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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.

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.

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.

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.

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.

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.

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.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.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.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.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.

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.

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.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.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.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.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.

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.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 (IA 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.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.Systematic review and meta-analysis of biomechanical studies, Level V.

Paul W. Lapidus' work has formed the foundation of modern foot and ankle surgery. Variations of his popularizedtechnique, the Lapidus procedure, remain in regular usetoday for the management and correction of hallux valgus.We revisit Dr. Lapidus' career and accomplishments withan emphasis on his importance to the expanding divisionof foot and ankle surgery at the Hospital for Joint Diseases.

» For shoulder arthroplasty, regional anesthesia is safer when compared with general anesthesia. There is insufficient evidence to demonstrate the superiority of regional anesthesia with respect to pulmonary complications and hospital length of stay. » Infiltration of the shoulder with local anesthetics offers no additional benefits compared with single-shot or continuous brachial plexus blocks for shoulder arthroplasty. » There is high-quality evidence (Level I) demonstrating lower pain scores and lower perioperative opioid requirements after a continuous peripheral nerve block compared with a single-shot nerve block. However, catheter dislodgment and logistical issues with catheter insertion are impediments to the widespread usage of a continuous nerve block with an indwelling catheter. » Liposomal bupivacaine is comparable with non-liposomal local anesthetic agents with respect to pain relief, the opioid-sparing effect, and adverse effects in the first 48 hours after total shoulder arthroplasty. » Perioperative dexamethasone administration improves postoperative pain control, decreases perioperative opioid requirements, and reduces postoperative nausea.

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.

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.

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.

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.

Objective: Patients frequently use the internet as a source to obtain health information. The purpose of this study was to evaluate the quality and readability of online resources on the diagnosis and treatment of ankle osteochondral lesions (OCLs). Design: Three search terms (“ankle cartilage defect,” “cartilage injury,” “ankle cartilage damage”) were entered into 3 search engines (Google, Yahoo, and Bing). The first 20 websites from each search was collected excluding websites intended for health care providers. The quality of the websites were evaluated using the DISCERN instrument, JAMA benchmark, and a Quality rating criteria specific to ankle OCL. The readability was assessed using Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL). Statistical analysis was performed using one-way analysis of variance. Results: A total of 41 websites were reviewed. The mean quality ratings were poor across the assessment tools: DISCERN = 38.5 ± 9.0 (range, 23.7-56.7) out of 80; JAMA = 1.0 ± 1.1 (range, 0-3.3) out of 4; and Quality rating criteria = 11.3 ± 4.6 (range, 4-20.7) out of 24. The mean FRE and FKGL were 40.7 ± 32.0 (range, −152.3 to 60.2) and 13.5 ± 10.8 (range, 8.4-80.7), respectively; higher than the recommended reading level for patients (fifth grade). Conclusions: The quality and readability of credible sources for ankle OCL were poor, which could lead to misinformation. This study should guide the improvement of online information on ankle OCL.

Introduction: Microfracture has been widely published as a treatment for osteochondral lesions of the talus (OLT). Little is known about the outcome predictors following microfracture for smaller sized OLT. Objectives: This study sought to define the outcome predictors for small OLT treated with microfracture and concentrated bone marrow aspirate (CBMA). Our hypothesis was that lesion uncontainment and the presence of cysts were predictors of poor outcomes following microfracture with CBMA for OLT. Methods: A retrospective cohort study investigating patients who received microfracture for OLT (

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.

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.

Background: Biological adjuvants are used after a musculoskeletal injury to improve healing, decrease inflammation, and restore joint homeostasis. Work on 1 such adjuvant, platelet-rich plasma (PRP), has suggested a positive effect when introduced during cartilage repair. However, it remains unknown whether healing osteochondral injuries benefit from serial PRP injections. Purpose: To evaluate the effects of serial PRP injections versus a single PRP injection on reparative cartilaginous tissue, subchondral bone remodeling, and the expression of inflammatory cytokines in joint synovium. Study Design: Controlled laboratory study. Methods: A total of 48 New Zealand White rabbits were randomly assigned to receive 1 (1P), 2 (2P), or 3 (3P) PRP injections. Cylindrical full-thickness cartilage defects (2.9 × 2.9 mm) with microdrillings (0.6-mm diameter) were created on the medial condyles of both knees. PRP was injected into the right knee after closure (groups 1P, 2P, and 3P), at 2 weeks after surgery (groups 2P and 3P), and at 4 weeks after surgery (group 3P). The left knees did not receive any PRP injections. A total of 6 rabbits in each group were euthanized at 3, 6, and 12 weeks postoperatively. Cartilage repair tissue was assessed using the Goebel macroscopic and modified International Cartilage Regeneration & Joint Preservation Society (ICRS) histological scoring systems. Subchondral bone remodeling was evaluated by micro–computed tomography analysis (micro-CT). Inflammatory cytokine levels were assessed by quantitative polymerase chain reaction. Results: No significant differences were found for the mean macroscopic score between the PRP groups at 12 weeks (control, 6.1 ± 3.3; group 1P, 3.4 ± 2.7; group 2P, 4.2 ± 2.9; group 3P, 0.7 ± 1.5). All PRP groups had a significantly higher mean modified ICRS histological score compared with the control group, but no significant difference was found among the PRP groups. No significant differences were seen in outcomes for the tested micro-CT parameters or cytokine expression levels. Conclusion: Serial PRP injections conferred no apparent advantage over single injections according to evaluations of the macroscopic and histological appearance of the cartilaginous tissue, subchondral bone healing, and inflammatory cytokine expression levels in the synovium. Clinical Relevance: The use of PRP as a biological adjuvant to bone marrow stimulation for osteochondral lesions has the potential to enhance the quality of regenerative cartilaginous tissue. We recommend only a single PRP injection if the use of PRP is indicated by the operating surgeon as an adjuvant therapy for osteochondral lesions.

Category: Hindfoot; Ankle; Ankle Arthritis; Basic Sciences/Biologics; Trauma Introduction/Purpose: The purpose of this study was to evaluate the efficacy of biological adjuvants in hindfoot arthrodesis. 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. Assessment of evidence was three-fold: level of evidence by criteria published by The Journal of Bone & Joint Surgery, quality of evidence by the Newcastle-Ottawa scale and conflicts of interest. Meta-analysis was performed by fixed-effects models for studies of low heterogeneity (I2 =25%). Results: Hindfeet totaled 1579 patients as protocol and 1503 patients per protocol. Final reported mean follow-up ranged from 2.8 months to 43 months. Twelve of the 17 included studies were comprised of patients with comorbidities associated with reduced healing capacity. Based on the random-effects model for non-union rates for autograft versus allograft, the risk ratio was 0.82 (95% CI, 0.13 to 5.21; I2 = 56%; p = 0.83) in favour of lower non-union rates for autograft and for autograft versus rhPDGF/ß-TCP, the risk ratio was 0.90 (95% CI, 0.74 to 1.10; I2 = 59%; p = 0.30) in favour of lower non-union rates for rhPDGF/ß-TCP. Conclusion: There is a lack of data to support the meaningful use of biological adjuvants compared to autograft/allograft for hindfoot arthrodesis. The meta-analysis favoured the use of autograft when compared to allograft, but favoured rhPDGF/ß-TCP instead when compared to autograft in the short-term follow-up.

// Miguel F. Segura 1, 2, 3 , Luz Jubierre 3 , SiDe Li 4 , Aroa Soriano 3 , Lisa Koetz 1, 2 , Avital Gaziel-Sovran 1, 2 , Marc Masanas 3 , Kevin Kleffman 1, 2 , John F. Dankert 1, 2 , Martin J Walsh 4 , Eva Hernando 1, 2 1 Department of Pathology, New York University School of Medicine, New York, NY, USA 2 Interdisciplinary Melanoma Cooperative Group, New York University Perlmutter Cancer Institute, NYU School of Medicine, New York, NY, USA 3 Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute (VHIR)-UAB, Barcelona, Spain 4 Departments of Structural and Chemical Biology, Genetics and Genomic Sciences and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA Correspondence to: Miguel F. Segura, email: miguel.segura@vhir.org Eva Hernando, email: eva.hernando@nyumc.org Keywords: microRNA, embryonic stem cells, melanoma, miR-183~96~182 cluster, KLF4 Received: June 30, 2016 Accepted: February 06, 2017 Published: February 17, 2017 ABSTRACT MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that post-transcriptionally control the translation and stability of target mRNAs in a sequence-dependent manner. MiRNAs are essential for key cellular processes including proliferation, differentiation, cell death and metabolism, among others. Consequently, alterations of miRNA expression contribute to developmental defects and a myriad of diseases. The expression of miRNAs can be altered by several mechanisms including gene copy number alterations, aberrant DNA methylation, defects of the miRNA processing machinery or unscheduled expression of transcription factors. In this work, we sought to analyze the regulation of the miR-182 cluster, located at the 7q32 locus, which encodes three different miRNAs that are abundantly expressed in human embryonic stem cells and de-regulated in cancer. We have found that the Kruppel-like factor 4 (KLF4) directly regulates miR-182 cluster expression in human embryonic stem cells (hESCs) and in melanoma tumors, in which the miR-182 cluster is highly expressed and has a pro-metastatic role. Furthermore, higher KLF4 expression was found to be associated with metastatic progression and poor patient outcome. Loss of function experiments revealed that KLF4 is required for melanoma cell maintenance. These findings provide new insights into the regulation of the miR-182 cluster expression and new opportunities for therapeutic intervention in tumors in which the KLF4-miR-182 cluster axis is deregulated.

FEM1A, FEM1B, and FEM1C are evolutionarily-conserved VHL-box proteins, the substrate recognition subunits of CUL2-RING E3 ubiquitin ligase complexes. Here, we report that FEM1 proteins are ancient regulators of Stem-Loop Binding Protein (SLBP), a conserved protein that interacts with the stem loop structure located in the 3' end of canonical histone mRNAs and functions in mRNA cleavage, translation and degradation. SLBP levels are highest during S-phase coinciding with histone synthesis. The ubiquitin ligase complex SCFcyclin F targets SLBP for degradation in G2 phase; however, the regulation of SLBP during other stages of the cell cycle is poorly understood. We provide evidence that FEM1A, FEM1B, and FEM1C interact with and mediate the degradation of SLBP. Cyclin F, FEM1A, FEM1B and FEM1C all interact with a region in SLBP's N-terminus using distinct degrons. An SLBP mutant that is unable to interact with all 4 ligases is expressed at higher levels than wild type SLBP and does not oscillate during the cell cycle. We demonstrate that orthologues of SLBP and FEM1 proteins interact in C. elegans and D. melanogaster, suggesting that the pathway is evolutionarily conserved. Furthermore, we show that FEM1 depletion in C. elegans results in the upregulation of SLBP ortholog CDL-1 in oocytes. Notably, cyclin F is absent in flies and worms, suggesting that FEM1 proteins play an important role in SLBP targeting in lower eukaryotes.

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.

Category: Ankle; Trauma Introduction/Purpose: It is controversial whether routine arthroscopy is beneficial at the time of ankle fracture fixation. This may be, in part, due to sparse information regarding the incidence of chondral injury in the setting of ankle fractures.The purpose of this study is to systematically review the incidence of chondral injures in patients with ankle fractures and to further characterize intra-articular chondral injuries of the talus, tibial plafond, medial malleolus, and lateral malleolus in patients who undergo ankle arthroscopy following an ankle fracture. Methods: The literature search was performed based on the PRISMA guidelines. Studies evaluating the incidence of chondral lesions at the time of arthroscopy for ankle fractures were included. The incidence of intraarticular chondral lesions was recorded, as well as location within the ankle, ankle fracture type, time of arthroscopy, characterization of chondral injury, complications, and outcome if available. All statistical analyses were carried out with statistical software package SPSS 24.0 (SPSS, Chicago, IL, USA). Multiple comparisons were used to compare incidence rates of chondral injury based on Weber classification, malleolar fracture type, and Lauge-Hansen classification, using Pearson chi-square test. For all analyses, p < 0.05 was considered statistically significant. Results: Fifteen studies with 1,355 ankle fractures were included. Of those ankles, 738 demonstrated evidence of chondral or osteochondral lesion (54.5%). Overall, 648 ankles had chondral lesions on the talus (47.8%), 207 ankles had lesions on the tibial plafond (15.3%), 165 has lesions of the lateral malleolus (12.2%), and 133 had lesions of the medial malleolus (9.8%). Weber C group had significantly higher incidence than Weber A group (p=0.015). Trimalleolar and isolated lateral malleolar fracture groups had significantly higher incidence of chondral injury than bimalleolar and isolated medial malleolar fracture groups (pConclusion: Our study found a high incidence of intra-articular chondral lesion in the setting of ankle fractures as demonstrated by arthroscopy, with more than half of all patients having a chondral lesion. Talar lesions were most common. This study may help direct greater attention to the Talus as a source of chondral injury particularly in higher grade fracture patterns.

Purpose:To characterize the volume and variation in orthopedic consults and surgeries that took place during a period of social distancing and pandemic.Methods:All orthopedic consults and surgeries at an urban level 1 trauma center from 3/22/20-4/30/2020 were retrospectively reviewed (the social distancing period). Data from the same dates in 2019 were reviewed for comparison. Age, gender, Score for Trauma Triage in the Geriatric and Middle Aged (STTGMA) score and injury type were queried. Operating room data collected included: type of surgery performed, inpatient or outpatient status, and if the cases were categorized as elective, trauma or infectious cases.Results:Compared to 2019, there was a 48.3% decrease in consult volume in 2020. The 2020 population was significantly older (44.0 vs 52.6 years-old, p = 0.001) and more male (65% vs 35%, p = 0.021). There were 23 COVID positive patients, 10 of which died within the collection period. Consult distribution dramatically changed, with decreases in ankle fractures, distal radius fractures and proximal humerus fractures of 76.5%, 77.4% and 55.0%, respectively. However, there was no significant difference in volume of hip, tibial shaft and femoral shaft fractures (p > 0.05). In 2020, there was a 41.4% decrease in operating room volume, no elective cases were performed, and cases were primarily trauma related.Conclusions:During a period of pandemic and social distancing, the overall volume of orthopedic consults and surgeries significantly declined. However, hip fracture volume remained unchanged. Patients presenting with orthopedic injuries were older, and at higher risk for inpatient mortality.

SummaryTo metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential, shorter time to recurrence, and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data support a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immunosuppression.