Prevalence of AAV2.5 neutralizing antibodies in synovial fluid and serum of patients with osteoarthritis.

Osteoarthritis (OA) is a leading cause of disability with no cure and only supportive therapy. Adeno-associated virus (AAV) serotype 2.5 is being used in a Phase I clinical trial to deliver the interleukin-1 receptor antagonist into knee joints with OA. Neutralizing antibodies (Nab) directed against AAV2.5, if present, could inhibit gene transfer. Here, we report the prevalence of AAV2.5 Nab in the sera and synovial fluids of patients with OA. Nab titers were measured by their ability to inhibit in vitro transduction by AAV2.5 encoding GFP. Of 44 synovial fluids from patients with mid-stage and advanced OA, 43% had undetectable Nab; 25% had low titers (<1:100), 16% had medium titers (1:100-1:1000) and 16% had high titers (>1:1000) of Nab. Titers of AAV2.5 Nabs correlated with those of AAV2, but not with those of AAV5. Serum titers of AAV2.5 Nab correlated positively with titers in synovial fluid, and were never less than the matched synovial fluid titers. These findings suggest that high titers of Nab against AAV2.5 are uncommon in the synovial fluids of patients with OA, and individuals with high synovial fluid Nab titers can be identified by measuring titers in the serum.

Ultrasound Use by Upper Extremity Surgeons in 2020: A Survey of ASSH Members.

BACKGROUND: The use of musculoskeletal ultrasound (US) among hand surgeons appears to be increasing. The purpose of this study was to determine the utilization patterns and attitudes regarding US among American Society for Surgery of the Hand (ASSH) members in 2020 as well as the changes in usage patterns since a previous survey in 2015. METHODS: In 2020, an updated and expanded 27-question survey was distributed to 4852 members of the ASSH. Questions assessed respondent demographics, training, and practice patterns, and access, utilization, training, and opinions pertaining to US. RESULTS: A total of 418 surveys (8.6%) were analyzed. Compared to 2015, there was an increase in the percentage of respondents using US for diagnostic purposes (51%-68%), as well as having personal access to US machines (43% to 58%). US use to assist in diagnosing carpal tunnel syndrome increased from 19% to 27%. The most common reason for using US was convenience and practice efficiency, while the most common reasons for not using US was no machine access. In 2020, 33% of respondents performed US-guided injections. CONCLUSIONS: Compared to 2015, the majority of responding upper extremity surgeons now have personal access to US machines. Utilization of diagnostic US appears to be increasing, and two-thirds of respondents believed that US use will continue to increase among upper extremity surgeons.

Optimization of Preoperative Anemia in Lower Limb Joint Replacement Surgery: Assessing the Rates of Allogenic Blood Transfusion and Duration of Hospital Stay.

BACKGROUND: Orthopaedic procedures such as total hip and total knee replacements carry a significant risk of postoperative anemia, necessitating allogenic blood transfusions (ABTs), and an increased hospital length of stay. AIM: Our aim was to investigate whether the implementation of a local protocol designed to detect and treat preoperative anemia resulted in reduced ABT rates and a shorter duration of length of hospital stay (LOS). METHODS: We retrospectively audited 683 patients undergoing primary hip and knee replacements. We collated data for all patients about hospital length of stay and blood transfusions received. Both descriptive statistics and univariate analysis were performed. RESULTS: Approximately 21.6% of the cohort within the study who were anemic at preoperative clinic had a significantly increased median LOS of 2 days (p < .001) and an increased packed red cell transfusion rate compared with non-anemic patients (26.1% vs. 2.21%, p < 001). However, treatment of preoperative anemia did not show any significant difference in transfusion rates compared with patients who did not receive corrective treatment. The median LOS was higher by 1 day in the treated group compared with the nontreated cohort (p = .005). CONCLUSION: There is significant evidence to suggest that preoperative anemia can increase LOS and increase the risk of requiring postoperative blood transfusions. However, anemia should be regarded as a characteristic that can add to the outcome in a cumulative manner, as opposed to an isolated factor. Further research is needed on how to better manage preoperative anemia in order to improve patients' outcomes.

The Turtle Neck Sign: Identification of Severe Retracted Distal Biceps Tendon Rupture.

BACKGROUND: Chronic tendon retraction subsequent to distal biceps tendon rupture significantly increases repair difficulty and potential for tendon grafting. Biceps tendons that appear short or absent with magnetic resonance imaging (MRI) or that cannot be readily identified at surgery may erroneously be classified as irreparable. These apparent "absent" biceps tendons may actually be retracted and curled up inside the muscle, visually resembling the head-neck of a turtle retracted inside its shell (the "turtle neck sign"). When located, these tendons could be unfolded and repaired primarily. This type of tendon retraction seems to be associated with high-degree ruptures and larcertus fibrosus tears. PURPOSE: To test the hypothesis that tendon retractions with a turtle neck sign on MRI are more associated with high-degree ruptures and larcertus fibrosus tears versus tendon tears with simple linear retraction. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Retracted distal biceps tendon ruptures on sagittal MRI were categorized as linear retraction or curled-up (turtle neck) retraction. Retraction length, injury severity, and lacertus fibrosus tears were analyzed. RESULTS: The authors retrospectively analyzed the patient records of 85 consecutive traumatic distal biceps tendon ruptures from 2003 to 2019; the final study cohort was 37 patients. Injury-to-surgery timing was as follows: <3 weeks, 43% (16 cases); 3 weeks to 3 months, 32% (12 cases); and >3 months, 24% (9 cases). Overall, 19 patients had linear retraction <7 cm (mean, 3.3 ± 1.9 cm) and 18 patients had a turtle neck retraction ≥7 cm (mean, 9.1 ± 1.6 cm). The injury-to-surgery time (median [± interquartile range]) was 27 days (±90 days) in the linear retraction group and 23 days (±65 days) in the turtle neck retraction group. The turtle neck retraction group had a significantly higher occurrence of abnormal hook test findings, complete distal biceps tendon rupture, and lacertus fibrosus tears compared with the linear retraction group (100% vs 58%, 100% vs 68%, and 100% vs 37%, respectively; P ≤ .02). However, significant repairability differences were not found. CONCLUSION: Highly retracted distal biceps turtle neck sign tendon ruptures occur frequently in association with high-degree ruptures and lacertus fibrosus tears. The presence of a turtle neck retraction did not affect reparability. Surgeons should be aware of this curled-up retraction to avoid mistaking it for an absent tendon or a muscle-tendon disruption.

Differences in Cytotoxicity of Lidocaine, Ropivacaine, and Bupivacaine on the Viability and Metabolic Activity of Human Adipose-Derived Mesenchymal Stem Cells.

PURPOSE: We evaluated biological effects of distinct local anesthetics on human adipose-derived mesenchymal stem cells when applied to reduce periprocedural pain during mesenchymal stem cell injections. METHODS AND MATERIALS: Metabolic activity (MTS assay), viability (Live/Dead stain), and gene expression (quantitative real-time reverse-transcriptase polymerase chain reaction) were measured in mesenchymal stem cells incubated with various concentrations of lidocaine, ropivacaine, or bupivacaine during a 12-hr time course. RESULTS: Cell viability and metabolic activity decreased in a dose, time, and substance-specific manner after exposure to lidocaine, ropivacaine, and bupivacaine, with ropivacaine being the least cytotoxic. Cell viability decreases after brief exposure (<1.5 hrs) at clinically relevant concentrations (eg, 8 mg/ml of lidocaine, 2.5 mg/ml of ropivacaine or bupivacaine). Mesenchymal stem cells exposed to local anesthetics change their expression of mRNA biomarkers for stress response (EGR1, EGR2), proliferation (MKI67, HIST2H4A), ECM (COL1A1, COL3A1), and cell surface marker (CD105). CONCLUSIONS: Local anesthetics are cytotoxic to clinical-grade human mesenchymal stem cells in a dose-, time-, and agent-dependent manner and change expression of ECM, proliferation, and cell surface markers. Lidocaine and bupivacaine are more cytotoxic than ropivacaine. Single-dose injections of local anesthetics may affect the biological properties of mesenchymal stem cells in vitro but may not affect the effective dose of MSCs in a clinical setting.

Hypothermia and nutrient deprivation alter viability of human adipose-derived mesenchymal stem cells.

PURPOSE: Adipose-derived mesenchymal stem cells (MSCs) are attractive biological agents in regenerative medicine. To optimize cell therapies, it is necessary to determine the most effective delivery method for MSCs. Therefore, we evaluated the biological properties of MSCs after exposure to various temperatures to define optimal storage conditions prior to therapeutic delivery of MSCs. DESIGN: Prospective observational study. METHODS AND MATERIALS: Adherent and non-adherent MSCs were incubated at multiple temperatures (i.e., 4, 23 and 37 °C) in Lactated Ringers (LR) solution lacking essential cell growth ingredients, or in culture media which is optimized for cell growth. Cells were assessed either after the temperature changes (4 h) or after recovery (24 h). Metabolic activity of MSCs, cell number and expression of representative mRNA biomarkers were evaluated to assess the biological effects of temperature. We monitored changes in mRNAs expression related to cytoprotective- or stress-related responses (e.g., FOS, JUN, ATF1, ATF4, EGR1, EGR2, MYC), proliferation (e.g., HIST2H4, CCNB2), and extracellular matrix production (ECM; e.g., COL3A1, COL1A1) by quantitative real time reverse-transcriptase polymerase chain reaction (RT-qPCR) analysis. RESULTS: Our study demonstrates that storing MSCs in Lactated Ringers (LR) solution for 4 h decreases cell number and metabolic activity. The number of viable MSCs decreased significantly when cultured at physiological temperature (37 °C) and severe hypothermia (4 °C), while cells grown at ambient temperature (23 °C) exhibited the least detrimental effects. There were no appreciable biological differences in mRNA markers for proliferation or ECM deposition at any of the temperatures. However, biomarkers related to cytoprotective- or stress-responses were selectively elevated depending on temperature or media type (i.e., LR versus standard media). CONCLUSION: The biological impact of nutrient-free media and temperature changes after 4 h exposure persists after a 24 h recovery period. Hence, storage temperature and media conditions should be optimized to improve effective dosing of MSCs.

Effect of Lidocaine on Viability and Gene Expression of Human Adipose-derived Mesenchymal Stem Cells: An in vitro Study.

OBJECTIVE: To assess the biologic effects of lidocaine on the viability, proliferation, and function of human adipose tissue-derived mesenchymal stromal/stem cells (MSCs) in vitro. METHODS: Adipose-derived MSCs from three donors were exposed to lidocaine at various dilutions (2 mg/mL to 8 mg/mL) and exposure times (0.5 to 4 hours). Cell number and viability, mitochondrial activity, and real-time reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) were analyzed at 0 (immediate effects) or 24 and 48 hours (recovery effects) after treatment with lidocaine. RESULTS: Trypan blue staining showed that increasing concentrations of lidocaine decreased the number of observable viable cells. 3-[4,5,dimethylthiazol-2-yl]-5-[3-carboxymethoxy-phenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTS) assays revealed a concentration- and time- dependent decline of mitochondrial activity and proliferative ability. Gene expression analysis by RT-qPCR revealed that adipose-derived MSCs exposed to lidocaine express robust levels of stress response/cytoprotective genes. However, higher concentrations of lidocaine caused a significant downregulation of these genes. No significant differences were observed in expression of extracellular matrix (ECM) markers COL1A1 and DCN except for COL3A1 (P < .05). Levels of messenger RNA (mRNA) for proliferation markers (CCNB2, HIST2H4A, P < .001) and MKI67 (P < .001) increased at 24 and 48 hours. Expression levels of several transcription factors- including SP1, PRRX1, and ATF1-were modulated in the same manner. MSC surface markers CD44 and CD105 demonstrated decreased expression immediately after treatment, but at 24 and 48 hours postexposure, the MSC markers showed no significant difference among groups. CONCLUSION: Lidocaine is toxic to MSCs in a dose- and time- dependent manner. MSC exposure to high (4-8 mg/mL) concentrations of lidocaine for prolonged periods can affect their biologic functions. Although the exposure time in vivo is short, it is essential to choose safe concentrations when applying lidocaine along with MSCs to avoid compromising the viability and potency of the stem cell therapy.

Sonographically Guided Plantaris Tendon Release: A Cadaveric Validation Study.

BACKGROUND: The plantaris tendon (PT) has been implicated in the pathogenesis of symptoms in a subset of patients with Achilles region pain syndromes and traditionally has been managed via open surgical resection. Although the PT can be visualized on ultrasound, a minimally invasive technique for sonographically guided PT release has not been formally described. OBJECTIVE: To validate a technique to perform sonographically guided PT release in an unembalmed cadaveric model. DESIGN: Prospective, cadaveric laboratory investigation. SETTING: Procedural skills laboratory in a tertiary medical center. SUBJECTS: Twenty unembalmed cadaveric knee-ankle-foot specimens (10 right, 10 left) obtained from 16 donors (6 male, 10 female) ages 55-96 years (mean 82.6 years) with body mass indexes of 14.1-33.2 kg/m2 (mean 23.3 kg/m2 ). METHODS: After simulated local anesthesia and sonographically guided hydrodissection of the plantaris tendon-Achilles tendon interval, a single experienced operator performed sonographically guided PT release on each specimen using an in-plane, lateral-to-medial approach, a commercially available, disposable 3.0-mm hook knife, and either a 17-5 MHz or 15-7 MHz linear array transducer. Each specimen was subsequently dissected to assess for PT release and iatrogenic injury. MAIN OUTCOME: Status of the PT, Achilles tendon, and regional neurovascular structures as determined by dissection. RESULTS: All 20 PT releases were completed in a single attempt through a 3- to 5-mm incision. Dissection confirmed complete PT release in all specimens without damage to the adjacent Achilles tendon or regional neurovascular structures. CONCLUSION: Sonographically guided PT release is technically feasible and can be performed while avoiding injury to the Achilles tendon and regional neurovascular structures. Additional research is warranted to further define the role of sonographically guided PT release in patients with suspected PT-mediated Achilles region pain syndromes. LEVEL OF EVIDENCE: IV.

Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-Derived Mesenchymal Stem Cells.

BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections, and the effects of these agents on MSCs represents a gap in knowledge. OBJECTIVE: To investigate the biological effects of contrast media (CM) that are coinjected with MSCs. DESIGN: Prospective observational study. SETTING: Academic medical center. PARTICIPANTS: Patient-derived clinical-grade culture expanded MSCs. INTERVENTIONS: Iohexol (Omnipaque300) was reduced to 12.5%, 25%, 50%, and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours, and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate-buffered saline as a control group. MAIN OUTCOME MEASURES: We examined cytotoxicity of iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction of related genes were analyzed immediately after exposure (day 0) and after 2 days of exposure (day 2). RESULTS: Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief, 30-minute exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs. CONCLUSIONS: CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during MSC therapy for disk-degenerative diseases. LEVEL OF EVIDENCE: To be determined.

Accessory neuropathy after sternotomy: Clinico-anatomical correlation supporting an inflammatory cause.

Inflammatory etiologies are becoming increasingly recognized as explanations of some neuropathies, especially those occurring in the perioperative period. Although "brachial neuritis" is known to affect extraplexal nerves, accessory nerve palsy following median sternotomy has been attributed to stretch on the nerve. To better elucidate stretch as a potential cause, a cadaveric study was performed. Two patients who developed accessory nerve palsy following median sternotomy are presented to illustrate features consistent with the diagnosis of a perioperative inflammatory neuropathy. Five adult unembalmed cadavers underwent exposure of the bilateral accessory nerves in the posterior cervical triangle. A median sternotomy was performed and self-retaining retractors positioned. With the head in neutral, left rotation and right rotation, retractors were opened as during surgery while observing and recording any accessory nerve movements. The self-retaining sternal retractors were fully opened to a mean inter-blade distance of 13 cm. Regardless of head position, from the initial retractor click to maximal opening there was no gross movement of the accessory nerve on the left or right sides. Opening self-retaining sternal retractors does not appear to stretch the accessory nerve in the posterior cervical triangle. Based on our clinical experience and cadaveric results, we believe that inflammatory conditions, (i.e., idiopathic brachial plexitis) can involve the accessory nerve, and might be triggered by surgical procedures. Clin. Anat. 31:417-421, 2018. © 2017 Wiley Periodicals, Inc.

Cytotoxicity of Local Anesthetics in Mesenchymal Stem Cells.

Cell therapy based on the trophic, mitogenic, and immunomodulatory capacity of mesenchymal stem cells is a promising treatment modality for degenerative musculoskeletal conditions. Local anesthetics have been commonly used in interventional procedures for alleviating pain, but local anesthetics may have negative impact on MSC dosing because of cytotoxicity or other biological effects. Because previous studies have not reached consensus yet on the potential complications of local anesthetics in cell therapy, we reviewed 11 studies that involve in vitro experimentation with MSCs using aminoamide-type anesthetics including lidocaine, ropivacaine, mepivacaine, bupivacaine, articaine, and prilocaine. Three studies that compare the effects of different types of local anesthetic agents showed that ropivacaine has the least detrimental effects on mesenchymal stem cell populations, whereas lidocaine seems to have the most significant effects on stem cell viability. Concentration- and time-dependent effects on cell viability were reported with bupivacaine, ropivacaine, lidocaine, and mepivacaine. We conclude that local anesthetic agents have time- and concentration-dependent detrimental effects on MSCs. However, in vivo studies will be required to understand the interactions of these agents with MSCs, because in vitro studies cannot replicate the pharmacokinetics of anesthetics in vivo or the recovery of MSCs in a more physiological environment.

Ultrasound-guided hydrodissection decreases gliding resistance of the median nerve within the carpal tunnel.

INTRODUCTION: The aim of this study was to assess alterations in median nerve (MN) biomechanics within the carpal tunnel resulting from ultrasound-guided hydrodissection in a cadaveric model. METHODS: Twelve fresh frozen human cadaver hands were used. MN gliding resistance was measured at baseline and posthydrodissection, by pulling the nerve proximally and then returning it to the origin. Six specimens were treated with hydrodissection, and 6 were used as controls. RESULTS: In the hydrodissection group there was a significant reduction in mean peak gliding resistance of 92.9 ± 34.8 mN between baseline and immediately posthydrodissection (21.4% ± 10.5%; P = 0.001). No significant reduction between baseline and the second cycle occurred in the control group: 9.6 ± 29.8 mN (0.4% ± 5.3%; P = 0.467). DISCUSSION: Hydrodissection can decrease the gliding resistance of the MN within the carpal tunnel, at least in wrists unaffected by carpal tunnel syndrome. A clinical trial of hydrodissection seems justified. Muscle Nerve 57: 25-32, 2018.

Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial.

Adipose-derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra-articular joint space. Culture-expanded human AMSCs grown in human platelet-lysate were delivered via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x-ray, magnetic resonance imaging, and histopathology. Intra-articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra-articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910-922.

Ultrasound-Guided Fasciotomy for Chronic Exertional Compartment Syndrome: A Cadaveric Investigation.

BACKGROUND: Chronic exertional compartment syndrome (CECS) is a common cause of exertional leg pain. It is commonly treated with a surgical fasciotomy, which has a surgical complication rate of up to 16% and takes approximately 6-12 weeks to return to preprocedure activity levels. Therefore, the development of a less invasive, effective outpatient intervention to treat CECS is desirable. OBJECTIVE: To describe and validate an ultrasound-guided (USG) fasciotomy technique for the anterior and lateral compartments of the lower limb in an unembalmed cadaveric model. DESIGN: Prospective, cadaveric laboratory investigation. SETTING: Academic institution procedural skills laboratory. SUBJECTS: Ten unembalmed cadaveric knee-ankle-foot specimens from 1 female (2 specimens) and 7 male donors aged 62-91 years (mean 78.6 years) with body mass indices of 18.9-35.3 kg/m2 (mean 27.1 kg/m2). METHODS: Two experienced operators each performed USG anterior and lateral compartment fasciotomies on 5 unembalmed cadaveric legs. A third physician subsequently dissected the legs to assess the continuity of the fasciotomies and to identify any neurovascular damage related to the procedures. MAIN OUTCOME MEASURES: Fasciotomy length (in centimeters) and classification by completeness (achieved target length or did not achieve target length) and continuity (continuous or discontinuous) based on predetermined criteria. Muscles, retinaculae, and neurovascular structures were assessed for damage. RESULTS: No neurovascular injuries occurred in any of the 20 USG fasciotomies. The average fasciotomy length was 22.5 cm. All 20 of the fasciotomies achieved the target length. A continuous cephalocaudal fasciotomy was accomplished in 13 of 20 fasciotomies. When a fasciotomy was not continuous, the average length and number of intact fascial bands was 1.52 cm and 2.3, respectively. CONCLUSIONS: USG fasciotomy of the anterior and lateral leg compartments can be safely performed in a cadaveric model and can achieve a fasciotomy length comparable to surgical fasciotomy. Most procedures successfully achieved a continuous cephalocaudal fasciotomy, although small areas of intact fascial bands were identified in approximately one-third of procedures. The clinical significance of this finding is indeterminate. Given the safety demonstrated with this minimally invasive USG fasciotomy in a cadaveric model, further research is warranted to develop and refine the technique for clinical application. LEVEL OF EVIDENCE: Not applicable.

Sonographic Visualization of Thenar Motor Branch of the Median Nerve: A Cadaveric Validation Study.

BACKGROUND: The thenar motor branch (TMB) of the median nerve may be affected in carpal tunnel syndrome and can be injured during carpal tunnel surgery. Although ultrasound has been used to identify small nerves throughout the body, the sonographic evaluation of the TMB has not been investigated formally. OBJECTIVE: To document the ability of ultrasound to visualize the TMB of the median nerve in an unembalmed cadaveric model. DESIGN: Prospective laboratory investigation. SETTING: Procedural skills laboratory at a tertiary medical center. METHODS: On the basis of anatomical descriptions, dissection and clinical experience, a technique was developed to sonographically identify the presumed TMB of the median nerve at the distal carpal tunnel. A single, experienced examiner then identified the presumed TMB in 10 unembalmed, cadaveric upper limb specimens (4 right, 6 left) obtained from 9 donors (4 male, 5 female) ages 76-85 years with body mass indices of 18.2-29.5 kg/m2 with both 12-3 MHZ and 16-7 MHz linear array transducers. The same examiner then injected 0.2-0.3 mL of diluted colored latex into and around the presumed TMB using direct ultrasound guidance. At a minimum of 24 hours postinjection, specimens were dissected under loupe magnification to determine the location of the latex injectate. MAIN OUTCOME MEASURE: The location of latex injectate relative to the anatomically identified TMB. RESULTS: A vertical, linear, hypoechogenic region was sonographically identified arising from the median nerve at the distal carpal tunnel in all 10 specimens and was hypothesized to represent the vertical segment of the TMB. Both transducers allowed identification of the TMB, although localization was subjectively facilitated by the higher frequency transducer. All 10 sonographically guided injections placed latex into and around the TMB of the median nerve, confirming that ultrasound had accurately identified the TMB. CONCLUSIONS: Sonographic evaluation of the TMB of the median nerve is technically feasible and should be considered when clinically indicated. Further research and clinical experience is necessary to define the role of sonographic TMB imaging in the evaluation and management of patients with carpal tunnel syndrome. LEVEL OF EVIDENCE: IV.

Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production.

BACKGROUND: Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL). METHODS: In this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors. RESULTS: We characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells. CONCLUSIONS: Our study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria. CLINICAL TRIALS: Use of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC): Clinicaltrials.gov NCT01931007 . Registered August 26, 2013. MSC for Occlusive Disease of the Kidney: Clinicaltrials.gov NCT01840540 . Registered April 23, 2013. Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Clinicaltrials.gov NCT02315027 . Registered October 31, 2014. Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease. Clinicaltrials.gov NCT00366145 . Registered August 17, 2006. A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis. Clinicaltrials.gov NCT01609283 . Registered May 18, 2012.

Current Concepts and the Role of Surgery in the Treatment of Jumper's Knee.

Jumper's knee is a common cause of anterior knee pain among athletes and active populations. Numerous treatments have been described with variable results. To better delineate this, the authors reviewed all articles from 2000 to 2014 pertaining to the treatment of patellar tendinopathy, focusing namely on treatment of recalcitrant cases. Open and arthroscopic techniques were found to achieve similar satisfactory results in 81% (range, 45%-100%) and 91% (range, 86%-96%) of patients, respectively. Average time to return to play was 5.6 months and 5 months, respectively. A recently described technique, percutaneous ultrasonic tenotomy, potentially represents an attractive alternative option for definitive intervention. [Orthopedics. 2016; 39(6):e1028-e1035.].

Intra-articular bone marrow concentrate injection protocol: short-term efficacy in osteoarthritis.

AIM: Evaluate intra-articular injection of bone marrow concentrate (BMC), followed by platelet-rich plasma (PRP) injection at 8 weeks follow-up in moderate/severe osteoarthritis. DESIGN: Single center, retrospective Case Series (n = 125). METHODS: Bone marrow was aspirated/concentrated using a standardized technique. Patients received a single intra-articular injection of BMC, with follow-up injection of PRP at 8 weeks. RESULTS: Median absolute pain reduction in all joints was five points (71.4%) on visual analog scale. Median patient satisfaction was 9.0/10, while 91.7% indicated that they would repeat the procedure and 94% said that they would recommend the procedure to a friend. CONCLUSION: Intra-articular injection of BMC, followed by a PRP injection, can provide short-term benefits in moderate-to-severe osteoarthritis.

Ultrasound-Guided Interventional Procedures of the Wrist and Hand: Anatomy, Indications, and Techniques.

Acute and chronic wrist and hand conditions are commonly seen by neuromuscular and musculoskeletal specialists. High-frequency diagnostic ultrasonography (US) has facilitated advances in the diagnosis and interventional management of wrist and hand disorders. US provides excellent soft tissue resolution, accessibility, portability, lack of ionizing radiation, and the ability to dynamically assess disorders and precisely guide interventional procedures. This article review the relevant anatomy, indications, and interventional techniques for common disorders of the wrist and hand, including radiocarpal joint arthritis, scaphotrapeziotrapezoidal joint arthritis, trapeziometacarpal joint arthritis, phalangeal joint arthritis, first dorsal compartment tenosynovitis, ganglion cysts, and stenosing tenosynovitis.

Ultrasound-Guided Knee Procedures.

Most knee structures can be accurately targeted using ultrasound guidance. These structures are usually superficial, and the overlying soft tissues are mobile and compressible, facilitating excellent visualization with a high-frequency linear array transducer. The circumferential accessibility to the knee affords flexibility and often multiple procedural approach options. In most cases, an in-plane approach is easily achieved. Studies of ultrasonography-guided knee procedures have consistently shown high accuracy, and its use is particularly beneficial for obese patients, diagnostic injection specificity, safety, and precise targeting of pathology. More studies are needed to assess the clinical efficacy and cost-effectiveness of ultrasonography-guided knee procedures.