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.

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.

Rosiglitazone induces adipogenesis of both marrow and periosteum derived mesenchymal stem cells during endochondral fracture healing.

BACKGROUND: Type 2 diabetes mellitus (T2DM) afflicts about six percent of the global population, and these patients suffer from a two-fold increased fracture risk. Thiazolidinediones (TZDs), including rosiglitazone, are commonly used medications in T2DM because they have a low incidence of monotherapy failure. It is known that rosiglitazone is associated with secondary osteoporosis, further increasing the fracture risk in an already susceptible population. However, it is not yet understood how rosiglitazone impacts endochondral bone healing after fracture. The aim of this study is to elucidate how rosiglitazone treatment impacts endochondral fracture healing, and how rosiglitazone influences the differentiation of skeletal stem and progenitor cells from the bone marrow and the periosteum. METHODS: An in-vivo mouse femur fracture model was employed to evaluate differences in fracture healing between mice treated with and without rosiglitazone chow. Fracture healing was assessed with histology and micro computed tomography (µCT). In-vitro assays utilized isolated mouse bone marrow stromal cells and periosteal cells to investigate how rosiglitazone impacts the osteogenic capability and adipogenicity of these cells. RESULTS: The in-vivo mouse femur fracture model showed that fracture callus in mice treated with rosiglitazone had significantly more adipose content than those of control mice that did not receive rosiglitazone. In addition, µCT analysis showed that rosiglitazone treated mice had significantly greater bone volume, but overall greater porosity when compared to control mice. In-vitro experimentation showed significantly less osteogenesis and more adipogenesis in bone marrow derived progenitor cells that were cultured in osteogenic media. In addition, rosiglitazone treatment alone caused significant increases in adipogenesis in both bone marrow and periosteum derived cells. CONCLUSION: Rosiglitazone impairs endochondral fracture healing in mice by increasing adipogenesis and decreasing osteogenesis of both bone marrow and periosteum derived skeletal progenitor cells.

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.

The utility of routine cultures, cell count, and crystal evaluation of aspirate from aseptic olecranon bursitis.

Background: Aspiration of the olecranon bursa is a treatment option for acute olecranon bursitis (OB). Typically, the aspirate is sent for microbiologic analysis, cell count, and crystal analysis. This study investigates the utility of fluid aspirate analysis from patients with clinically diagnosed aseptic OB. Methods: In this prospective study (IRB #i20-00986), patients presenting with acute aseptic OB were treated with aspiration as standard of care. Patients consented to participate in this study via phone. Patients with suspected infectious bursitis, open draining wound, and chronic OB were excluded. The aspirate was sent out for routine microbiologic analysis (aerobic and anaerobic cultures and Gram staining) and fluid analyses, including cell count with differential and crystal analysis. Nucleated and differential cell count was reported as absolute numbers per cubic millimeter and percentage, respectively. Compression wrap was applied after OB aspiration, and patients were asked to ice and take anti-inflammatory medications. Clinical follow-up was done after 6 weeks and at 3 months for resolution vs. recurrence of symptoms, and the mean time to resolution was reported. Results: A total of 26 patients (28 cases) with aseptic OB were enrolled in this study. Two patients had bilateral OB. The mean time to aspiration after the onset of symptoms was 26.4 days. One patient had recurrence of swelling after the first aspiration and underwent repeat bursa aspiration. No organisms were isolated or reported on Gram staining on any of the aspirate samples. Two aspirates were reported positive for calcium pyrophosphate dihydrate crystals. No patient had monosodium urate crystals. All patients had resolution of swelling and symptoms without the development of postaspiration infection. Conclusions: This study demonstrates limited clinical utility of routine microbiologic analysis (cell count, microbiologic, and crystal evaluation) of fluid aspirate from clinically diagnosed aseptic OB. Although 7% of fluid aspirates were positive for calcium pyrophosphate dihydrate crystals, it did not change the overall 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.

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.

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.

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.

Incidence of Chondral and Osteochondral Lesions in Ankle Fracture Patients Identified With Ankle Arthroscopy Following Rotational Ankle Fracture: A Systematic Review.

A systematic literature search was performed using the PubMed, MEDLINE, and the Cochrane Library databases according to the Preferred Reporting Items for Systematic review and Meta-Analyses guidelines on May 20, 2019. The keywords used were: ankle, distal tibia, distal fibula, fracture, arthroscopic, cartilage, and chondral. The objective of this study is to systematically review the characterization of intra-articular chondral injuries of the talus, tibial plafond, medial malleolus, and lateral malleolus in patients who undergo ankle arthroscopy following ankle fracture. Studies evaluating the incidence of chondral lesions at the time of arthroscopy for ankle fractures within any timeframe were included. The incidence of intra-articular chondral lesions was recorded, the location within the ankle, ankle fracture type, time of arthroscopy, characterization of chondral injury, complications, and outcome if available. Fifteen studies with 1355 ankle fractures were included. About 738 demonstrated evidence of chondral or osteochondral lesion (54.5%). Statistical analyses were carried out with statistical software package SPSS 24.0 (SPSS, Chicago, IL). We compared 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 < .05 was considered statistically significant. We found a high incidence of intra-articular chondral lesion in the setting of ankle fractures as demonstrated by arthroscopy.

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.

Anesthesia in Total Shoulder Arthroplasty: A Systematic Review and Meta-Analysis.

¼: 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. ¼: Infiltration of the shoulder with local anesthetics offers no additional benefits compared with single-shot or continuous brachial plexus blocks for shoulder arthroplasty. ¼: 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. ¼: 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. ¼: Perioperative dexamethasone administration improves postoperative pain control, decreases perioperative opioid requirements, and reduces postoperative nausea.