Cyclin F-Mediated Degradation of SLBP Limits H2A.X Accumulation and Apoptosis upon Genotoxic Stress in G2.

SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an atypical CY motif, and mutation of this motif prevents SLBP degradation in G2. Expression of an SLBP stable mutant results in increased loading of H2AFX mRNA onto polyribosomes, resulting in increased expression of H2A.X (encoded by H2AFX). Upon genotoxic stress in G2, high levels of H2A.X lead to persistent γH2A.X signaling, high levels of H2A.X phosphorylated on Tyr142, high levels of p53, and induction of apoptosis. We propose that cyclin F co-evolved with the appearance of stem-loops in vertebrate H2AFX mRNA to mediate SLBP degradation, thereby limiting H2A.X synthesis and cell death upon genotoxic stress.

Non-psychoactive Cannabidiol Prevents Osteoporosis in an Animal Model and Increases Cell Viability, Proliferation, and Osteogenic Gene Expression in Human Skeletal Stem and Progenitor Cells.

Cannabidiol (CBD), the non-psychoactive component of the Cannabis sativa plant, is marketed as a potential therapeutic agent and has been studied for its roles in reducing inflammation and managing neuropathic pain. Some studies have reported that CB1 and CB2 receptor activation can attenuate and reverse bone loss in experimental animal models. Despite this, little is known about the impact of CBD on fracture healing. We investigated the effects of CBD in vitro using human osteoprogenitor cells and in vivo via murine femur fracture and osteoporosis models. In vitro mesenchymal stem cells were treated with increasing concentrations of crystalized pharmaceutical grade CBD or vehicle solution. Cell viability and proliferation were significantly increased in cells treated with CBD compared to vehicle control. Osteocalcin expression was also significantly higher in the CBD-treated human stem cells compared to vehicle control. In vivo the effect of CBD on bone mineral density and fracture healing in mice was examined using a two-phase experimental approach. Fluoxetine was used for pharmacologic induction of osteoporosis and surgical oophorectomy (OVX) was used for hormonal induction of osteoporosis. X-ray and microCT analysis showed that CBD prevented both fluoxetine- and OVX-induced osteoporosis. We found that while OVX resulted in delayed bone healing in control mice, CBD-pretreated mice exhibited normal bone healing. Collectively these in vitro and in vivo findings suggest that CBD exerts cell-specific effects which can be exploited to enhance bone metabolism. These findings also indicate that CBD usage in an osteoporotic population may positively impact bone morphology, warranting further research.

Transosseous tunnels versus suture anchors for the repair of acute quadriceps and patellar tendon ruptures: A systematic review and meta-analysis of biomechanical studies.

BACKGROUND: Multiple techniques have been developed for the repair of acute quadriceps and patellar tendon ruptures with the goal of optimizing clinical outcomes while minimizing complications and costs. The purpose of this study was to evaluate the biomechanical properties of transosseous tunnels and suture anchors for the repair of quadriceps and patellar tendon ruptures. METHODS: A systematic review of the PubMed and Embase databases was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using specific search terms and eligibility criteria. Meta-analysis was performed by fixed-effects models for studies of low heterogeneity (I2 <25%) and random-effects models for studies of moderate to high heterogeneity (I2 ≥25%). RESULTS: A total of 392 studies were identified from the initial literature search with 7 studies meeting the eligibility criteria for quadriceps tendon repair and 8 studies meeting the eligibility criteria for patellar tendon repair. Based on the random-effects model for total gap formation and load to failure for quadriceps tendon repair, the mean difference was 8.88 mm (95% CI, -8.31 mm to 26.06 mm; p = 0.31) in favor of a larger gap with transosseous tunnels and -117.25N (95%CI, -242.73N to 8.23N; p = 0.07) in favor of a larger load to failure with suture anchors. A similar analysis for patellar tendon repair demonstrated a mean difference of 2.86 mm (95% CI, 1.08 mm to 4.64 mm; p = 0.002) in favor of a larger gap with transosseous tunnels and -56.34N (95% CI, -226.75 to 114.07N; p = 0.52) in favor of a larger load to failure with suture anchor repair. CONCLUSIONS: Transosseous tunnels are biomechanically similar to suture anchors for quadriceps tendon repair. Patellar tendon repair may benefit from reduced gap formation after cycling with suture anchor repair, but the load to failure for both techniques is biomechanically similar. Additional studies are necessary to evaluate these and alternative repair techniques. LEVEL OF EVIDENCE: Systematic review and meta-analysis of biomechanical studies, Level V.

Iliac Crest and Distal Radius Autografts Exhibit Distinct Cell-Intrinsic Functional Differences.

PURPOSE: Autologous bone grafts demonstrate osteoconductive, osteoinductive, and osteogenic properties. Hand surgeons commonly augment surgical fixation with autografts to promote fracture healing. This study compared the intrinsic stem cell-like properties of 2 commonly used autograft sources in hand surgery: the iliac crest and distal radius. METHODS: A total of 9 subjects who received an iliac crest bone graft and distal radius bone graft harvest as a part of the standard care of distal radius malunion or nonunion correction or scaphoid nonunion open reduction and internal fixation were enrolled in the study. Cells were isolated by serial collagenase digestion and subjected to fibroblast colony-forming units, osteogenesis, and adipogenesis assays. The expression levels of genes involved in osteogenesis and adipogenesis were confirmed using quantitative polymerase chain reaction. RESULTS: The cells isolated from the iliac crest bone graft compared with those isolated from the distal radius bone graft demonstrated significantly higher mean fibroblast colony-forming unit efficiency; increased osteogenesis, as measured using alizarin red quantification; increased adipogenesis, as measured using oil red O quantification; and higher expression levels of genes involved in osteogenesis and adipogenesis under the respective differentiation conditions. CONCLUSIONS: The cells isolated from the iliac crest bone graft demonstrated a higher fibroblast colony-forming unit capacity and an increased capability to undergo both osteogenesis and adipogenesis. CLINICAL RELEVANCE: Limited evidence exists comparing the intrinsic stem cell-like properties of the iliac crest and distal radius despite the widespread use of each source in hand and wrist surgery. The information from this investigation may assist hand and wrist surgeons with the selection of a source of autograft.

Dual Mobility Total Hip Arthroplasty in the United States: A Review of Current and Novel Designs.

Dual mobility constructs have become an increasingly popular option for primary and revision total hip arthroplasty. Two monoblock implants and three modular implants are available for use in the United States. Although short- and mid-term outcome data have been positive overall for these systems, each construct has unique features that the orthopaedic surgeon might consider when selecting the appropriate implant for his or her patient. In this review article, we discuss the design specifications and published literature for each dual mobility system and organize this information into a concise resource that can be easily referenced during preoperative planning.

Cytokine Receptor-like Factor 1 (CRLF1) and Its Role in Osteochondral Repair.

BACKGROUND: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. METHODS: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. RESULTS: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. CONCLUSION: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Expanded Demographics for the Tillaux Fracture in Patients Receiving Feminizing Hormone Therapy A Case Report.

We present the case of a transgender female patient who had been undergoing feminizing hormone therapy for several years and sustained a Tillaux fracture despite being older than the expected age range for females with this injury pattern. Despite work focused on understanding physeal closure, the molecular signals governing this phenomenon remain incompletely described. This case study illustrates that physeal closure may be delayed in patients undergoing sex hormone therapy with associated transitional fractures possibly occurring later than would be expected for the transitional gender. Additional work is necessary to clarify the direct effect of sex hormonal therapy on physeal homeostasis.

Outcomes of Autologous Osteochondral Transplantation With and Without Extracellular Matrix Cartilage Allograft Augmentation for Osteochondral Lesions of the Talus.

BACKGROUND: Autologous osteochondral transplantation (AOT) using a cylindrical graft in the treatment of osteochondral lesions of the talus (OLTs) is typically indicated for patients with larger lesions. However, with lesions that are irregular in shape, the AOT graft may not completely replace the lesion. For these lesions, we utilize extracellular matrix cartilage allograft (EMCA) augmentation in AOT to act as a physiologic grout at the host-graft interface. PURPOSE: To determine if the combination of EMCA with concentrated bone marrow aspirate (CBMA) would improve integration of the host-graft interface and subsequently reduce postoperative cyst formation after AOT. It was also hypothesized that EMCA in conjunction with CBMA would demonstrate improved MOCART (magnetic resonance observation of cartilage repair tissue) scores and functional outcome scores at a minimum 2 years after surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective analysis was performed comparing patients treated with AOT/CBMA alone and AOT with CBMA/EMCA. Clinical outcomes were evaluated with the Foot and Ankle Outcome Score. Magnetic resonance imaging appearance was evaluated with the use of the MOCART (magnetic resonance observation of cartilage repair tissue) score. Cyst formation was also evaluated on postoperative magnetic resonance imaging. RESULTS: A total of 26 patients were included in the AOT + CBMA/EMCA group (10 male, 16 female), and 34 patients were included in the AOT/CBMA group (17 male, 17 female). The mean Foot and Ankle Outcome Score significantly improved in both groups (P < .001) across all subscales (symptoms, pain, activities of daily living, sports activities, and quality of life), but there was no significant difference between groups at final follow-up. There was no significant difference in mean MOCART scores between the groups (P = .118). In the AOT/CBMA group, 3 patients (8.8%) complained of knee pain, and 1 (2.9%) required additional surgery (hardware removal). In the AOT + CBMA/EMCA group, 2 patients (7.7%) complained of knee pain, and 6 patients (23%) required additional surgery (3 hardware removals and 3 arthroscopic debridements of scar tissue in the ankle). CONCLUSION: We found that while EMCA with CBMA has benefit in regeneration and repair of OLT treated with bone marrow stimulation, there appears to be little benefit of EMCA over CBMA alone as a physiologic grout at the graft-host interface in OLT treated with AOT.

Operative Treatment of Proximal Humeral Fractures with Reverse Total Shoulder Arthroplasty in Patients ≥65 Years Old: A Critical Analysis Review.

¼: The majority of proximal humeral fractures (PHFs) in patients who are ≥65 years of age are treated nonoperatively, but certain complex fracture patterns benefit from surgical intervention. However, there continues to be debate regarding the indications for surgery and the optimal surgical treatment (repair versus replacement) in this population. ¼: Reverse total shoulder arthroplasty (RTSA) has grown in popularity for surgical treatment of fracture-dislocations and displaced complex PHFs in patients who are ≥65 years of age; it has definite advantages over surgical repair and hemiarthroplasty, but this finding requires additional higher-quality evidence. ¼: RTSA provides early pain relief and return of shoulder function as well as predictable elevation above shoulder level in the forward plane, but the indications for and understanding of the effect of timing on RTSA after a PHF continue to evolve. ¼: RTSA for an acute PHF is indicated in patients who are ≥65 years of age with 3- and 4-part fracture-dislocations, head-split fractures, and severely displaced fractures, and is an option in patients who are not able to tolerate nonoperative treatment of severely displaced 3- and 4-part fractures. ¼: RTSA is also indicated as a salvage operation for PHFs that have failed initial surgical repair (i.e., fixation failure, implant failure, rotator cuff failure, or osteonecrosis) and is an option for symptomatic nonunion or malunion after nonoperative treatment.

Primary Quadriceps Tendon Suture Anchor Repair: Case Presentation and Surgical Technique.

SUMMARY: This case presentation described a technique for repairing an acute quadriceps tendon rupture with suture anchors. The patient was a 51-year-old man who sustained an acute quadriceps tendon rupture after a fall. We used a midline incision over the quadriceps tendon and muscle. The tendon was found to be completely avulsed from the superior border of the patella. Three suture anchors were used to re-approximate the quadriceps tendon to the patella and additional sutures were used to repair the medial and lateral patellar retinacula. The patient had excellent range of motion at his 6-week follow-up appointment after the procedure.

Posterior Hindfoot Needle Endoscopy in the Office Setting.

Posterior hindfoot disorders encompass a spectrum of bony, cartilaginous, and soft-tissue pathology. Traditional open surgical techniques have been increasingly replaced by less-invasive arthroscopic and endoscopic approaches. Recent innovations such as the advent of the needle arthroscope continue to push the boundary of minimally invasive interventions. This Technical Note highlights our technique for posterior hindfoot needle endoscopy for common posterior hindfoot pathologies in the wide-awake office setting, including indications, advantages, and technical pearls.

Achilles Paratenon Needle Tendoscopy in the Office Setting.

Achilles tendinopathy is a common inflammatory condition of the Achilles tendon prevalent in the athletic population in which patients present with pain, swelling, and reduced performance exacerbated by physical activity. Operative intervention using either open or percutaneous approaches has traditionally been performed after failure of nonoperative treatment, but less invasive modalities that include endoscopic approaches have been increasingly used. This Technical Note highlights our technique for Achilles paratenon needle tendoscopy in the wide-awake office setting, with accompanying indications for use, advantages, and technical pearls.

In-Office Needle Arthroscopy for Anterior Ankle Impingement.

Anterior ankle impingement is a common cause of chronic ankle pain characterized by altered joint mechanics with considerable deficits in range of motion. The benefits of in-office nano arthroscopy (IONA) include the ability to diagnosis and treat anterior ankle impingement, quicker patient recovery, reduced cost, and improved patient satisfaction. The purpose of this technical report is to describe the technique for performing in-office nano arthroscopy for anterior ankle impingement, with special consideration of the technique for obtaining adequate local anesthesia, proper indications, adequate visualization, and the advantages of performing these procedures in the office rather than the operating room.

In-Office Needle Tendoscopy of the Tibialis Posterior Tendon with Concomitant Intervention.

Tendoscopy has been recognized to be a useful technique in the diagnosis and treatment of early tibialis posterior tendon (TPT) dysfunction. Although open surgical procedures for advanced TPT disease have led to excellent outcomes, disagreement persists concerning the correct management algorithm for early TPT dysfunction. Recent developments in needle tendoscopy have provided a minimally invasive option for direct evaluation and intervention throughout the forefoot, midfoot, and hindfoot. The goal of this manuscript is to describe the technique for performing in-office needle tendoscopy targeting the TPT with a discussion of indications and opportunities afforded by an in-office procedure over the traditional operating room suite.

In-Office Needle Tendoscopy of the Peroneal Tendons.

In-office needle tendoscopy (IONT) can be used for the diagnosis and treatment of several peroneal tendon pathologies including peroneal tendon tendinopathy, tears, and instability. Benefits of IONT for peroneal tendon disorders include the ability to dynamically evaluate peroneal tendon stability, quicker patient recovery, reduced cost, and improved patient satisfaction. Several studies have suggested that tendoscopic treatment may avoid several complications related to open treatment of peroneal tendon pathologies, including scar formation and groove stenosis. The purpose of the present report is to describe the technique for performing IONT for common peroneal tendon pathologies. This Technical Note describes the techniques for obtaining adequate anesthesia and performing IONT, indications, and advantages of performing these procedures in the office rather than in the operating room.

Needle Arthroscopy Cheilectomy for Hallux Rigidus in the Office Setting.

Hallux rigidus is a progressive degenerative process of the first metatarsophalangeal joint characterized by altered joint mechanics and formation of dorsal osteophytes. Cheilectomy is the preferred operative intervention at early stages. Technologic advances, patient preference, and cost considerations combine to stimulate the development of minimally invasive and in-office interventions. This Technical Note highlights our technique for needle arthroscopy cheilectomy for hallux rigidus, which can be used either in the operating room or in the wide-awake office setting.

Anterior Talofibular Ligament Augmentation With Internal Brace in the Office Setting.

The anterior talofibular ligament (ATFL) is the most frequently injured lateral ligament of the ankle, and up to 20% of patients with ankle sprains may require surgical intervention to correct chronic lateral ankle instability. There has been increased interest in arthroscopic lateral ankle ligament repair techniques to minimize postoperative pain and expedite recovery. Additionally, the use of suture-tape augmentation may allow for improved recovery in those with ATFL reconstruction. The goal of this Technical Note is to describe the steps to performing in-office needle arthroscopy using suture tape as an internal brace for an ATFL deficient ankle. We also include an accompanying discussion on indications and opportunities afforded by an in-office procedure over the traditional operating room suite.

Improved Clinical Outcomes and Patient Satisfaction of In-Office Needle Arthroscopy for the Treatment of Posterior Ankle Impingement.

Purpose: To investigate the short-term clinical outcomes and satisfaction for the first set of patients at our institution receiving in-office needle arthroscopy (IONA) for the treatment of posterior ankle impingement syndrome (PAIS). Methods: A retrospective cohort study was conducted to evaluate patients who underwent IONA for PAIS between January 2019 and January 2021. Clinical outcomes were evaluated using the Foot and Ankle Outcome Score (FAOS) and Patient-Reported Outcomes Measurement Information System Pain Interference, and Pain Intensity scores. Patient satisfaction was measured at the final follow-up visit with a 5-point Likert scale. The Wilcoxon signed-rank test was performed to compare preoperative and postoperative outcome scores. Results: Ten patients (4 male and 6 female) with a mean age of 41.9 ± 15.5 years (range, 24-66 years) were included in the study. The mean follow-up time was 13.3 ± 2.9 months (range, 11-17 months). All mean preoperative FAOS scores demonstrated improvement after IONA, including FAOS symptoms (71.48 ± 10.3 to 80.3 ± 12.6), pain (69.3 ± 11.0 to 78.2 ± 13.9), activities of daily living (61.7 ± 8.8 to 77.93 ± 11.4), sports activities (55.6 ± 12.7 to 76.0 ± 13.6), and quality of life (46.6 ± 9.2 to 71.1 ± 12.1). There were 7 patients who participated in sports activities before the IONA procedure. Within this group, all patients returned to play at a median time of 4.1 weeks (range, 1-14 weeks). The median time to return to work was 3.4 ± 5.3 days. Patients reported an overall positive IONA experience with a mean rating scale of 9.5 ± 1.5 (range, 5-10). Conclusions: The current study demonstrates that IONA treatment of PAIS results in significant pain reduction, a low complication rate, and excellent patient-reported outcomes. In addition, IONA for PAIS leads to high patient satisfaction with a significant willingness to undergo the same procedure again. Level of Evidence: IV, therapeutic case series.

Mask-Related Glasses Fogging: A Predisposing Mechanism of Falls during the COVID-19 Pandemic.

Fogging is a relatively infrequent, yet annoying, issue encountered by individuals who wear glasses. With the arrival of COVID-19, glasses fogging is more common due to the ubiquitous use of face masks. Individuals are stuck wrestling between leaving their mask off or trying to navigate their day-to-day lives with fogged glasses and risk falling. We report a case of an olecranon fracture sustained due to reduced visibility secondary to mask-related fogging during the COVID-19 pandemic. The recommendations included here will provide health care providers with the necessary information to educate patients regarding prevention of mask-related glass fogging.

Arthroscopic Debridement and Autologous Micronized Adipose Tissue Injection in the Treatment of Advanced-Stage Posttraumatic Osteoarthritis of the Ankle.

OBJECTIVE: To evaluate the effect of intra-articular injection of autologous micronized adipose tissue (MAT) with ankle arthroscopic debridement in patients with advanced-stage posttraumatic osteoarthritis (PTOA) of ankle. DESIGN: A retrospective cohort study investigating patients treated with arthroscopic debridement and autologous MAT injection for ankle PTOA was performed. Patients with Kellgren-Lawrence (KL) grade 3 to 4 were included. Visual analogue scale (VAS), Foot and Ankle Outcome Scores (FAOS), and patient satisfaction were evaluated. RESULTS: A total of 19 patients (19 ankles) were included (KL grade 3, 8 patients; grade 4, 11 patients). At a mean follow-up time of 14.3 months (range, 7-23 months), the mean FAOS subscales for pain and quality of life significantly increased from 48.8 and 20.1 preoperatively to 61.1 and 30.1 (P = 0.029 and 0.048, respectively). The mean VAS score significantly improved from 6.1 to 3.8 (P = 0.003) at final follow-up. A total of 10.5% (2/19) of patients were very satisfied, 31.6% (6/19) satisfied, 26.3% (5/19) neutral, 21.1% (4/19) unsatisfied, and 10.5% (2/19) very unsatisfied with their outcomes. The overall FAOS score demonstrated a significant difference in pre- to postoperative change with 14.8 for KL grade 3 and 5.9 for KL grade 4 (P = 0.048). CONCLUSIONS: Autologous MAT injection is a safe and potentially beneficial procedure for advanced-stage ankle PTOA as an adjunct to arthroscopic debridement, although more than one-third of patients were unsatisfied with the procedure. This procedure may be more beneficial for KL grade 3 patients than grade 4 patients. However, future investigations are necessary to define the role of MAT for ankle PTOA.