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Hip arthroscopy is increasingly used as a tool for evaluating and managing painful hip in active patients. The complex anatomy of the lower back, abdomen, pelvis, and upper thigh can make the diagnosis challenging. A thorough history and physical examination in addition to specific imaging modalities can verify the presence or absence of various intra-and extra-articular disorders of the hip. Although hip pain in athletes is often managed conservatively, specific disorders and injuries are appropriately and successfully treated with hip arthroscopy. [ABSTRACT FROM AUTHOR]

Treatment failures after screw fixation of Jones fractures are reported to be infrequent. Between 1993 and 1999, 15 patients (mean age, 21.7 years) underwent cannulated screw fixation of a Jones fracture at our institution. There were six treatment failures: four refractures and two symptomatic nonunions. The mean time to full activity was 6.8 weeks for the patients with failure compared with 9 weeks for patients who did not have complications. Although all patients were asymptomatic and radiographically progressing to union before return to full activity, only one of six patients with failures had complete radiographic union, compared with six of seven patients with no complications. There was a higher proportion of elite athletes (division I or professional level) among the failure group (83%) compared with those without complications (11%). There were no significant differences in age, sex, screw diameter, use of bone graft, or age of fracture between patients with failures and those without complications. Return to full activity, especially among elite athletes, before complete radiographic union was predictive of failure. Even though intramedullary screw fixation offers advantages over nonoperative treatment, a significant risk of postoperative complications exists. [ABSTRACT FROM AUTHOR]

Background: Because of the increased prevalence of revision anterior cruciate ligament (ACL) reconstruction, there has been a desire to understand the role of posterior tibial slope on increased anterior tibial translation and increased ACL graft forces. One potential concern in supratubercle anterior closing wedge proximal tibial osteotomy (ACW-PTO) for decreasing the posterior tibial slope is the risk of altering the patellar height., Purpose: To radiographically assess changes in (1) patellar height, (2) anterior tibial translation, and (3) posterior tibial slope after supratubercle ACW-PTO., Study Design: Case series; Level of evidence, 4., Methods: Patients who underwent supratubercle ACW-PTO by a single surgeon between July 2019 and June 2023 were included. Standardized lateral knee weightbearing radiographs to assess patellar height (via the Caton-Deschamps index), anterior tibial translation of the lateral tibial plateau relative to the lateral femoral condyle, and posterior tibial slope were obtained at 4 time points (preoperatively and 1 day, 3 months, and 6 months postoperatively). Paired t test was used to compare differences between preoperative, 1-day, and 3- and 6-month values for patellar height as measured using the Caton-Deschamps index and for posterior tibial slope. Paired t test was also used to compare differences in the preoperative and 6-month postoperative values for anterior tibial translation., Results: In 20 patients after ACW-PTO, the Caton-Deschamps index demonstrated a significant increase in patellar height on postoperative day 1 ( P < .001) but no significant differences at 3 ( P = .057) and 6 ( P = .176) months postoperatively. Anterior tibial translation on standing lateral knee radiographs was significantly decreased by a mean of 8.9 mm from preoperatively to 6 months postoperatively ( P < .001). Posterior tibial slope was significantly decreased by a mean of 11.2° from preoperatively to 6 months postoperatively ( P < .001)., Conclusion: Supratubercle ACW-PTO performed for ACL reconstruction failure in the setting of an increased posterior tibial slope did not induce significant changes in patellar height postoperatively. Furthermore, after ACW-PTO, there was a significant decrease in anterior tibial translation and posterior tibial slope., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: N.I.K. has received support for education from Foundation Medicine and Smith & Nephew and hospitality payments from Zimmer Biomet and Encore Medical. C.A.W. has ownership and investment interest in Responsive Arthroscopy and has received speaking fees from Smith & Nephew. C.M.L. has received speaking fees from Smith & Nephew and Synthes and consulting fees from Smith & Nephew and Responsive Arthroscopy. R.F.L. has received consulting fees from Ossur, Smith & Nephew, and Responsive Arthroscopy; royalties from Ossur, Smith & Nephew, Elsevier, and Arthrex; research support from Ossur and Smith & Nephew; and support for education from Foundation Medicine. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Stress radiography is a viable imaging modality that can also be used to assess the integrity of the anterior cruciate ligament (ACL) after primary or secondary injury. Because conventional radiography is relatively easy, affordable, and available worldwide, the diagnostic efficacy of ACL standing, lateral decubitus, and supine stress radiography should be evaluated., Purpose: To examine the existing literature regarding the application of stress radiography in evaluating the integrity of the ACL., Study Design: Systematic review; Level of evidence, 3., Methods: Using the PubMed and MEDLINE databases for relevant articles published between 1980 and the present, a systematic review was conducted to identify evidence related to the radiographic diagnosis or assessment of ACL tears. The literature search was conducted in September 2022., Results: Of 495 studies, 16 (1823 patients) were included. Four studies examined standing stress radiography, and 12 investigated lateral decubitus or supine stress radiography. Significant heterogeneity in imaging technique and recorded anterior tibial translation was identified. Anterior tibial translation for ACL-injured knees ranged from 1.2 to 10.6 mm for standing stress radiographs and 2.7 to 11.2 mm for supine stress radiographs, with high sensitivities and specificities for both., Conclusion: Stress radiography was a dependable diagnostic method for identifying ACL rupture. Further research is necessary to determine the ideal anatomic landmarks, optimal patient positioning, and appropriate applied stresses to establish a standardized protocol for both assessing ACL tears and evaluating the postoperative integrity of ACL reconstruction using stress radiography., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: C.M.L. has received nonconsulting fees from Smith + Nephew and Synthes GmbH and consulting fees from Responsive Arthroscopy and Smith + Nephew. C.A.W. has received nonconsulting fees from Smith + Nephew. N.I.K. has received education payments from Foundation Medical and Smith + Nephew and hospitality payments from Encore Medical and Zimmer Biomet. R.F.L. has received education payments from Foundation Medical; consulting fees from Smith + Nephew; nonconsulting fees from Smith + Nephew and Linvatec; and royalties from Arthrex and Smith + Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Of the three Food and Drug Administration-approved melanocortin peptide drugs, two possess a cyclic scaffold, demonstrating that cyclized melanocortin peptides have therapeutic relevance. An extracyclic Arg residue, critical for pharmacological activity in the approved melanocortin cyclic drug setmelanotide, has also been demonstrated to increase the signal when fluorescently labeled cell-penetrating cyclic peptides are incubated with HeLa cells, with the maximal signal observed with three extracyclic Arg amino acids. Herein, a branching Lys residue was substituted into two macrocyclic melanocortin peptide agonists to incorporate 0-3 extracyclic Arg amino acids. Incorporation of the Arg residues resulted in equipotent or increased agonist potency at the mouse melanocortin receptors in vitro , suggesting that these substitutions were tolerated in the macrocyclic scaffolds. Further in vivo evaluation of one parent ligand (c[Pro-His-DPhe-Arg-Trp-Dap-Ala-Pro]) and the three Arg derivative (c[Pro-His-DPhe-Arg-Trp-Dap-Lys(Ac-Arg-Arg-Arg)-Pro)] demonstrated that the three Arg derivative further decreased food intake compared to the parent macrocycle when the compounds were administered either via intrathecal injection or subcutaneous dosing. This suggests that three extracyclic Arg amino acids may be beneficial in the design of cyclic melanocortin ligands and that in vitro pharmacological profiling may not predict the in vivo efficacy of melanocortin ligands., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Buprenorphine in an extended-release formulation intended for use in laboratory subjects is frequently administered to rats to provide extended analgesia without repeated handling. While levels of buprenorphine may persist in serum once extended-release buprenorphine has been introduced, exposure to opioids can cause opioid tolerance or opioid-induced hypersensitivity. This work examined the analgesic duration and efficacy of a single administration of extended-release buprenorphine intended for use in laboratory subjects in models of inflammatory pain and post-operative pain and the development of opioid tolerance in rat. After subcutaneous administration of 1 mg/kg extended-release buprenorphine, analgesic efficacy did not persist for the expected 72 hours. No changes were observed in mechanical thresholds in the hindpaws that were contralateral to the injury, suggesting a lack of centrally mediated opioid-induced hypersensitivity. To determine whether opioid tolerance arose acutely after one exposure to extended-release buprenorphine, we conducted the warm water tail flick assay; on Day 1 we administered either saline or extended-release buprenorphine (1 mg/kg) and on Day 3 we quantified the standard buprenorphine dose-response curve (0.1-3 mg/kg). Rats previously given extended-release buprenorphine displayed decreased analgesic responses after administration of standard buprenorphine as compared to the robust efficacy of standard buprenorphine in control subjects. Males appeared to show evidence of acute opioid tolerance, while females previously exposed to opioid did not demonstrate a decreased response at the doses examined. Taken together, these results suggest that opioid tolerance arises quickly in male rats after exposure to the extended-release formulation of buprenorphine. This tolerance may account for the brief period of antinociception observed., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Larson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Stress radiographs are an easily accessible, cost-effective tool in the evaluation of acute and chronic ligament knee injuries. Stress radiographs provide an objective, quantifiable, and functional assessment of the injured ligament and can be a useful adjunct when planning surgical management and to objectively assess postoperative outcomes. This study aimed to review the literature reporting on stress radiographic techniques in evaluating knee ligament injury and instability and propose thresholds for interpreting stress radiography techniques., Methods: The following three databases, OVID MEDLINE, the EMBASE library, and the Cochrane Controlled Trials Register, were systematically searched on January 23, 2023, for studies published from January 1970 to January 2023. The search extended to the reference lists of all relevant studies and orthopedic journals. Included studies were those that described a stress technique for the diagnosis of knee ligament injury; studies that reported a description or comparison of the accuracy and/or reliability of one or several stress radiography techniques, or studies that reported a comparison with alternative diagnostic modalities., Results: Sixteen stress radiography techniques were reported for assessing the ACL with stress applied in the anterior plane, 10 techniques for assessing the PCL with stress applied in the posterior plane, 3 techniques for valgus stress, and 4 techniques for varus stress. The Telos device was the most commonly used stress device in the ACL and PCL studies. There was no consensus on the accuracy and reliability of stress radiography techniques for the diagnosis of any knee ligament injury. Stress radiography techniques were compared with alternative diagnostic techniques including instrumented arthrometry, MRI, and physical examination in 18 studies, with variability in the advantages and disadvantages of stress radiography techniques and alternatives. Analysis of results pooled from different studies demonstrated average delta gapping in knees with a completely injured ligament compared to the normal contralateral knee as per the following: for the ACL 4.9 ± 1.4 mm; PCL 8.1 ± 2.5 mm; MCL 2.3 ± 0.05 mm; and the FCL 3.4 ± 0.2 mm., Conclusion: Despite heterogeneity in the available literature with regard to stress examination techniques and device utilization, the data support that stress radiography techniques were accurate and reliable when compared to numerous alternatives in the diagnosis of acute and chronic knee ligament injuries. The present study also provides average increased ipsilateral compartment gapping/translation for specific knee ligament injuries based on the best available data. These values provide a reference standard for the interpretation of stress radiography techniques, help to guide surgical decision-making, and provide benchmark values for future investigations., Level of Evidence: III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Cam-type femoroacetabular impingement is characterized by a pathologic asphericity of the femoral head-neck junction, and arthroscopic femoral osteoplasty is indicated to correct the bony abnormality and restore normal hip mechanics when symptomatic. Residual femoroacetabular impingement deformity after arthroscopy is a leading cause of failure, and it is therefore critical to perform a thorough fluoroscopic and dynamic assessment when addressing cam deformities arthroscopically. The fluoroscopic assessment uses 6 anteroposterior views, including 3 in hip extension (30° internal rotation, neutral rotation, and 30° external rotation) and 3 in 50° flexion (neutral rotation, 40° external rotation, 60° of external rotation), performed before, during, and after the femoral resection. The dynamic assessment includes evaluation of impingement-free range of motion and "end feel" (a subjective description of the tactile feedback during assessment of hip motion), and should be performed before and after the femoral resection in 3 specific positions (extension/abduction, flexion/abduction, and flexion/internal rotation). Although the anterior aspect of the head-neck junction is readily accessed through standard arthroscopic portals with the hip in 30 to 50° of flexion, the posterolateral, posteromedial, and posterior extent of the femoral head-neck junction are challenging to address. The natural external rotation of the proximal femur during flexion and internal rotation during extension can be used to gain posterior lateral and medial access. Antero/posteromedial femoral access can be obtained with >50° of hip flexion with the burr in the anteromedial portal. Posterolateral femoral access is achieved with hip extension with the burr in the anterolateral portal, and further posterolateral access can be achieved with the addition of traction, allowing resection of posterolateral deformities extending beyond the lateral retinacular vessels while remaining proximal to the vessels. This comprehensive intraoperative fluoroscopic and dynamic assessment and surgical technique can lead to a predictable correction of most cam-type deformities., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Full-thickness acetabular cartilage lesions are common findings during primary surgical treatment of femoroacetabular impingement (FAI)., Purpose: To evaluate clinical outcomes after acetabular microfracture performed during FAI surgery in a prospective, multicenter cohort., Study Design: Cohort Study; Level of evidence, 3., Methods: Patients with FAI who had failed nonoperative management were prospectively enrolled in a multicenter cohort. Preoperative and postoperative (mean follow-up, 4.3 years) patient-reported outcome measures were obtained with a follow-up rate of 81.6% (621/761 hips), including 54 patients who underwent acetabular microfracture. Patient characteristics, radiographic parameters, intraoperative disease severity, and operative procedures were analyzed. Propensity matching using linear regression was used to match 54 hips with microfracture to 162 control hips (1:3) to control for confounding variables. Subanalyses of hips ≤35 and >35 years of age with propensity matching were also performed., Results: Patients who underwent acetabular microfracture were more likely to be male (81.8% vs 40.9%; P < .001), be older in age (35.0 vs 29.9 years; P = .001), have a higher body mass index (27.2 vs 25.0; P = .001), and have a greater alpha angle (69.6° vs 62.3°; P < .001) compared with the nonmicrofracture cohort (n = 533). After propensity matching to control for covariates, patients treated with microfracture displayed no differences in the modified Harris Hip Score or Hip Disability and Osteoarthritis Outcome Score ( P = .22-.95) but were more likely to undergo total hip arthroplasty (THA) (13% [7/54] compared with 4% [6/162] in the control group; P = .002), and age >35 years was associated with conversion to THA after microfracture. Microfracture performed at or before 35 years of age portended good outcomes with no significant risk of conversion to THA at the most recent follow-up., Conclusion: Microfracture of acetabular cartilage defects appears to be safe and associated with reliably improved short- to mid-term results in younger patients; modified expectations should be realized when full-thickness chondral lesions are identified in patients >35 years of age.

Purpose: To determine the prevalence of 4 different types of acetabular rim ossifications, including partial labral ossification or punctate calcification, true os acetabuli, acetabular rim stress fracture, and complete labral ossification, and to determine whether different types of periacetabular ossifications are linked to demographic or radiological factors., Methods: We retrospectively reviewed the medial records of patients presenting for hip-related complaints at 2 sports medicine practices from September 2007 to December 2009. An anteroposterior radiograph of both hips and a lateral radiograph of each hip was obtained for all patients and reviewed for findings of cam and pincer femoroacetabular impingement, degenerative changes (Tönnis grade), and periacetabular calcifications for both hips. These parameters were also evaluated with respect to symptoms, sex, and age., Results: Four hundred ninety-one consecutive patients (982 hips) presented to 2 orthopaedic surgeons at 2 centers for "hip"-related complaints. There were 223 males and 268 females (age 39 ± 14 years). The overall prevalence of periacetabular calcifications in hips was 17.6%, with 56.6% of calcifications in the symptomatic hip and 43.4% in the contralateral hip. Four basic patterns of calcification were identified: punctuate calcifications within the labrum (8.0% hips), large rounded calcifications (os acetabuli) (4.2% hip), large fragments with a vertical line of the superior-lateral acetabular rim, consistent with healed or non-healed stress fracture (2.0% hips), and complete ossification of the labrum (3.4% hips). Overall, male sex ( P  = .002), increased lateral center-edge angle ( P  = .046), and higher Tönnis grade ( P < .001) statistically predicted the presence of periacetabular ossification. Punctate calcifications were more prevalent in males ( P  = .002). Higher Tönnis grade ( P  = .029) and increased alpha angle ( P  = .046) were more prevalent with os acetabuli. Younger age ( P  = .001), male sex ( P  = .048), increased alpha angle ( P  = .012), and increased lateral center-edge angle ( P < .001) were more prevalent in acetabular rim fractures. No factors were statistically significant at predicting the presence of an ossified labrum., Conclusions: Periacetabular calcifications are not uncommon. Four particular patterns of calcification are identified: punctate labral calcifications (8%), larger rounded calcifications (i.e., os acetabuli) (4.2%), acetabular rim stress fractures (2%), and complete ossification of the labrum (3.4%) for a combined prevalence of 17.6% in patients presenting to an orthopaedic surgeon with "hip"-related complaints. Nearly half were in the asymptomatic hip. Male sex had a higher prevalence of periacetabular calcifications. An increased lateral center edge angle and higher Tönnis grade also had a higher prevalence of periacetabular calcifications. Younger male patients are more likely to have acetabular rim stress fractures. Patients with an increased alpha angle have a higher prevalence of os acetabuli and rim stress fractures., Clinical Relevance: This study aims to identify, quantify, and categorize periacetabular calcifications about the hip. Their clinical relationships and relevance have been discussed, but no study has distinctly categorized the various types and their prevalence. This study provides a framework for identification and categorization., (© 2023 Published by Elsevier Inc. on behalf of the Arthroscopy Association of North America.)

Background: Anterior inferior iliac spine (AIIS) impingement has been increasingly recognized as a source of extra-articular impingement and hip pain. However, no aggregate data analysis of patient outcomes after AIIS decompression has been performed., Purpose: To evaluate outcomes after arthroscopic AIIS decompression., Study Design: Meta-analysis; Level of evidence, 4., Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were queried for all English-language studies reporting outcomes of arthroscopic AIIS decompression performed in isolation or in conjunction with hip impingement correction surgery. After screening, 10 articles were included. The indications for AIIS decompression were recorded, and weighted mean improvements in patient-reported outcome (PRO) scores, complication rates, and revision rates were calculated., Results: A total of 547 patients (311 women; 57%) were identified, with a total of 620 operative hips. The mean age was 28.42 ± 5.6 years, and the mean follow-up was 25.22 ± 11.1 months. A total of 529 hips (85%) underwent AIIS decompression, 530 hips (85%) underwent femoral osteochondroplasty, and 458 hips (74%) underwent labral repair. Of the patients, 13% underwent bilateral AIIS decompression. The mean modified Harris Hip Score improved from 61.3 ± 6.9 to 88.7 ± 4.7 postoperatively (change, 27.4 ± 5.7 points; P < .001), the Hip Outcome Score-Activities of Daily Living improved from 67.2 ± 10.6 to 91.1 ± 3.2 postoperatively (change, 24.0 ± 8.0 points; P = .001), and the Hip Outcome Score-Sports Specific Subscale improved from 36.8 ± 19.2 to 82.8 ± 3.8 postoperatively (change, 46.0 ± 18.2 points; P = .002). The pooled risk of postoperative complications was 1.1% (95% CI, 0.1%-2.1%), and the pooled risk of needing revision surgery was 1.0% (95% CI, 0.1%-2.0%). No complication was directly attributed to the AIIS decompression portion of the procedure., Conclusion: PROs improved significantly after hip arthroscopy with AIIS decompression, with a low risk of postoperative complications and subsequent revision surgeries. Failure to identify extra-articular sources of hip pain in outcomes of femoroacetabular impingement syndrome, including from the AIIS, could lead to poorer outcomes and future revision surgery.

Purpose: To evaluate outcomes of hip arthroscopy in patients with global acetabular retroversion and to identify correlations between sex, radiographic measurements, athlete status, and return to play with patient-reported outcomes (PROs)., Methods: Retrospective study of patients with global acetabular retroversion who underwent arthroscopic femoroacetabular impingement (FAI) surgery was performed. Global acetabular retroversion was defined by 3 criteria: the crossover sign, ischial spine sign, and posterior wall sign on an anteroposterior (AP) pelvic radiograph. Radiographs were used to measure lateral center edge angle, alpha angle, and anterior and posterior wall indices. Femoral version was measured with 3-dimensional computed tomography. Demographics included age, gender, athlete status, return to play, and reoperation. PROs included modified Harris Hip Score, Hip Outcome Score (HOS), Hip Disability and Osteoarthritis Outcome Score, visual analog scale (VAS), and Veterans RAND-12. Spearman correlation determined correlation with perioperative PROs. Generalized estimating equation determined independent predictors. Significance was set at P  = .05., Results: From 2013 to 2019, 149 patients (65.0% female) with 160 hips with FAI and global acetabular retroversion underwent hip arthroscopy. Follow-up averaged 29.6 months. All PROs demonstrated significant improvement with the exception of the Veterans RAND-12 Mental. Female patients scored significantly lower on most postoperative PROs and had greater VAS scores ( P  = .0002-0.0402). A greater proportion of male subjects met the minimum clinically important difference for the modified Harris Hip Score (88.00% vs 78.79%) Low femoral version correlated with greater HOS ADL, HOS Sport, and Hip Disability and Osteoarthritis Outcome Score Sport scores ( P  = .0077-0.0177). Athletes reported lower preoperative VAS scores, and higher perioperative scores in multiple PROs ( P  = .0004-0.0486). Nine hips (5.63%) underwent reoperation., Conclusions: Patients with global acetabular retroversion and FAI undergoing hip arthroscopy report good outcomes at short-term follow-up. Male subjects and athletes had superior outcomes compared to female subjects and nonathletes. Radiographic measurements did not correlate with outcomes with exception of low femoral version. Athletes reported lower preoperative pain scores and greater postoperative PROs than nonathletes., Level of Evidence: Level IV, therapeutic case series., (© 2022 The Authors.)

The melanocortin family is involved in many physiological functions, including pigmentation, steroidogenesis, and appetite. The centrally expressed melanocortin-3 and melanocortin-4 receptors (MC3R and MC4R) possess overlapping but distinct roles in energy homeostasis. Herein, the third and fourth positions of a tetrapeptide lead compound [Ac-Arg-Arg-(pI)DPhe-Tic-NH 2 ], previously reported to possess MC3R agonist and MC4R antagonist activities, were substituted with indoylated phenylalanine (Wsf/Wrf) residues in an attempt to generate receptor subtype selective compounds. At the third position, d-amino acids were required for melanocortin agonist activity, while both l- and d-residues resulted in MC4R antagonist activity. These results indicate that l-indoylated phenylalanine residues at the third position of the scaffold can generate MC4R over MC3R selective antagonist ligands, resulting in a substitution pattern that may be exploited for novel MC4R ligands that can be used to probe the in vivo activity of the MC4R without involvement of the MC3R., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Higher postoperative quadriceps function has been positively associated with surgical outcomes after anterior cruciate ligament reconstruction (ACLR). However, the impact of autograft harvest and/or a concomitant meniscal procedure on the recovery of quadriceps strength is not well defined., Purpose: To describe postoperative recovery of quadriceps strength following ACLR related to autograft selection, meniscal status, and sex., Study Design: Retrospective Cohort., Methods: One hundred and twenty-five participants who underwent ACLR with either a hamstring tendon (HT), bone-patellar tendon-bone (BPTB) or quadriceps tendon (QT) autograft were included. At postoperative months 3, 6 and 9, each participant completed an isometric quadriceps strength testing protocol at 90-degrees of knee flexion. Participants' quadriceps average peak torque (Q-AvgPKT), average peak torque relative to body weight (Q-RPKT), and calculated limb symmetry index (Q-LSI) were collected and used for data analysis. Patients were placed in groups based on sex, graft type, and whether they had a concomitant meniscal procedure at the time of ACLR. At each time point, One-way ANOVAs, independent samples t-test and chi-square analyses were used to test for any between-group differences in strength outcomes., Results: At three months after ACLR, Q-RPKT was significantly higher in those with the HT compared to the QT. At all time points, males had significantly greater Q-RPKT than females and HT Q-LSI was significantly higher than BPTB and QT. A concomitant meniscal procedure at the time of ACLR did not significantly affect Q-LSI or Q-RPKT at any testing point., Conclusion: This study provides outcomes that are procedure specific as well as highlights the objective progression of quadriceps strength after ACLR. This information may help better-define the normal recovery of function, as well as guide rehabilitation strategies after ACLR., Level of Evidence: 3., Competing Interests: The authors report no conflicts of interest.

Background: Short- and midterm follow-up studies suggest that arthroscopic labral refixation/preservation leads to superior outcomes compared with labral excision/debridement., Purpose: To update the previous early (16 months) and midterm (mean, 42 months) follow-up of this cohort, which reported better patient-reported outcome measures and lower failure rates in the repair/refixation group., Study Design: Cohort study; Level of evidence, 3., Methods: The authors identified patients who underwent labral debridement/focal labral excision during a period before the development of labral repair techniques. A consecutive group of patients within the labral debridement group thought to be repairable with the authors' current arthroscopic techniques were compared with a group of consecutive patients who underwent labral repair/refixation. In 46 hips, the labrum was focally excised/debrided consistent with pincer- or combined pincer- and cam-type impingement; in 54 hips, the labrum was repaired/refixed. Subjective outcomes were measured with the modified Harris Hip Score (mHHS), 12-Item Short Form Health Survey (SF-12), and visual analog scale (VAS) for pain preoperatively and postoperatively., Results: The mean age was 34.0 years in the debridement group and 28.3 years in the repair/refixation group, with a mean follow-up of 7.3 years (range, 2-13.6 years). At the mean follow-up of 7.3 years, subjective outcomes were significantly improved ( P < .01) for both groups compared with preoperative scores. The mHHS ( P = .008), SF-12 score ( P = .012), and VAS pain score ( P = .002) were all significantly better for the repair/refixation group compared with the debridement group. Although most recent outcomes for both groups fell slightly at the mean follow-up of 7.3 years in comparison with the 16-month and 3.5-year follow-ups, these differences were not significant. However, the failure rate in the debridement group did get significantly worse ( P = .014). Good to excellent results were 47.7% in the debridement group and 86.3% in the refixation group ( P < .001), and failure rates were 30.4% (debridement) and 13% (refixation) ( P = .033). There were 4 revisions in the debridement group and 3 revisions in the refixation group., Conclusion: Longer term, >7-year follow-up comparing focal labral excision/debridement with repair/refixation revealed better patient-reported outcomes and lower failure rates in the labral repair/refixation cohort. Additionally, despite an absolute decrease in patient-related outcome scoring and number of good/excellent results in both groups compared with the 3.5-year report, there was a significantly greater increase in failure rates over time for the excision/debridement group with better maintenance of good to excellent results in the repair/refixation group.

The melanocortin-4 receptor (MC4R) plays an important role in appetite. Agonist ligands that stimulate the MC4R decrease appetite, while antagonist compounds increase food consumption. Herein, a functional mixture-based positional scan identified novel MC4R antagonist sequences. Mixtures comprising a library of 12,960,000 tetrapeptides were screened in the presence and absence of the NDP-MSH agonist. These results led to the synthesis of 48 individual tetrapeptides, of which 40 were screened for functional activity at the melanocortin receptors. Thirteen compounds were found to possess nanomolar antagonist potency at the MC4R, with the general tetrapeptide sequence Ac-Aromatic-Basic-Aromatic-Basic-NH 2 . The most notable results include the identification of tetrapeptide 48 [ COR1-25 , Ac-DPhe(pI)-Arg-Nal(2')-Arg-NH 2 ], an equipotent MC4R antagonist to agouti-related protein [AGRP(86-132)], more potent than miniAGRP(87-120), and possessing 15-fold selectivity for the MC4R versus the MC3R. These tetrapeptides may serve as leads for novel appetite-inducing therapies to treat states of negative energy balance, such as cachexia and anorexia.

Objectives: To evaluate the self-reported incidence of sleep disturbances, defined as ≤7 hours of sleep per 24-hour period, in patients undergoing arthroscopic-assisted knee surgery., Methods: Patients who underwent arthroscopic knee surgery over the course of a 4-month period were prospectively included. Patients were excluded if a history of insomnia or other sleep altering medical history was reported. Self-reported sleep metrics included average number of hours of sleep per night, average number of awakenings during sleep per night, perceived quality of sleep, average pain level during sleep and number of hours of physical activity/therapy per week. Data were collected at weeks 1, 3, and 6 postoperatively. Joint circumference was measured on postoperative day 1 and served as an indicator of a knee effusion. Paired t -tests were used to compare preoperative to postoperative hours of sleep. Simple and multiple linear regression were used to evaluate relationships between surgical variables and postoperative sleep metrics., Results: There were 123 patients who underwent arthroscopic knee surgery during the prospective enrolment period; 83 patients were included in the final analysis. The overall incidence of preoperative sleep disturbances was 20% (n=17). The overall incidence of self-reported postoperative sleep disturbances was 99%, 96% and 90% at weeks 1, 3 and 6, respectively. The average number of hours slept was significantly reduced at 1, 3 and 6 weeks postoperatively compared with the preinjury state (p<0.001). Knee joint circumference had a significantly negative correlation with average number of hours of sleep in the first 6 weeks postoperatively ( R =-0.704; p=0.001). Surgical variables including severity of surgery, weekly postoperative pain level and weekly hours of postoperative physical therapy were not significant independent predictors of acute postoperative sleep disturbances (p>0.05)., Conclusion: Sleep disturbances were commonly reported in patients following arthroscopic knee surgery without correction of sleep metrics by 6 weeks postoperatively. The majority of sleep disturbances in this cohort correlated with an increased knee effusion. A multidisciplinary team approach is recommended to counsel patients regarding the potential for and problems with acute sleep disturbances following arthroscopic knee surgery. Level of evidence : 3., Competing Interests: Competing interests: None declared., (© International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiligament knee injuries (MLKIs) can result from high-energy injury mechanisms such as motor vehicle accidents or low-energy injury mechanisms such as activities of daily living or sports., Purpose/hypothesis: The purpose was to conduct a systematic review on postoperative patient-reported outcomes after MLKIs and to conduct a meta-analysis of comparable outcome variables based upon high- versus low-energy injury mechanisms. It was hypothesized that MLKIs with low-energy injury mechanisms would demonstrate significantly improved subjective clinical outcome scores compared with high-energy injuries., Study Design: Meta-analysis and systematic review., Methods: A systematic review was performed with the inclusion criteria of postoperative MLKI outcomes based upon high-versus low-energy mechanisms of injury with a minimum 2-year follow-up. Outcome scores included were the Lysholm knee scoring scale, Tegner activity scale, and the International Knee Documentation Committee (IKDC) score. High-energy mechanisms included motor vehicle accidents or falls from a height >5 feet; low-energy mechanisms included sports-related injuries, activities of daily living, or falls from <5 feet. A meta-analysis was performed comparing the outcome scores of high- versus low-energy mechanisms of MLKIs., Results: Overall, 1214 studies were identified, 15 of which were included in the systematic review and meta-analysis. Thirteen studies included surgical reconstructions of all injured ligaments. A total of 641 patients with 275 high-energy and 366 low-energy injuries were grouped for comparison in the meta-analysis. No significant differences in Lysholm scale (78.6 vs 78.0) or IKDC scores (69.0 vs 68.4) were found between high- and low-energy groups at a minimum of 2 years (range, 2-10 years) postoperatively ( P > .05). The low-energy injury group demonstrated significantly higher Tegner activity scale scores (5.0 vs 3.9; P = .03). There was no significant difference in failure rates between groups (3.5% vs 2.0%; P = .23)., Conclusion: We found in this systematic review and meta-analysis that patients with low-energy mechanisms of MLKI surgery had improved postoperative Tegner activity scores compared with those patients with high-energy mechanisms after MLKI surgery. However, there were no differences in Lysholm score, IKDC score, or failure rates between high- and low-energy MLKI patients at an average of 5.3 years postoperatively.

Improved understanding of the biomechanical significance and clinical repercussions of tibial slope on cruciate ligament function has sparked a newfound clinical interest in this morphological feature. Using either magnetic resonance imaging or lateral tibia radiographs, the anterior-posterior angulation of the tibial plateau relative to the tibial shaft can be measured. Clinical and biomechanical studies have reported that increased posterior tibial slope (PTS) places significantly increased tension on the native and reconstructed anterior cruciate ligament (ACL), leading to an increased risk of failure. It has also been suggested that increased PTS of the lateral tibial plateau has a greater impact on ACL forces and anterior tibial translation than PTS of the medial tibial plateau. Conversely, a decreased PTS has been shown to be a risk factor for recurvatum deformity, posterior cruciate ligament (PCL) injury, and posterior tibial translation and has been linked to single bundle PCL reconstruction failure. In the setting of ACL insufficiency with a PTS greater than 12°, anterior closing wedge osteotomy has been shown to be protective for ACL reconstructions. Alternatively, some surgeons have advocated for the addition of lateral extraarticular stabilization procedures in the setting of increased PTS. Further, in the setting of PCL insufficiency with an anteriorly directed, or flat, PTS, anterior opening wedge osteotomy has shown encouraging results. In addition, double bundle PCL reconstructions should be strongly considered in the setting of anteriorly directed, or flat, tibial slope., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: To perform a systematic review of reported terminologies, surgical techniques, preoperative diagnostic measures, and geographic differences in the treatment of core muscle injury (CMI)/athletic pubalgia/inguinal disruption., Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify clinical studies or articles that described a surgical technique to treat CMI refractory to nonoperative treatment. The search phrase used was "core muscle injury" OR "sports hernia" OR "athletic pubalgia" OR "inguinal disruption." The diagnostic terminology, country of publication, preoperative diagnostic measures, surgical technique, and subspecialty of the operating surgeons described in each article were extracted and reported., Results: Thirty-one studies met the inclusion and exclusion criteria, including 3 surgical technique articles and 28 clinical articles (2 Level I evidence, 1 Level II, 4 Level III, and 21 Level IV). A total of 1,571 patients were included. The most common terminology used to describe the diagnosis was "athletic pubalgia," followed by "sports hernia." Plain radiographs and magnetic resonance imaging of the pelvis were the most common imaging modalities used in the preoperative evaluation of CMI/athletic pubalgia/inguinal disruption. Tenderness-to-palpation testing was the most common technique performed during physical examination, although the specific locations assessed with this technique varied substantially. The operating surgeons were general surgeons (16 articles), a combination of orthopaedic and general surgeons (7 articles), or orthopaedic surgeons (5 articles). The most common procedures performed were open or laparoscopic mesh repair, adductor tenotomy, primary tissue (hernia) repair, and rectus abdominis repair. The procedures performed differed on the basis of surgeon subspecialty, geographic location, and year of publication., Conclusions: A variety of diagnostic methods and surgical procedures have been used in the treatment of a CMI/athletic pubalgia/sports hernia/inguinal disruption. These procedures are performed by orthopaedic and/or general surgeons, with the procedures performed differing on the basis of surgeon subspecialty and geographic location., Level of Evidence: Level V, systematic review of Level I to V studies., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Over the past 20 years, insights from human and mouse genetics have illuminated the central role of the brain leptin-melanocortin pathway in controlling mammalian food intake, with genetic disruption resulting in extreme obesity, and more subtle polymorphic variations influencing the population distribution of body weight. At the end of 2020, the U.S. Food and Drug Administration (FDA) approved setmelanotide, a melanocortin 4 receptor agonist, for use in individuals with severe obesity due to either pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency., Scope of Review: Herein, we chart the melanocortin pathway's history, explore its pharmacology, genetics, and physiology, and describe how a neuropeptidergic circuit became an important druggable obesity target., Major Conclusions: Unravelling the genetics of the subset of severe obesity has revealed the importance of the melanocortin pathway in appetitive control; coupling this with studying the molecular pharmacology of compounds that bind melanocortin receptors has brought a new obesity drug to the market. This process provides a drug discovery template for complex disorders, which for setmelanotide took 25 years to transform from a single gene into an approved drug., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Femoroacetabular impingement (FAI) can lead to acetabular impaction, chondral injury, and labral pathology secondary to deformities of the proximal femur (CAM-type FAI), acetabulum (pincer-type FAI), or with combined FAI. While the majority of cases are of the combined type, this paper focuses on acetabular overcoverage/pincer-type deformities. Various pincer subtypes include focal anterior overcoverage, global retroversion, global overcoverage/profunda, protrusio, subspine impingement, and os acetabuli/rim fracture variants. A thorough history and physical examination, plain radiographs, magnetic resonance imaging, 3-dimensional computerized tomography, and diagnostic injections can lead to an accurate assessment of pincer-type variants. Appropriately indicated arthroscopic management techniques and pearls for the various pincer subtypes can lead to improved patient-related outcome measures and a high rate of return to athletic activity for the majority of these patients., Competing Interests: Disclosure: R.F.L.: American Journal of Sports Medicine: editorial or governing board. American Orthopaedic Society for Sports Medicine: board or committee member. Arthrex Inc.: IP royalties; paid consultant; research support. International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine: board or committee member. Journal of Experimental Orthopaedics: editorial or governing board. Knee Surgery, Sports Traumatology, Arthroscopy: editorial or governing board. Linvatec: research support. Ossur: IP royalties; paid consultant; research support. Smith & Nephew: IP royalties; paid consultant; research support. C.M.L.: Smith & Nephew: paid consultant. A.B.: American Orthopaedic Society for Sports Medicine: board or committee member. Arthrex Inc.: IP royalties; paid consultant. SLACK Incorporated: publishing royalties, financial, or material support. Springer: publishing royalties. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

There has been an increased emphasis on capsular management during hip arthroscopy in the literature in recent years. The capsule plays a significant role in the hip joint stability and studies have demonstrated that capsular closure can restore the biomechanics of the hip back to the native state. Capsular management also affects functional outcomes with capsular repair resulting in better clinical outcomes in some studies. Management of the capsule has evolved in recent years with more surgeons performing routine capsular closure. Management techniques and degree of capsular closure, however, can be quite variable between surgeons. This review will discuss hip capsular anatomy, the importance of the capsule in hip biomechanics, management of the capsule during arthroscopy, and functional outcomes as it relates to the various capsular closure techniques versus leaving the capsulotomy unrepaired., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Borderline acetabular dysplasia represents a "transitional acetabular coverage" pattern between more classic acetabular dysplasia and normal acetabular coverage. Borderline dysplasia is typically defined as a lateral center-edge angle of 20 to 25 degrees. This definition of borderline dysplasia identifies a relatively narrow range of lateral acetabular coverage patterns, but anterior and posterior coverage patterns are highly variable and require careful assessment radiographically, in addition to other patient factors. Treatment decisions between isolated hip arthroscopy (addressing labral pathology, femoroacetabular impingement bony morphology, and capsular laxity) and periacetabular osteotomy (improving osseous joint stability; often combined with hip arthroscopy) remain challenging because the fundamental mechanical diagnosis (instability vs. femoroacetabular impingement) can be difficult to determine clinically. Treatment with either isolated hip arthroscopy or periacetabular osteotomy (with or without arthroscopy) appears to result in improvements in patient-reported outcomes in many patients, but with up to 40% with suboptimal outcomes. A patient-specific approach to decision-making that includes a comprehensive patient and imaging evaluation is likely required to achieve optimal outcomes., Competing Interests: Disclosure: J.J.N. is a consultant and received research support from Smith and Nephew; is a consultant and received royalties from Responsive Arthroscopy; received research support from Zimmer-Biomet, Stryker, and Department of Defense. C.M.L. is a paid consultant at Smith and Nephew. L.M.F. declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Athletic hip injuries account for a substantial portion of missed time from sports in high-level athletes. For both femoroacetabular impingement (FAI) and core muscles injuries, a thorough history and physical examination are paramount to guide the treatment. While advanced imaging including computed tomography and magnetic resonance imaging are frequently obtained, a wealth of information can be ascertained from standard radiographs alone. For patients with isolated or combined FAI and core muscle injuries (CMIs), the initial treatment is often nonoperative and consists of rest, activity modification, and physical therapy of the hips, core, and trunk. Injections may then aid in both confirming diagnosis and temporary symptom abatement. Arthroscopic procedures for refractory FAI in experienced hands have been shown to be both safe and efficacious. While surgical repair options for CMIs are significantly more variable, long-term studies have demonstrated the rapid resolution of symptoms and high return to play rates. More recently, anatomic and clinical correlations between FAI and CMIs have been identified. Special attention must be paid to elite athletes as the incidence of concurrent FAI with CMI is extremely high yet with significant symptom variability. Predictable return to play in athletes with coexisting symptomatic intra-articular and extra-articular symptomatology is incumbent upon the treatment of both pathologies., Competing Interests: Disclosure: T.S.L. is a paid consultant to Conmed Linvatec and Smith & Nephew. C.M.L. is a paid consultant to Smith & Nephew. J.W.T.B. is a paid consultant and receives royalties from Smith & Nephew and receives royalties from Springer. A.S.P. declares no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Hip arthroscopy techniques have evolved to treat a wide range of extra-articular pathologies. Subspine impingement commonly occurs in femoroacetabular impingement, particularly in athletes with a high range of motion, patients with low degrees of femoral version, and those with large subspine deformities. A reliable technique that preserves the hip capsule would be helpful for hip arthroscopy surgeons. This note details our technique using pericapsular windows proximal to the interportal capsulotomy to access and decompress a subspine deformity in the setting of hip femoroacetabular impingement., (© 2020 by the Arthroscopy Association of North America. Published by Elsevier.)

Purpose: To compare posterior tibial slope (PTS) measurements from standard lateral knee radiographs with measurements from full-length lateral tibia radiographs., Methods: We performed a multicenter, prospective study. Lateral knee and full-length lateral tibia radiographs were obtained for each patient, and PTS was measured. Slope measurements were obtained by measuring the angle between an average of the medial and lateral tibial plateaus and a representative tibial diaphysis line. The proximal anatomic axis was measured on lateral knee radiographs, and both the mechanical axis and anatomic axis were measured on full-length lateral tibia radiographs. The mechanical axis was defined as the center of the plateau to the center of the plafond, and the anatomic axis was defined as the center of the tibial diaphysis. The minimal clinically significant difference was defined a priori as 2° of PTS or greater., Results: A total of 140 patients met the inclusion criteria. The average PTS using the proximal anatomic axis was 11.6° ± 3.2° on lateral knee radiographs; the PTS measured on full-length lateral tibia radiographs was 9.5° ± 3.4° using the mechanical axis and 11.8° ± 3.1° using the anatomic axis. There was a significant difference between the measurements with the mechanical axis and both anatomic axis measurements (P < .01) but no significant difference between the 2 anatomic axis measurement techniques (P = .574). In total, 55% of patients (n = 77) had a 2° or greater difference between the proximal anatomic axis and mechanical axis PTS measurement techniques., Conclusions: There was no significant difference between PTS measurements that used the proximal anatomic axis from lateral knee radiographs and those that used the anatomic axis from full-length lateral tibia radiographs. Thus, lateral knee radiographs are adequate to accurately obtain tibial slope measurements. However, there was a significant difference between PTS measurements that used the anatomic axis and those that used the mechanical axis of the tibia., Clinical Relevance: It is recommended that future studies report tibial slope based upon measurements that utilize the anatomic axis in order to ensure that subsequent conclusions are comparable, independent of the radiographic view., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The five melanocortin receptors regulate numerous physiological functions. Although many ligands have been developed for the melanocortin-4 receptor (MC4R), the melanocortin-3 receptor (MC3R) has been less-well characterized, in part due to the lack of potent, selective tool compounds. Previously an Ac-His-Arg-(pI)DPhe-Tic-NH 2 scaffold, inverting the Phe-Arg motif of the native melanocortin signal sequence, was identified to possess mMC3R over mMC4R selective agonist activity. In this study, a library of 12 compounds derived from this scaffold was synthesized and assayed at the mouse melanocortin receptors (MCRs), utilizing substitutions previously shown to increase mMC3R agonist potency and/or selectivity. One compound ( 8 , Ac-Val-Gln-DBip-DTic-NH 2 ) was identified as greater than 140-fold selective for the mMC3R over the mMC4R, possessed 70 nM potency at the mMC3R, and partially stimulated the mMC4R at 100 μM concentrations without antagonist activity. This pharmacological profile may be useful in developing new tool and therapeutic ligands that selective signal through the MC3R., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Background: Surgical treatment of femoroacetabular impingement (FAI) continues to evolve and is most commonly approached with either hip arthroscopy (HA) or surgical dislocation (SD) of the hip. The purpose of this study was to compare the outcomes of similar patients undergoing surgical treatment of FAI with either HA or SD., Methods: A prospective multicenter cohort study of patients undergoing primary surgical treatment of FAI was performed. Follow-up at a minimum of 1 year (mean, 4.3 years) was available for 621 hips (81.7%), including 399 procedures with HA and 222 procedures with SD. Propensity scores were calculated and reflect the likelihood of surgical treatment with HA versus SD for a given set of covariates. Propensity scores allowed 1:1 matching to identify similar patients at baseline. After propensity matching, 128 matched pairs of patients who underwent HA and 128 matched pairs of those who underwent SD were included in the study. The primary outcome was the postoperative modified Harris hip score (mHHS); secondary outcomes included the Hip disability and Osteoarthritis Outcome Score (HOOS), the University of California Los Angeles (UCLA) activity score, and the Short Form-12 (SF-12) physical and mental subscores, as well as the rate of persistent symptoms, revision surgery, and total hip arthroplasty (THA)., Results: After propensity matching, the 2 groups exhibited similar distributions of all of the covariates that were included in the model. Both groups demonstrated significant improvements in all patient-reported outcomes (PROs). The final mHHS was not significantly different between the 2 matched groups (81.3 for the HA group versus 80.2 for the SD group, p = 0.67). Likewise, the HOOS pain subscale was similar at the time of final follow-up (77.6 versus 80.5, respectively, p = 0.32). No difference between the HA group and the SD group was identified in the rate of THA (0% and 3.1%, respectively, p = 0.41) and revision surgery (7.8% and 10.9%, respectively, p = 0.35); overall rates of persistent symptoms were 21.9% for the HA group and 24.4% for the SD group (p = 0.55)., Conclusions: In a propensity-matched analysis of patients who were treated with either approach, patients undergoing HA or SD demonstrated similar outcomes at a mean of 4 years postoperatively., Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Sustained-release buprenorphine is widely used in mice with the intention of providing long-lasting analgesia. Statements about duration of therapeutic efficacy are based on persistence of serum buprenorphine levels over a minimum threshold, but behavioral data demonstrating sustained efficacy is not established. Additionally, chronic opioid exposure can induce tolerance and/or hyperalgesia; mice receiving sustained-release buprenorphine have not been evaluated for these effects. This study assessed clinical efficacy and duration of sustained-release buprenorphine in inflammatory, post-operative, and cancer pain; and screened for centrally-mediated opioid-induced hyperalgesia as well as opioid tolerance. At 1-2 mg/kg sustained-release buprenorphine, statistically significant analgesic efficacy occurred only at time points up to 2 h. These animals showed no changes in von Frey thresholds on the contralateral side, i.e. no centrally-mediated opioid hyperalgesia. To establish whether acute onset opioid tolerance resulted from a single sustained-release buprenorphine administration, we used the tail flick assay, exposing mice to sustained-release buprenorphine or saline on Day 1 and buprenorphine on Day 2. We measured duration and efficacy of 1 mg/kg buprenorphine after 1 mg/kg sustained-release buprenorphine, and also quantified a dose-response curve of buprenorphine (0.1-3 mg/kg) after 2 mg/kg sustained-release buprenorphine. Compared to control animals, mice previously exposed to sustained-release buprenorphine showed diminished analgesic response to buprenorphine; the resultant dose-response curve showed decreased efficacy. Pretreatment with naloxone, an opioid receptor antagonist, blocked sustained-release buprenorphine analgesic action. The short duration of antinociception following administration of sustained-release buprenorphine in mice is caused by the rapid development of tolerance., (Copyright © 2020. Published by Elsevier B.V.)