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Study questionDoes repeat-associated non-AUG (RAN) translation play a role in fragile X-associated primary ovarian insufficiency (FXPOI), leading to the presence of polyglycine containing protein (FMRpolyG)-positive inclusions in ovarian tissue?Summary answerOvaries of a woman with FXPOI and of an Fmr1 premutation (PM) mouse model (exCGG-KI) contain intranuclear inclusions that stain positive for both FMRpolyG and ubiquitin.What is known alreadyWomen who carry the FMR1 PM are at 20-fold increased risk to develop primary ovarian insufficiency (FXPOI). A toxic RNA gain-of-function has been suggested as the underlying mechanism since the PM results in increased levels of mRNA containing an expanded repeat, but reduced protein levels of fragile X mental retardation protein (FMRP). Recently, RAN translation has been shown to occur from FMR1 mRNA that contains PM repeat expansions, leading to FMRpolyG inclusions in brain and non-CNS tissues of fragile X-associated tremor/ataxia syndrome (FXTAS) patients.Study design, size, durationOvaries of a woman with FXPOI and women without PM (controls), and ovaries from wild-type and exCGG-KI mice were analyzed by immunohistochemistry for the presence of inclusions that stained for ubiquitin and FMRpolyG . The ovaries from wild-type and exCGG-KI mice were further characterized for the number of follicles, Fmr1 mRNA levels and FMRP protein expression. The presence of inclusions was also analyzed in pituitaries of a man with FXTAS and the exCGG-KI mice.Participants/materials, setting, methodsHuman ovaries from a woman with FXPOI and two control subjects and pituitaries from a man with FXTAS and a control subjects were fixed in 4% formalin. Ovaries and pituitaries of wild-type and exCGG mice were fixed in Bouin's fluid or 4% paraformaldehyde. Immunohistochemistry was performed on the human and mouse samples using FMRpolyG, ubiquitin and Fmrp antibodies. Fmr1 mRNA and protein expression were determined in mouse ovaries by quantitative RT-PCR and Western blot analysis. Follicle numbers in mouse ovaries were determined in serial sections by microscopy.Main results and the role of chanceFMRpolyG-positive inclusions were present in ovarian stromal cells of a woman with FXPOI but not in the ovaries of control subjects. The FMRpolyG-positive inclusions colocalized with ubiquitin-positive inclusions. Similar inclusions were also observed in the pituitary of a man with FXTAS but not in control subjects. Similarly, ovaries of 40-week-old exCGG-KI mice, but not wild-type mice, contained numerous inclusions in the stromal cells that stained for both FMRpolyG- and ubiquitin, while the ovaries of 20-week-old exCGG-KI contained fewer inclusions. At 40 weeks ovarian Fmr1 mRNA expression was increased by 5-fold in exCGG-KI mice compared with wild-type mice, while Fmrp expression was reduced by 2-fold. With respect to ovarian function in exCGG-KI mice: (i) although the number of healthy growing follicles did not differ between wild-type and exCGG-KI mice, the number of atretic large antral follicles was increased by nearly 9-fold in 40-week old exCGG-KI mice (P < 0.001); (ii) at 40 weeks of age only 50% of exCGG-KI mice had recent ovulations compared with 89% in wild-type mice (P = 0.07) and (iii) those exCGG-KI mice with recent ovulations tended to have a reduced number of fresh corpora lutea (4.8 ± 1.74 versus 8.50 ± 0.98, exCGG-KI versus wild-type mice, respectively, P = 0.07).Limitations, reasons for cautionAlthough FMRpolyG-positive inclusions were detected in ovaries of both a woman with FXPOI and a mouse model of the FMR1 PM, we only analyzed one ovary from a FXPOI subject. Caution is needed to extrapolate these results to all women with the FMR1 PM. Furthermore, the functional consequence of FMRpolyG-positive inclusions in the ovaries for reproduction remains to be determined.Wider implications of the findingsOur results suggest that a dysfunctional hypothalamic-pituitary-gonadal-axis may contribute to FXPOI in FMR1 PM carriers.Study funding/competing interestsThis study was supported by grants from NFXF, ZonMW, the Netherlands Brain Foundation and NIH. The authors have no conflict of interest to declare.

Risk factors for revision surgery and hospitalization following rotator cuff repair (RCR) have not been clearly identified. We hypothesized patient factors and surgeon and hospital volume independently contribute to the risk of readmission within 90 days and revision RCR within one year. Using the SPARCS database, we included patients undergoing primary RCR in New York State between 1997 and 2002. These patients were tracked for readmission within 90 days and revision RCR within 1 year. A generalized estimating equation was developed to determine whether patient factors, surgeon volume, or hospital volume were independent risk factors for the above outcome measures. The total annual number of RCR increased from 6,656 in 1997 to 10,128 in 2002. Ambulatory cases increased from 57% to 82% during this time period. Independent risk factors for readmission within 90 days included increasing age and increased number of comorbidities. Independent risk factors for revision RCR included increasing age, increased comorbidity, and lower surgeon volume. Hospital volume had a minimal effect on either outcome measure. The shift toward out-patient surgery mirrors the shift from open to arthroscopic rotator cuff repair. The finding that surgeon volume is a predictor of revision RCR reflects the findings in other orthopaedic procedures. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is primarily due to a repeat expansion mutation found in the FMR1 X-linked gene. We have conducted a qualitative analysis of responses from women concerning their attitudes toward testing for carrier status of the fragile X mutation among reproductive-age women. We obtained responses from focus groups including women with and without FXS in their families. We found the following themes: (1) mothers of children with FXS have difficulty formulating their opinions on population screening because of their unique experiences surrounding their own carrier diagnosis and their relationship with their children with FXS, (2) the motivation for carrier testing and need for information differ by family history of FXS and parental status, and (3) the timing of carrier testing with respect to a woman's life stage dictates whether carrier information will be viewed as beneficial or detrimental. There was evidence that non-carrier women from the general population would be wholly unprepared for positive carrier results. These findings have significant implications for genetic counseling as well as for population screening. [ABSTRACT FROM AUTHOR]

The lack of adequate minority representation, including Native-Americans (NA) and African-Americans (AA), in health related research is well documented. Nowhere is this truer than in the area of venomics-related research, which is especially troubling as NA and AA have some of the highest rates of overall morbidity and mortality due to genetic diseases. Objectives: The purpose of this study is to explore factors associated with the under representation of NAandAAadults in genetic research including: (1) decision barriers, (2) the influence of health care networks, (3) recruitment preferences, and (4) health conditions. Methods: Eight focus groups were conducted, each by led by individuals who shared racial/cultural identiflcation with participants. Adherence to tenants of Community Based Participatory Research (CBPR) was maintained. Qualitative data were analyzed using NVIVO program analyses and the constant comparative method. Results: Themes supported the efflcacy of CBPR to help demolish barriers while facilitating a willingness to participate in geneticsrelated research. Conclusions: Community-based approaches may enhance representation of minorities in genomics-related research crucial to eliminating health disparities. [ABSTRACT FROM AUTHOR]

Purpose of Review: The tibial tubercle osteotomy (TTO) is a versatile surgical technique used to treat a range of patellofemoral disorders, including patellar instability, painful malalignment, focal chondral defects, and patellar maltracking that have failed conservative therapies. TTO is a personalized procedure that can be tailored to the pathoanatomy of the patient based on physical examination and imaging. The complication rate associated with TTO strongly depends on the indication for surgery, the severity of the patient's condition, and the surgical approach. Despite the literature on TTO, to our knowledge, no single source has addressed the indications, techniques, outcomes, and complications of this procedure. The purpose of this article is to serve as such a valuable resource., Recent Findings: Highlights from recent studies we would like to emphasize are two-fold. First, maintaining a distal cortical hinge yields lower complication rates than osteotomies involving complete tubercle detachment with classic or standard techniques. Second, based on current evidence, TTO consistently provides symptomatic relief, and most patients can return to work or sport at their pre-operative level within 3 and 6 months, respectively. TTO is a personalizable surgical technique that may be utilized for multiple patellofemoral disorders and is associated with good outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To survey the ACL study group (ACLSG) members to determine the current practice patterns surrounding the use and methodology of lateral extra-articular procedures (LEAPs), including anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET) during ACL reconstruction (ACLR)., Methods: A web-based questionnaire was distributed to members of the ACLSG during the 2016, 2018, 2020, and 2023 biennial meetings. Questions explored the indications and techniques when incorporating LEAPs in ACLR., Results: Analysis of survey responses found that the reported use of LEAPs in both primary and revision ACLR significantly increased between 2016 and 2023 and that surgeons were using lateral augmentation more frequently over time. Surgical techniques were stable across survey years, with most surgeons using iliotibial band (ITB) autograft attached at Gerdy's tubercle, passed under the lateral collateral ligament (LCL), and anchored proximal/posterior to the lateral femoral epicondyle., Conclusion: Survey responses demonstrate that LEAPs are becoming more common among ACL surgeons in the ACL SG, with the modified Lemaire LET being the predominant technique. This aligns with recent clinical studies showing improved outcomes and reduced risk of failure in ACLR with lateral augmentation compared to ACLR alone., Level of Evidence: Level V, Expert Opinion., Competing Interests: Declaration of Competing Interest P.A.S. reports board or committee membership in the Arthroscopy Association of North America, as well as editorial or governing board membership of Journal of Knee Surgery. He is a consultant for Arthrex, and also receives speaker’s fees, royalties and research support from Arthrex. He is s stockholder in Spinal Simplicity. V.M. reports a relationship with Smith and Nephew Inc including consulting or advisory, funding grants, and speaking and lecture fees, funding grants from Arthrex, a relationship with International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine that includes board membership, consulting for Newclip consulting, and a shareholder of Ostesys. P.C.M.V. receives royalties from ConMed. B.S.-C. has received consulting fees and royalties from Arthrex and stock options held in AREAS. A.G. receives grant support from Canadian Institutes of Health Research, National Institutes of Health, Canadian Foundation for Innovation, Ontario Research Fund, Smith & Nephew, and Ossur, outside the submitted work; receives personal fees from Smith & Nephew; is on the advisory board of Spring Loaded Technologies; and owns stock in Precision OS, LinkX Robotics, and Ostesys Robotics. S.L.S. reports consultant fees from Arthrex, other from BioVentus, other from CONMEDLinvatec, JRFOrtho, other from Kinamed, Smith & Nephew, and Vericel; speaking fees from Arthrex, CONMEDLinvatec, Joint Restoration Foundation, Kinamed, Smith & Nephew, and Vericel; stock/stock options held in Epic Bio, Reparel, Sarcio, and Vivorte; and royalties from CONMEDLinvateco., (Copyright © 2024. Published by Elsevier Inc.)

Congenital heart defects (CHDs) are the most common structural birth defect and are present in 40-50% of children born with Down syndrome (DS). To characterize the genetic architecture of DS-associated CHD, we sequenced genomes of a multiethnic group of children with DS and a CHD (n=886: atrioventricular septal defects (AVSD), n=438; atrial septal defects (ASD), n=122; ventricular septal defects (VSD), n=170; other types of CHD, n=156) and DS with a structurally normal heart (DS+NH, n=572). We performed four GWAS for common variants (MAF>0.05) comparing DS with CHD, stratified by CHD-subtype, to DS+NH controls. Although no SNP achieved genome-wide significance, multiple loci in each analysis achieved suggestive significance (p<2×10 -6 ). Of these, the 1p35.1 locus (near RBBP4 ) was specifically associated with ASD risk and the 5q35.2 locus (near MSX2 ) was associated with any type of CHD. Each of the suggestive loci contained one or more plausible candidate genes expressed in the developing heart. While no SNP replicated (p<2×10 -6 ) in an independent cohort of DS+CHD (DS+CHD: n=229; DS+NH: n=197), most SNPs that were suggestive in our GWASs remained suggestive when meta-analyzed with the GWASs from the replication cohort. These results build on previous work to identify genetic modifiers of DS-associated CHD.

Female gender is one of the commonly mentioned risk factors for anterior knee pain (AKP), among a spectrum of other factors including anatomical, biomechanical, hormonal, behavioral and psychological elements contributing to its development. Despite the focus on individual risk factors, there's a notable gap in comprehending how gender influences and interacts with other risk factors. The objective of this review was to identify and emphasize the connections between these interactions, gender-related risk factors for AKP, and the potential mechanisms that explain their associations with other risk factors, aiming to aid in the creation of precise prevention and treatment approaches. Gender influences the majority of risk factors for AKP, including anatomical, biomechanical, hormonal, behavioral and psychological factors. Women have on average smaller patellae, higher patellofemoral cartilage stress and for AKP, disadvantageous trochlear morphology, ligament and muscle composition and unfavorable neuromuscular control pattern. In contrast, men show on average an increased ability to strengthen their hip external rotators, which are both protective against AKP. Particularly in kinetic and kinematic analysis, men have been shown to have a distinctly different risk factor profile than women. Sex hormones may also play a role in the risk of AKP, with estrogen potentially influencing ligamentous laxity, increasing midfoot loading and affecting neuromuscular control of the lower extremities and testosterone positively affecting muscle mass and strength. The higher incidence of AKP in women is likely due to a combination of slightly increased risk factors. Although all risk factors can be present in both men and women and the holistic evaluation of each individual's risk factor composition is imperative regardless of gender, knowing distinctive risk factors may help with focused evaluation, treatment and implementing preventive measures of AKP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anna Bartsch reports financial support was provided by Zaeslin Foundation, Martin Allgöwer Foundation and AO Trauma Switzerland. Dr. Sherman holds committee positions for AANA, AAOS, ACLSG, AOSSM, Biologic Association, ICRS and ISAKOS. He is on the editorial board for the Arthroscopy Journal, Cur Rev Musc Med, and VJSM. He is a course chair of ISMF and the PFF Masters Course and a member of the AO Sports Medicine Taskforce., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Image-guided ultrasound or fluoroscopic glenohumeral injections have high accuracy rates but require training, equipment, cost, and radiation exposure (fluoroscopy). In contrast, landmark-guided glenohumeral injections do not require additional subspecialist referrals or equipment. An optimal technique would be safe and accurate and have few barriers to implementation. The purpose of this study was to define the accuracy of glenohumeral needle placement via an anterior landmark-guided approach as assessed by direct arthroscopic visualization., Methods: A consecutive series of adult patients undergoing shoulder arthroscopy in the beach chair position were included in this study. Demographic and procedural data were collected. The time required to perform the injection, the precise location of the needle tip, and factors that affected the accuracy of the injection were also assessed., Results: A standardized anterior landmark-guided glenohumeral joint injection was performed in the operating room prior to surgery, and the location of the needle tip was documented by arthroscopic visualization with a low complication profile and few barriers to implementation. A total of 81 patients were enrolled. Successful intra-articular glenohumeral needle placement by sports medicine and shoulder/elbow fellowship-trained orthopedic surgeons was confirmed in 93.8% (76/81) of patients. The average time to complete the procedure was 24.8 ​s. There were no patient-related variables associated with nonintra-articular injections in the cohort., Conclusions: This study demonstrated that the technique of anterior landmark-guided glenohumeral injection has an accuracy of 93.8% and requires less than 30 ​s to perform. This method is safe, yields similar accuracy to image-guided procedures, has improved cost and time efficiency, and requires less radiation exposure. No patient-related factors were associated with inaccurate needle placement. Anterior landmark-guided glenohumeral injections may be utilized with confidence by providers in the clinical setting., Level of Evidence: Level 5. IRB: Approved under Stanford IRB-56323., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Geoffry Abrams, MD reports a relationship with Orthofix Medical Inc that includes: funding grants. Geoffrey Abrams, MD reports a relationship with Smith and Nephew Inc that includes: funding grants. Geoffrey Abrams, MD reports a relationship with Sparta Bio that includes: equity or stocks. Geoffrey Abrams, MD reports a relationship with AxGen that includes: equity or stocks. Geoffrey Abrams, MD reports a relationship with Cytonics Inc that includes: equity or stocks and non-financial support. Geoffrey Abrams, MD reports a relationship with Arthrex Inc that includes: non-financial support. Geoffrey Abrams, MD reports a relationship with Stryker Orthopedics that includes: non-financial support. Geoffrey Abrams, MD reports a relationship with RobiconMD that includes: non-financial support. Geoffrey Abrams, MD reports a relationship with Bioventus that includes: non-financial support. Michael T. Freehill, MD reports a relationship with Conmed that includes: funding grants. Michael T. Freehill, MD reports a relationship with Smith and Nephew Inc that includes: consulting or advisory. MIchael T. Freehill, MD reports a relationship with Stryker Orthopedics that includes: consulting or advisory. Michael T. Freehill, MD reports a relationship with Sparta Bio that includes: equity or stocks. Tim Wang, MD reports a relationship with Overture Orthopedics that includes: equity or stocks. Tim Wang, MD reports a relationship with Micah that includes: non-financial support., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

High tibial osteotomy is a dynamic operation, used as an effective procedure in both joint preservation and knee stability. Applications and indications are expanding, with good results in the treatment of malalignment associated with arthrosis, knee instability, meniscus deficiency or transplants, and/or cartilage restoration. Appropriate patient selection and preoperative planning are critical to achieving good outcomes after surgery. Coronal and sagittal plane corrections made through the proximal tibia can effectively alter joint mechanics creating a more favorable environment for cartilage, meniscus, and ligamentous structures about the knee. Advancing techniques and technologies have allowed for more precise planning and execution of osteotomies., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Anterior cruciate ligament (ACL) injuries continue to be a prevalent concern among athletes and individuals with an active lifestyle. Traditionally, the standard of care for ACL tears has involved surgical reconstruction using autograft or allograft. This article aims to provide an overview of the evolving landscape of primary ACL repair, examining the current evidence, surgical techniques, patient selection criteria, outcomes, and potential future directions in this field., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure: The authors declare no conflict of interest.

Background: Elbow ulnar collateral ligament (UCL) repair with suture brace augmentation shows good time-zero biomechanical strength and a more rapid return to play compared with UCL reconstruction. However, there are concerns about overconstraint or stress shielding with nonabsorbable suture tape. Recently, a collagen-based bioinductive absorbable structural scaffold has been approved by the Food and Drug Administration for augmentation of soft tissue repair., Purpose/hypothesis: This study aimed to assess the initial biomechanical performance of UCL repair augmented with this scaffold. We hypothesized that adding the bioinductive absorbable structural scaffold to primary UCL repair would impart additional time-zero restraint to the valgus opening., Study Design: Controlled laboratory study., Methods: Eight cadaveric elbow specimens-from midforearm to midhumerus-were utilized. In the native state, elbows underwent valgus stress testing at 30 o , 60 o , and 90 o of flexion, with a cyclical valgus rotational torque. Changes in valgus rotation from 2- to 5-N·m torque were recorded as valgus gapping. Testing was then performed in 4 states: (1) native intact UCL-with dissection through skin, fascia, and muscle down to an intact UCL complex; (2) UCL-transected-distal transection of the ligament off the sublime tubercle; (3) augmented repair with bioinductive absorbable scaffold; and (4) repair alone without scaffold. The order of testing of repair states was alternated to account for possible plastic deformation during testing., Results: The UCL-transected state showed the greatest increase in valgus gapping of all states at all flexion angles. Repair alone showed similar valgus gapping to that of the UCL-transected state at 30° ( P = .62) and 60° of flexion ( P = .11). Bioinductive absorbable scaffold-augmented repair showed less valgus gapping compared with repair alone at all flexion angles ( P = .021, P = .024, and P = .024 at 30°, 60°, and 90°, respectively). Scaffold-augmented repair showed greater gapping compared with the native state at 30° ( P = .021) and 90° ( P = .039) but not at 60° of flexion ( P = .059). There was no difference when testing augmented repair or repair alone first., Conclusion: UCL repair augmented with a bioinductive, biocomposite absorbable structural scaffold imparts additional biomechanical strength to UCL repair alone, without overconstraint beyond the native state. Further comparative studies are warranted., Clinical Relevance: As augmented primary UCL repair becomes more commonly performed, use of an absorbable bioinductive scaffold may allow for improved time-zero mechanical strength, and thus more rapid rehabilitation, while avoiding long-term overconstraint or stress shielding., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: K.M.L. has received support for education from Smith & Nephew and Arthrex. R.A. has received support for education from Smith & Nephew, Evolution Surgical, and Arthrex. S.L.S. has received royalties from ConMed, DJO, and Osteosys; consulting fees from Active Implants, Allosource, AO, Arcuro, Arthrex, Biorez, Bioventus, ConMed, Depuy J&J, DJO, Flexion, Icarus Bracing, JRF, Kinamed, LifeNet, Medical Device Business Services, NewClip, Olympus America, Ostesys, Pacira Pharmaceuticals, Reparel, Sarcio, Smith & Nephew, Sparta Biomedical, Vericel, and Vivorte; royalties from Linvatec Corporation; and support for education from Evolution Surgical and Elite Orthopaedics; and holds stock or stock options in Sarcio, Vivorte, Ostesys, and Reparel. M.R.S. has received consulting fees from Anika Therapeutics, Medacta, and Smith & Nephew; royalties from DJ Orthopedics, Smith & Nephew, and Stryker; and research support and fellowship support from Smith & Nephew; holds stock/stock options in Biomedica and Subchondral Solutions; and received publishing royalties from Saunders/Mosby-Elsevier and Wolters Kluwer Health–Lippincott Williams & Wilkins. M.T.F. has received consultant fees from Conmed Corp, Smith & Nephew, Tornier/Stryker Corp, Biorez, and Sparta Biopharma; royalties from Smith & Nephew; research support from Major League Baseball, Smith & Nephew, RTI, Arthrex, Xiros, Biorez, and Conmed; and hospitality payments from Xiros and Integra LifeSciences Corp. 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.

Objective: To compare MRI features of medial and lateral patellar stabilizers in patients with and without patellar instability., Methods: Retrospective study of 196 patients (mean age, 33.1 ± 18.5 years; 119 women) after diagnosis of patellar instability (cohort-1, acute patellar dislocation; cohort-2, chronic patellar maltracking) or no patellar instability (cohort-3, acute ACL rupture; cohort-4, chronic medial meniscus tear). On MRI, four medial and four lateral stabilizers were evaluated for visibility and injury by three readers independently. Inter- and intra-reader agreement was determined., Results: Medial and lateral patellofemoral ligaments (MPFL and LPFL) were mostly or fully visualized in all cases (100%). Of the secondary patellar stabilizers, the medial patellotibial ligament was mostly or fully visualized in 166 cases (84.7%). Other secondary stabilizers were mostly or fully visualized in only a minority of cases (range, 0.5-32.1%). Injury scores for all four medial stabilizers were higher in patients with acute patellar dislocation than the other 3 cohorts (p < .05). Visibility inter- and intra-reader agreement was good for medial stabilizers (κ 0.61-0.78) and moderate-to-good for lateral stabilizers (κ 0.40-0.72). Injury inter- and intra-reader agreement was moderate-to-excellent for medial stabilizers (κ 0.43-0.90) and poor-to-moderate for lateral stabilizers (κ 0-0.50)., Conclusion: The MPFL and LPFL were well visualized on MRI while the secondary stabilizers were less frequently visualized. The secondary stabilizers were more frequently visualized medially than laterally, and patellotibial ligaments were more frequently visualized compared to the other secondary stabilizers. Injury to the medial stabilizers was more common with acute patellar dislocation than with chronic patellar maltracking or other knee injuries., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Purpose: To determine the cost-effectiveness of meniscal repair (MR) using an all-suture-based technique when compared to partial meniscectomy (PM) for horizontal cleavage tears (HCTs) from a payor's perspective in the United States., Methods: A state-transition model and cost-utility analysis were developed from a US payor's perspective to project treatment costs and quality-adjusted life-years (QALYs) in a cohort of 35-year-old patients without osteoarthritis at baseline and presenting with either a lateral or medial HCT. Two outpatient costing perspectives were used, namely ambulatory surgical centers (ASCs) and hospitals. The state-transition model had 7 health states with transition probabilities, costs, and utilities obtained from the existing literature. Cost-effectiveness was assessed using a willingness-to-pay threshold of $100,000/QALY, and sensitivity analysis considered the effects of parameter uncertainty on model results. MR failure rates were focused on an all-suture-based technique; however, in a separate scenario, this study considered effectiveness data from various MR techniques and devices., Results: MR dominated PM over a lifetime horizon, increasing QALYs by 0.43 per patient and decreasing the cost by $12,227 per patient within a hospital setting (and by $12,570 within an ASC). MR with an all-suture-based technique continued to be the dominant treatment when age at primary treatment was varied between 30 and 60 years. Sensitivity analysis showed that MR was not cost-effective in year 1, was cost-effective from year 2, and was cost-saving from year 6 onward from both ASC and hospital perspectives. Probabilistic sensitivity analysis found that MR was cost-effective over a lifetime horizon in 99% of 10,000 iterations on base-case analysis., Conclusions: Using a lifetime horizon, this study found that from a payor's perspective, MR is a cost-saving intervention when compared with PM in patients with an HCT., Level of Evidence: Level III, economic analysis., Competing Interests: The authors report the following potential conflicts of interest or sources of funding: N.A. is employed by Smith & Nephew. L.M.N. is employed by Smith & Nephew. R.J.S. is employed by Smith and Nephew and reports other funding from Smith & Nephew, during the conduct of the study and funding outside the submitted work. D.C.F. is a consultant for Smith & Nephew, DePuy Mitek, Vericel, and ConMed; receives research support from 10.13039/100009026Smith & Nephew, 10.13039/100008426DePuy Mitek, Vericel, ConMed, Moximed, Episurf, KCRN, 10.13039/100014927Anika Therapeutics, and Aesculap, outside the submitted work. All other authors declare that they have no known competing financial interests or personal relation, (© 2023 The Authors.)

Purpose: To establish consensus statements on platelet-rich plasma (PRP) for the treatment of musculoskeletal pathologies., Methods: A consensus process on the treatment of PRP using a modified Delphi technique was conducted. Thirty-five orthopaedic surgeons and sports medicine physicians participated in these consensus statements on PRP. The participants were composed of representatives of the Biologic Association, representing 9 international orthopaedic and musculoskeletal professional societies invited due to their active interest in the study of orthobiologics. Consensus was defined as achieving 80% to 89% agreement, strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement., Results: There was consensus on 62% of statements about PRP., Conclusions: (1) PRP should be classified based on platelet count, leukocyte count, red blood count, activation method, and pure-plasma versus fibrin matrix; (2) PRP characteristics for reporting in research studies are platelet count, leukocyte count, neutrophil count, red blood cell count, total volume, the volume of injection, delivery method, and the number of injections; (3) the prognostic factors for those undergoing PRP injections are age, body mass index, severity/grade of pathology, chronicity of pathology, prior injections and response, primary diagnosis (primary vs postsurgery vs post-trauma vs psoriatic), comorbidities, and smoking; (4) regarding age and body mass index, there is no minimum or maximum, but clinical judgment should be used at extremes of either; (5) the ideal dose of PRP is undetermined; and (6) the minimal volume required is unclear and may depend on the pathology., Level of Evidence: Level V, expert opinion., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: Mesenchymal stem cells/medicinal signaling cells (MSCs) possess therapeutic potential and are used in regenerative orthopaedics. The infra-patellar fat pad (IFP) is partially resected during knee arthroscopy (KASC) and contains MSCs. Heat, irrigation, and mechanical stress during KASC may decrease MSC's therapeutic potential. This study assessed MSCs' regenerative potential after arthroscopic IFP harvest and potential effects of two blood products (BP) (platelet-rich plasma (PRP), hyperacute serum (HAS)) on MSCs' viability and chondrogenic differentiation capacity., Methods: IFP was arthroscopically harvested, isolated, and counted (n = 5). Flow cytometry was used to assess cell viability via staining with annexin V/7-AAD and stemness markers via staining for CD90, CD73, and CD105. MSCs were incubated with blood products, and metabolic activity was determined via an XTT assay. Deposition of cartilage extracellular matrix was determined in histologic sections of chondrogenically differentiated 3D pellet cultures via staining with Alcian Blue. Expression of cartilage-specific genes (SOX9, MMP3/13, ACAN, COL1/2) was analyzed via quantitative PCR., Results: MSC isolation from IFP yielded 2.66*10 6  ± 1.49*10 6 viable cells from 2.7 (0.748) g of tissue. MSC markers (CD 90/105/73) were successfully detected and annexin V staining showed 81.5% viable cells. XTT showed increased metabolic activity. Within the BP groups, this increase was significant (days 0-14, p < 0.05). PCR showed expression of cartilage-specific genes in each group. COL2 (p < 0.01) as well as ACAN (p < 0.001) expression levels were significantly higher in the HAS group. Histology showed successful differentiation., Conclusion: Arthroscopic harvest of IFP-MSCs yields sufficient cells with maintained regenerative potential and viability. Blood products further enhance MSCs' viability., (© 2023. The Author(s).)

Aims: The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process., Methods: This was the second part of a study dealing with these aspects of management in these patients. As in part I, a total of 60 surgeons from 11 countries contributed to the development of consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered unanimous., Results: Of 41 questions and statements on patellar instability, none achieved unanimous consensus, 19 achieved strong consensus, 15 achieved consensus, and seven did not achieve consensus., Conclusion: Most statements reached some degree of consensus, without any achieving unanimous consensus. There was no consensus on the use of anchors in MPFL reconstruction, and the order of fixation of the graft (patella first versus femur first). There was also no consensus on the indications for trochleoplasty or its effect on the viability of the cartilage after elevation of the osteochondral flap. There was also no consensus on postoperative immobilization or weightbearing, or whether paediatric patients should avoid an early return to sport., Competing Interests: S. L. Sherman reports royalties or licenses from CONMED Linvatec, consulting fees from Arthrex, BioVentus, JRF Ortho, Kinamed, Smith & Nephew, Vericel, CONMED Linvatec, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Arthex, Joint Restoration Foundation, Kinamed, Smith & Nephew, and Vericel, and stock or stock options from Epic Bio, Reparel, Sarcio, and Vivorte, all of which are unrelated to this study. J. Chahla reports consulting fees from Arthrex, CONMED Linvatec, Ossur, and Smith & Nephew, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Smith & Nephew, all of which are unrelated to this study. M. J. Alaia reports consulting fees from BodyCad, JRF Ortho, and Mitek, institutional grants from Orcosa, and royalties from Springer, all of which are unrelated to this study. M. J. Tanaka reports grants or contracts from FujiFilm, royalties or licenses from Verywell, and consulting fees from Depuy Synthes, all of which are unrelated to this study. J. L. Pace reports consulting fees from Arthrex and JRF Ortho, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Arthrex, and stock or stock options from OutcomeMD, all of which are unrelated to this study. L. M. Jazwari reports grants or contracts from Arthrex, Mitek, Smith & Nephew, and Wolters Kluwer Health, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Wolters Kluwer Health, and stock or stock options from Lazurite, all of which are unrelated to this study., (© 2023 The British Editorial Society of Bone & Joint Surgery.)

➤ Joint alignment, meniscal status, and ligament stability are codependent factors involved in knee joint preservation, and any injury or imbalance can impact the knee articular cartilage status and can result in adverse clinical outcomes.➤ Cartilage preservation procedures in the knee will not result in optimal outcomes if there is joint malalignment, meniscal deficiency, or ligamentous instability.➤ Lower-extremity varus or valgus malalignment is a risk factor for the failure of an anterior cruciate ligament (ACL) reconstruction. It represents an indication for a high tibial osteotomy or distal femoral osteotomy in the setting of failed ACL reconstruction, and may even be considered in patients who have an initial ACL injury and severe malalignment.➤ An elevated posterior tibial slope increases the risk of failure of ACL reconstruction, whereas a decreased posterior tibial slope increases the risk of failure of posterior cruciate ligament reconstruction., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H657 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Developmental dysplasia of the hip (DDH) and trochlear dysplasia (TD) are distinct pathologies with several important features in common. In addition to shared risk factors, both forms of dysplasia cause abnormal joint kinematics and force transmission, predisposing patients to pain, injuries to cartilage and soft tissue stabilizers, and ultimately arthritis., Purpose: To evaluate for an association between hip dysplasia and TD in skeletally mature patients with symptomatic hip dysplasia., Study Design: Cross-sectional study; Level of evidence, 3., Methods: A total of 48 patients with DDH who underwent periacetabular osteotomy were compared with 48 sex-matched patients who underwent hip arthroscopy for femoroacetabular impingement (FAI) between July 2014 and February 2021. All patients were skeletally mature. The Tönnis angle and lateral center-edge angle were measured on preoperative pelvis radiographs. Femoral version, trochlear depth, lateral trochlear inclination (LTI), tibial tubercle-trochlear groove distance (TTTG-d), and posterior lateral condylar angle (PLCA) were measured on preoperative magnetic resonance imaging scans of the symptomatic hip and ipsilateral knee. Continuous variables were compared between the patient groups using 2-sample t tests. Interobserver reliability was measured using the intraclass correlation coefficient., Results: Patients with DDH demonstrated a reduced trochlear depth compared with patients with FAI (3.6 vs 4.6 mm; P < .001). There were no differences between groups in femoral anteversion, LTI, TTTG-d, or PLCA. Two (4.2%) patients with FAI and 17 (35.4%) patients with DDH had a trochlear depth <3 mm ( P < .001). One (2.1%) patient with FAI and 7 (14.6%) patients with DDH had an LTI <11° ( P = .027). There was no difference between groups in frequency of a convex proximal trochlea, patient-reported ipsilateral knee pain, or ipsilateral knee procedures., Conclusion: Patients with DDH had reduced trochlear depth compared with patients with FAI, demonstrating a higher incidence of dysplastic trochlear features that may predispose patients to patellofemoral joint disease. Further research is needed to determine whether screening at-risk patients and treating TD will help to prevent symptomatic patellofemoral disease., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.T.F. has received education payments from Evolution Surgical. S.L.S. has received education payments from Evolution Surgical and Elite Orthopedics; consulting fees from Bioventus, DJO, Kinamed, Linvatec, Olympus America, Ceterix Orthopaedics, Pacira Therapeutics, Smith & Nephew, Vericel, JRF Ortho, LifeNet Health, and Flexion Therapeutics; nonconsulting fees from Arthrex, Linvatec, Smith & Nephew, and Synthes GmbH; royalties from Linvatec and ConMed; hospitality payments from Aesculap Biologics; and honoraria from Flexion Therapeutics, JRF Ortho, and Vericel. K.G.S. has received education payments from Evolution Surgical and hospitality payments from Arthrex. 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. Ethical approval for this study was obtained from Stanford University (No. 5136)., (© The Author(s) 2023.)

The infrared predissociation spectra of the Gly 3 H + (H 2 O) 1-2 and Ala 3 H + (H 2 O) 1-2 clusters are presented and analyzed with the goal of revealing the influence of methyl side chains on the microsolvated structures of these flexible tripeptides. We have shown previously that the presence of methyl side chains can modulate the strengths of the intramolecular hydrogen bonds, thereby influencing the structures adopted by the bare tripeptides composed of glycine and alanine residues. This effect was attributed to the electron-donating nature of the methyl group, whose presence alters the proton affinities of the functional groups that are involved in hydrogen bonding. Here, we expand this work to the microsolvated tripeptides to determine how the effects of the presence of the methyl group evolve with the addition of water solvent molecules. For each solvated cluster, we found multiple solvated structures present, and their relative populations were disentangled using isomer-specific spectroscopic techniques and comparisons to calculation. The results showed that while the glycine and alanine tripeptides display similar structures for the dominant solvation population, they do have different structures for their minor solvation constituents stemming from their different bare tripeptide structures. The relative populations of these minor constituents indicate that the influence of the methyl side chain on intramolecular hydrogen bonding persists to some extent with solvation.

Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Seth L. Sherman, MD, reports relationships with American Orthopedic Society for Sports Medicine; Arthrex; Arthoscopy; BioVentus; Biologics Alliance; CONMED Linvatec; Current Reviews in Musculoskeletal Medicine; DJO; Epic Bio; International Cartilage Regeneration & Joint Preservation Society; Icarus Bracing; International Society of Arthroscopy, Knee Surgery, and Orthopedic Sports Medicine; International Sports Medicine Fellows Conference; JRF Ortho; Kinamed; LifeNet, NewClip, Ostesys; Patellofemoral Foundation; Reparel; Sarcio; Smith & Nephew; Sparta Biomedical; Vericel; and Vivorte. The other authors declare no potential conflicts of interest.

Introduction: Lateral meniscus transplantation successfully treats symptomatic meniscus deficiency in children. Although clinical outcomes are well-characterized, joint forces in meniscus-deficient and transplant states are unknown. The purpose of this study was to characterize contact area (CA) and contact pressures (CP) of transplanted lateral meniscus in pediatric cadavers. We hypothesize that (1) compared with the intact state, meniscectomy will decrease femorotibial CA and increase CP, and increase contact pressure (CP) and (2) compared with the meniscectomy state, meniscus transplantation will improve contact biomechanics toward the intact meniscus state., Methods: Pressure-mapping sensors were inserted underneath the lateral meniscus of eight cadaver knees aged 8 to 12 years. CA and CP on the lateral tibial plateau were measured in the intact, meniscectomy, and transplant states each at 0°, 30°, and 60° of knee flexion. Meniscus transplant was anchored with transosseous pull-out sutures and sutured to the joint capsule with vertical mattresses. The effects of meniscus states and flexion angle on CA and CP were measured by a two-way analysis of variance repeated measures model. One-way analysis of variance measured pairwise comparisons between meniscus states., Results: Regarding CA, at 0°, no differences between the groups reached significance. Meniscectomy reduced CA at 30° ( P = 0.043) and 60° ( P = 0.001). Transplant and intact states were comparable at 30°. At 60°, transplant significantly increased CA ( P = 0.04). Regarding contact pressure, the average pressure increased with meniscectomy at all angles of flexion (0° P = 0.025; 30° P = 0.021; 60° P = 0.016) and decreased with transplant relative to respective intact values. Peak pressure increased with meniscectomy at 30° ( P = 0.009) and 60° ( P = 0.041), but only reached intact comparable values at 60°. Pairwise comparisons support restoration of average CP with transplant, but not peak CP., Discussion: Pediatric meniscus transplantation improves average CP and CA more than peak CP, but does not completely restore baseline biomechanics. Net improvements in contact biomechanics after transplant, relative to the meniscectomy state, support meniscus transplant., Study Design: Descriptive laboratory study, Level III., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Background: Tibial spine fractures are common in the pediatric population because of the biomechanical properties of children's subchondral epiphyseal bone. Most studies in porcine or adult human bone suggest that suture fixation performs better than screw fixation, but these tissues may be poor surrogates for pediatric bone. No previous study has evaluated fixation methods in human pediatric knees., Purpose: To quantify the biomechanical properties of 2-screw and 2-suture repair of tibial spine fracture in human pediatric knees., Study Design: Controlled laboratory study., Methods: Cadaveric specimens were randomly assigned to either 2-screw or 2-suture fixation. A standardized Meyers-Mckeever type 3 tibial spine fracture was induced. Screw-fixation fractures were reduced with two 4.0-mm cannulated screws and washers. Suture-fixation fractures were reduced by passing 2 No. 2 FiberWire sutures through the fracture fragment and the base of the anterior cruciate ligament. Sutures were secured through bony tunnels over a 1-cm tibial cortical bridge. Each specimen was mounted at 30° of flexion. A cyclic loading protocol was applied to each specimen, followed by a load-to-failure test. Outcome measures were ultimate failure load, stiffness, and fixation elongation., Results: Twelve matched pediatric cadaveric knees were tested. Repair groups had identical mean (8.3 years) and median (8.5 years) ages and an identical number of samples of each laterality. Ultimate failure load did not significantly differ between screw (mean ± SD, 143.52 ± 41.9 7 N) and suture (135.35 ± 47.94 N) fixations ( P = .760). Screws demonstrated increased stiffness and decreased elongation, although neither result was statistically significant at the .05 level (21.79 vs 13.83 N/mm and 5.02 vs 8.46 mm; P = .076 and P = .069, respectively)., Conclusion: Screw fixation and suture fixation of tibial spine fractures in human pediatric tissue were biomechanically comparable., Clinical Relevance: Suture fixations are not biomechanically superior to screw fixations in pediatric bone. Pediatric bone fails at lower loads, and in different modes, compared with adult cadaveric bone and porcine bone. Further investigation into optimal repair is warranted, including techniques that may reduce suture pullout and "cheese-wiring" through softer pediatric bone. This study provides new biomechanical data regarding the properties of different fixation types in pediatric tibial spine fractures to inform clinical management of these injuries.

Background: Although objective outcomes assessing knee function are essential measurements for return to sport, psychological factors have become increasingly recognized as equally important parameters for determining an athlete's ability to return to sport after surgery., Purpose: To systematically review the literature to determine whether patients who returned to sport after anterior cruciate ligament (ACL) reconstruction had improved psychological scores (as measured with validated questionnaires) compared with patients who did not return to sport., Study Design: Systematic review and meta-analysis; Level of evidence, 3., Methods: A systematic review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and was preregistered on PROSPERO. Four databases were searched for level 1 to 3 studies that compared at least 1 psychological outcome measured by a validated questionnaire for patients who did and did not return to sport after primary ACL reconstruction. The following data were recorded: study and patient characteristics; psychological metrics (ACL-Return to Sport Injury [ACL-RSI] scale, Knee Self-Efficacy Scale [K-SES], and Tampa Scale of Kinesiophobia [TSK/TSK-11]); International Knee Documentation Committee (IKDC) score; and clinical metrics. Study methodological quality was analyzed using the methodological index for non-randomized studies (MINORS), and the mean difference (MD) and 95% CI were calculated for each psychological outcome score using the inverse variance method., Results: We included and analyzed 16 articles (3744 patients; 38.9% female; mean age range, 17-28.7 years; mean MINORS score, 19.9 ± 1.4). Overall, 61.8% of athletes returned to sport (66.8% of male patients; 55.4% of female patients). Patients who returned scored significantly higher on the ACL-RSI scale (MD, 20.8; 95% CI, 15.9 to 25.7; P < .001), significantly higher on the K-SES (MD, 1.3; 95% CI, 0.2 to 2.3; P = .036), and significantly lower on the TSK/TSK-11 (MD, 10.1%; 95% CI, -12.1% to -8.2%; P = .004). Those returning to sport did not exceed the minimal clinically important difference for IKDC score versus those not returning to sport., Conclusion: Patients who returned to sport after primary ACL reconstruction had significantly higher psychological readiness, higher self-efficacy, and lower kinesiophobia compared with those who did not return to sport, despite having clinically similar knee function scores. Evaluation of psychological readiness, in combination with other objective measurements, is a critical component of return-to-sport evaluation in athletes after primary ACL reconstruction., Registration: CRD42021284735 (PROSPERO).

Numerous in vitro studies suggest higher osmolarity irrigation fluids potentiate a chondroprotective environment, and a recent clinical study using hyperosmolar saline for shoulder arthroscopy reported potential clinical advantages. This prospective randomized double-blind controlled clinical trial was designed to assess initial clinical outcomes associated with use of a hyperosmolar irrigation solution in patients undergoing arthroscopic knee surgery. With institutional review board approval and informed consent, patients scheduled for arthroscopic knee surgery were randomized to surgery with either isotonic lactated Ringer's (273 mOsm/L) or hyperosmolar saline (593 mOsm/L) irrigation solution. Outcomes included perioperative blood pressure, knee girth, visual analogue scale (VAS) pain scores, and narcotic pain medication consumption. Forty-six patients underwent arthroscopic knee surgery with isotonic ( n  = 23) or hyperosmolar ( n  = 23) irrigation fluids. There were 11 males and 12 females (mean age = 44.0 years) in the isotonic cohort and 8 males and 15 females (mean age = 40.2 years) in the hyperosmolar cohort. There were no significant differences with respect to surgical duration (pump time) or amount of irrigation fluid used between the two cohorts. There were no significant differences with respect to change in knee girth, blood pressure, or VAS pain scores. However, patients treated with hyperosmolar saline consumed less narcotic medication on postoperative day 3 (4.0 ± 7.6 vs. 15.5 ± 17.4 mg, p  = 0.01). The results of this randomized clinical trial suggest that a hyperosmolar irrigation solution is safe and relatively inexpensive for use in patients undergoing arthroscopic knee surgery and contributes to a reduction in initial postoperative narcotic pain medication consumption. A hyperosmolar saline irrigation fluid was not associated with any detrimental effects on the execution of the surgical procedure, postoperative pain, or periarticular fluid extravasation. Taken together with previous basic science, translational, and clinical studies, hyperosmolar saline irrigation fluid is promising alternative to traditional isotonic irrigation fluids for knee arthroscopy. This study is a prospective trial and reflects level of evidence I., Competing Interests: J.L.C. reports grants and personal fees from Arthrex, Inc., personal fees from Bioventus, grants from Coulter Foundation, grants from DePuy Synthes, grants from GE Healthcare, other from Journal of Knee Surgery, grants from Merial, other from Midwest Transplant Network, grants, personal fees and other from Musculoskeletal Transplant Network, grants from National Institutes of Health (NIAMS & NICHD), grants from Purina, personal fees and other from Thieme, personal fees from Trupanion, grants from U.S. Department of Defense, outside the submitted work. J.P.S. reports other from American Orthopaedic Association, other from AO Foundation, other from AO North America, grants and personal fees from Arthrex, Inc., grants from Coulter Foundation, personal fees from DePuy Synthes, other from Journal of Knee Surgery, other from Mid-America Orthopaedic Association, grants from National Institutes of Health (NIAMS & NICHD), personal fees from Orthopedic Designs North America, personal fees from Smith & Nephew, other from Thieme, grants from U.S. Department of Defense, outside the submitted work. M.J.S. reports grants and personal fees from Arthrex, Inc., grants and personal fees from DePuy Synthes, personal fees from Ignite Orthopedics, grants from Wright Medical Technology, Inc., outside the submitted work. R.M. reports other from American Orthopaedic Association, other from American Orthopaedic Society for Sports Medicine, grants from Cartiheal, other from Journal of Bone and Joint Surgery AM, grants from Moximed, other from Orthopaedic Research Society, other from Rugby Research Injury Prevention Group, outside the submitted work. S.L.S. reports other from ACL Study Group, other from American Orthopaedic Society for Sports Medicine, grants and personal fees from Arthrex, Inc., other from Arthroscopy, other from Arthroscopy Association of North America, personal fees from Ceterix Orthopaedics, personal fees from CONMED Linvatex, personal fees from Flexion Therapeutics, personal fees from GLG Consulting, other from International Cartilage Restoration & Joint Preservation Society, other from International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine, personal fees from JRF Ortho, personal fees from Linvatec, personal fees from Moximed, personal fees from Olympus, personal fees from RTI Surgical, personal fees from Smith & Nephew, personal fees from Vericel, outside the submitted work., (Thieme. All rights reserved.)

Trisomy 21, the genetic cause of Down syndrome (DS), is the most common congenital chromosomal anomaly. It is associated with a 20-fold increased risk of acute lymphoblastic leukemia (ALL) during childhood and results in distinctive leukemia biology. To comprehensively define the genomic landscape of DS-ALL, we performed whole-genome sequencing and whole-transcriptome sequencing (RNA-Seq) on 295 cases. Our integrated genomic analyses identified 15 molecular subtypes of DS-ALL, with marked enrichment of CRLF2-r, IGH::IGF2BP1, and C/EBP altered (C/EBPalt) subtypes compared with 2257 non-DS-ALL cases. We observed abnormal activation of the CEBPD, CEBPA, and CEBPE genes in 10.5% of DS-ALL cases via a variety of genomic mechanisms, including chromosomal rearrangements and noncoding mutations leading to enhancer hijacking. A total of 42.3% of C/EBP-activated DS-ALL also have concomitant FLT3 point mutations or insertions/deletions, compared with 4.1% in other subtypes. CEBPD overexpression enhanced the differentiation of mouse hematopoietic progenitor cells into pro-B cells in vitro, particularly in a DS genetic background. Notably, recombination-activating gene-mediated somatic genomic abnormalities were common in DS-ALL, accounting for a median of 27.5% of structural alterations, compared with 7.7% in non-DS-ALL. Unsupervised hierarchical clustering analyses of CRLF2-rearranged DS-ALL identified substantial heterogeneity within this group, with the BCR::ABL1-like subset linked to an inferior event-free survival, even after adjusting for known clinical risk factors. These results provide important insights into the biology of DS-ALL and point to opportunities for targeted therapy and treatment individualization., (© 2023 by The American Society of Hematology.)

Menisci play an essential role in maintaining normal pain-free function of the knee. While there are decades of MRI literature on the tears involving the meniscus body and horns, there is now a surge in knowledge regarding injuries at the meniscus roots and periphery. The authors briefly highlight new insights into meniscus anatomy and then summarize recent developments in the understanding of meniscus injuries that matter, emphasizing meniscus injuries at the root and peripheral (eg, ramp) regions that may be missed easily at MRI and arthroscopy. Root and ramp tears are important to diagnose because they may be amenable to repair. However, if these tears are left untreated, ongoing pain and accelerated cartilage degeneration may ensue. The posterior roots of the medial and lateral menisci are most commonly affected by injury, and each of these injuries is associated with distinctive clinical profiles, MRI findings, and tear patterns. Specific diagnostic pitfalls can make the roots challenging to evaluate, including MRI artifacts and anatomic variations. As with root tears, MRI interpretation and orthopedic treatment have important differences for injuries at the medial versus lateral meniscus (LM) periphery (located at or near the meniscocapsular junction). Medially, ramp lesions typically occur in the setting of an anterior cruciate ligament rupture and are generally classified into five patterns. Laterally, the meniscocapsular junction may be injured in association with tibial plateau fractures, but disruption of the popliteomeniscal fascicles may also result in a hypermobile LM. Updated knowledge of the meniscus root and ramp tears is crucial in optimizing diagnostic imaging before repair and understanding the clinical repercussions. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available in the Online Learning Center.

Patellofemoral pain and instability are common indications for imaging that are encountered in everyday practice. The authors comprehensively review key aspects of patellofemoral instability pertinent to radiologists that can be seen before the onset of osteoarthritis, highlighting the anatomy, clinical evaluation, diagnostic imaging, and treatment. Regarding the anatomy, the medial patellofemoral ligament (MPFL) is the primary static soft-tissue restraint to lateral patellar displacement and is commonly reconstructed surgically in patients with MPFL dysfunction and patellar instability. Osteoarticular abnormalities that predispose individuals to patellar instability include patellar malalignment, trochlear dysplasia, and tibial tubercle lateralization. Clinically, patients with patellar instability may be divided into two broad groups with imaging findings that sometimes overlap: patients with a history of overt patellar instability after a traumatic event (eg, dislocation, subluxation) and patients without such a history. In terms of imaging, radiography is generally the initial examination of choice, and MRI is the most common cross-sectional examination performed preoperatively. For all imaging techniques, there has been a proliferation of published radiologic measurement methods. The authors summarize the most common validated measurements for patellar malalignment, trochlear dysplasia, and tibial tubercle lateralization. Given that static imaging is inherently limited in the evaluation of patellar motion, dynamic imaging with US, CT, or MRI may be requested by some surgeons. The primary treatment strategy for patellofemoral pain is conservative. Surgical treatment options include MPFL reconstruction with or without osseous corrections such as trochleoplasty and tibial tubercle osteotomy. Postoperative complications evaluated at imaging include patellar fracture, graft failure, graft malposition, and medial patellar subluxation. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Survival analyses are a powerful statistical tool used to analyse data when the outcome of interest involves the time until an event. There is an array of models fit for this goal; however, there are subtle differences in assumptions, as well as a number of pitfalls, that can lead to biased results if researchers are unaware of the subtleties. As larger amounts of data become available, and more survival analyses are published every year, it is important that healthcare professionals understand how to evaluate these models and apply them into their practice. Therefore, the purpose of this study was to present an overview of survival analyses, including required assumptions and important pitfalls, as well as examples of their use within orthopaedic surgery., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)