers can use to inform their practice. These findings also highlight the importance of providers working collaboratively with parents when serving TGNC children. This article concludes with practical tips for providers.

Background: The incidence of posttraumatic osteoarthritis (PTOA) based on clinical radiographic grading criteria at 10 years after anterior cruciate ligament (ACL) reconstruction (ACLR) has not been well-defined in a prospective cohort of young athletic patients. Hypothesis: Among young athletic patients, there is a high incidence of clinical radiographic PTOA at 10 years after ACLR. Additionally, there is a significant difference in clinical radiographic osteoarthritis (OA) changes (joint space narrowing and osteophyte formation) between ACL-reconstructed and contralateral knees at 10 years. Study Design: Case series; Level of evidence, 4. Methods: The first 146 patients in an ongoing nested cohort study of the Multicenter Orthopaedic Outcomes Network (MOON) prospective cohort presented for a minimum 10-year follow-up. Included patients had a sports-related ACL injury, were aged Results: Interrater reliability was substantial for the IKDC (Gwet Agreement Coefficient [AC] 1 = 0.71), moderate for the KL (0.48), and almost perfect for the OARSI (0.84) grading systems. Among patients with a contralateral radiographically normal knee, the 10-year incidence of clinical radiographic PTOA after ACLR was 37% as defined by osteophytes and 23% as defined by joint space narrowing. The maximum side-to-side difference in the OARSI osteophyte grade in the medial or lateral compartment was 0 in 65% of patients, 1 in 20%, and ≥2 in 15%. The maximum side-to-side difference in the OARSI joint space narrowing grade was 0 in 77% of patients, 1 in 19%, and ≥2 in 4%. Conclusion: In young active patients, the 10-year incidence of clinical radiographic PTOA after ACLR was 37% as defined by osteophytes and 23% as defined by joint space narrowing. The mean difference in the degree of osteophyte formation (≤1 grade in 85%) and joint space narrowing (≤1 grade in 96%) between the ACL-reconstructed and contralateral knees was small. Registration: NCT02717559 (ClinicalTrials.gov identifier)

Compared to traditional experimental approaches, computational modeling is a promising strategy to efficiently prioritize new candidates with low cost. In this study, we developed a novel data mining and computational modeling workflow proven to be applicable by screening new analgesic opioids. To this end, a large opioid data set was used as the probe to automatically obtain bioassay data from the PubChem portal. There were 114 PubChem bioassays selected to build quantitative structure–activity relationship (QSAR) models based on the testing results across the probe compounds. The compounds tested in each bioassay were used to develop 12 models using the combination of three machine learning approaches and four types of chemical descriptors. The model performance was evaluated by the coefficient of determination (R(2)) obtained from 5-fold cross-validation. In total, 49 models developed for 14 bioassays were selected based on the criteria and were identified to be mainly associated with binding affinities to different opioid receptors. The models for these 14 bioassays were further used to fill data gaps in the probe opioids data set and to predict general drug compounds in the DrugBank data set. This study provides a universal modeling strategy that can take advantage of large public data sets for computer-aided drug design (CADD).