Adipose-derived regenerative therapies for the treatment of knee osteoarthritis

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.

Recent Traumatic Dislocations of the Shoulder in Adults: Epidemiological, Therapeutic and Evolutionary Aspects

Introduction: Shoulder dislocations represent about 50% of all joint dislocations. The objective was to describe the epidemiological, therapeutic and evolutionary aspects of traumatic shoulder dislocations in Bouaké. Methods: This retrospective and descriptive study was conducted between January 2017 and December 2019. It concerned patients over 15 years of age with a recent traumatic shoulder dislocation treated and followed in the department. The variables studied were epidemiological, therapeutic and evolutionary. The severity of the trauma was assessed according to the Injury Severity Score (ISS). Functional outcome was assessed according to the Constant score. Results: There were 49 patients (49 dislocations) out of 22,569 patients. The prevalence was 0.2%. The mean age was 32 years (17 - 62). There were 38 men (77.5%). The sex ratio was 3.4. Students predominated (n = 10;20.4%). The etiology was dominated by road traffic accidents (n = 19;38.8%). Anterior dislocation was the most common (n = 45;92%). The ISS score was minor (n = 46;93.8%). The mean time to reduction was 7 hours (4 - 16). Orthopaedic reduction using the Kocher technique predominated (n = 44;89.8%). The mean duration of external rotation immobilisation of the shoulder was 23 days (16 - 45). Recurrence occurred in 8 patients (21.6%). The functional outcome at a mean Constant follow-up of 15 months (8 - 20) was satisfactory (n = 44;89.8%). Conclusion: Traumatic dislocation of the shoulder represented 0.2%. Treatment was mainly orthopaedic. Recurrence was rare.

Revisiting Pauwels' classification of femoral neck fractures

Pauwels’femoral neck fracture classification is based on the biomechanical principle that shear stress and varus force increase along more vertically oriented fractures,resulting in higher risk of fracture displacement and ultimately nonunion.This principle continues to guide construct selection for femoral neck fracture internal fixation and is the foundation for treating non-union with valgus osteotomy.However,with poor inter-and intra-rater reliability,dated treatment recommendations,and unreliable prognostic value,the Pauwels classification cannot be directly applied in its entirety to the management of femoral neck fractures in modern practice.

Collagen type Ⅱ suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1-SMAD1 interaction

Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage.Collagen type II(COL2A1)was previously considered to be only a structural component of the cartilage matrix,but recently,it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy.However,the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear.In our study,a Col2a1 p.Gly1170Ser mutant mouse model was constructed,and Col2a1 loss was demonstrated in homozygotes.Loss of Col2a1 was found to accelerate chondrocyte hypertrophy through the bone morphogenetic protein(BMP)-SMAD1 pathway.Upon interacting with COL2A1,integrinβ1(ITGB1),the major receptor for COL2A1,competed with BMP receptors for binding to SMAD1 and then inhibited SMAD1 activation and nuclear import.COL2A1 could also activate ITGB1-induced ERK1/2 phosphorylation and,through ERK1/2-SMAD1 interaction,it further repressed SMAD1 activation,thus inhibiting BMP-SMAD1-mediated chondrocyte hypertrophy.Moreover,COL2A1 expression was downregulated,while chondrocyte hypertrophic markers and BMP-SMAD1 signaling activity were upregulated in degenerative human articular cartilage.Our study reveals novel mechanisms for the inhibition of chondrocyte hypertrophy by COL2A1 and suggests that the degradation and decrease in COL2A1 might initiate and promote osteoarthritis progression.

Effect of lengthening along the anatomical axis of the femur and its clinical impact

AIM To review and study the effect of lengthening along the anatomical axis of long bones and its relation to the mechanical axis deviation.METHODS We try in this review to calculate and discuss the exact clinical impact of lengthening along the anatomical axis of the femur on affecting the limb alignment. Also we used a trigonometric formula to predict the change of the femoral distal anatomical mechanical angle(AMA) after lengthening along the anatomical axis. RESULTS Lengthening along the anatomical axis of the femur by 10% of its original length results in reduction in the distal femoral AMA by 0.57 degrees. There is no objective experimental scientific data to prove that the Mechanical axis is passing via the center of the hip to the center of the knee. There is wide variation in normal anatomical axis for different populations. In deformity correction, surgeons try to reproduce the normal usual bone shape to regain normal function, which is mainly anatomical axis. CONCLUSION Lengthening of the femur along its anatomical axis results in mild reduction of the distal femoral AMA. This may partially compensate for the expected mechanical axis lateralisation and hence justify its minimal clinical impact.

Study on roles of gap junctional intercellular communication in low dose parat hyroid hormones-induced bone anabolism in vitro

AIM:To investigate mediating and regulatory effects of osteoblastic gap juncti onal intercellular communication(GJIC) on low-dose parathyroid hormones(PTH)-s timulated bone formation activities in vitro.METHODS:Rat calvarial osteoblasts ( ROBs) in cultures were divided into three groups according to the different mode of exposure.Group A: vehicle (sodium acetate, SA)-treated group; Group B:1×10-8 mol/L hPTH(1-34) intermittent exposure group;Group C:1×10-8 mol/L hPTH(1-34) +1×10-7mol/L TPA exposure group.48 h incubation cycles in three groups were repeated for eight times.GJIC and mineralized bone nodules formation in thr ee groups were detected using Lucifer Yellow (LY) scrape loading dye transfer (S LDT) and mineralized nodule staining together with nodule index,respectively. RE SULTS:At various measuring time points of SA×6 h in group A,PTH×6 h in group B ,PTH×6 h+1 h in group B and PTH×6 h+TPA×1 h in group C,LY(+) cell numbers were 6.8±2.5,19.5±6.5,14.0±3.6 and 5.7±2.4,respectively.Diffusion and transf er of LY fluorescent probe was much more noticeably discerned in group B than in group A and C(P< 0.01).Mineralized bone nodule indices were 45.2±12.5, 88.0±1 5.3 and 38.5±17.9 in group A,B and C respectively.Bone formation activity was m uch better revealed in group B than in group A and C (P< 0.01),whereas no statis tically significant difference of bone formation activities were found in group A compared with group C(P=0.465).CONCLUSION:Mediations and regulations of the co ordinating signals in osteoblastic network via GJIC essentially contribute to PT H-stimulated bone anabolism.However,disruption of GJIC not only hinders osteobl astic intercellular coordination but also frustrates PTH-induced bone formation activities in vitro.Therefore,GJIC may evidently play important roles in regula tions on low-dose PTH-induced bone formation.

Tocilizumab Significantly Decreases Reactive Oxygen Species Level in Patients with Rheumatoid Arthritis

To determine the effect of tocilizumab (TCZ) on reactive oxygen species (ROS) in 11 patients with rheumatoid arthritis (RA), reactive oxygen metabolites (d-ROM) were measured using a Free Radical Elective Evaluator. The Disease Activity Score (DAS28) and matrix metalloproteinase-3 (MMP-3) level were also evaluated. d-ROM measured 392 ± 110 Carratelli units [U. CARR] on initiation of TCZ, and significantly decreased to 237 ± 82, 248 ± 88, and 226 ± 91 U.CARR after 3, 6, and 12 months, respectively

Treatment of hip joint dislocation combined with femoral head fracture

Objective To discuss the treatment of the hip joint dislocation combined with femoral head fracture and its clinical therapeutic effects.Methods From July 2001 to July 2008,19 patients with hip joint dislocation combined with femoral head fracture underwent conservative therapy or surgical treatment.Classification was based on Pipkin's criteria,type Ⅰ four,type Ⅱ six,type Ⅲ six,type Ⅳ three.Various procedures were taken according to the different types of the fracture,the time of the fracture,and the age of the patients.The clinical therapeutic effects were analyzed.Results In type Ⅰ,four were rated as excellent by Harris Hip Score's criteria.In type Ⅱ,two rated as excellent,three as good and one as fair.In type Ⅲ,three rated as good,two as fair and one as poor.In type Ⅳ,one rated as excellent,one as good and one as fair,overall rate of excellent and good was 73.7%.Conclusion The treatment of Pipkin fracture should be based on multiple factors such as the type of fracture,the time of fracture,the age of patients and so on.The prognosis is directly related with those factors and the way of the treatment.

Bilateral Spontaneous Achilles Tendon Rupture without Any Predisposing Factors

Besides spontaneous rupture of achilles tendon is a rare condition which is usually associated with corticosteroid or fluoroquinolon usage, spontaneous rupture of Achilles tendon without any risk factors is extremely rare. In this report we aimed to present clinical features of a case of bilateral spontaneous achilles tendon rupture and tried to investigate potential etiologic factors. A 54 year old man was admitted to our emergency department as complaining bilateral ankle pain at the retrocalcaneal region. He had no trauma, any comorbidities or any drug consumption history. Painful achilles tendon gaps proximal to his ankles had been palpated and bilateral Thompson’s test positivity had been noted (Figures 1 and 2). He was unable to rise upon his toes however he was able to walk. American Orthopedic Foot and Ankle Society Hindfoot Scoring was calculated as 78 points. The rupture had been verified with a magnetic resonance imaging and his laboratory findings were all within normal limits (Figures 3 and 4).The patient did not approve an operation so conservative treatment with dorsiflexion limiting brace was applied and strengthening and stretching exercises of gastrosoleus was suggested. Atraumatic and bilateral cases with achilles rupture should be well investigated whether any systemic factors are coexistent. Besides well known corticosteroids or fluoroquinolone exposure, endocrinologic and rheumatological diseases, hypercholesterolaemia should be evaluated in terms of predisposing causes. Patients who have to use corticosteroids or fluoroquinolone, should be informed about achilles tendon rupture and be suggested do regular physical exercises in order to reduce the rupture risk. Despite predisposing factors, sometimes nothing can be associated with achilles tendon rupture as in our case. Genetic predisposition or a degenerative process of a tendon due to age may be underlying cause like in rotator cuff tears.

Guidelines for navigation-assisted spine surgery

Spinal surgery is a technically demanding and challenging procedure because of the complicated anatomical structures of the spine and its proximity to several important tissues.Surgical landmarks and fluoroscopy have been used for pedicle screw insertion but are found to produce inaccuracies in placement.Improving the safety and accuracy of spinal surgery has increasingly become a clinical concern.Computerassisted navigation is an extension and application of precision medicine in orthopaedic surgery and has significantly improved the accuracy of spinal surgery.However,no clinical guidelines have been published for this relatively new and fast-growing technique,thus potentially limiting its adoption.In accordance with the consensus of consultant specialists,literature reviews,and our local experience,these guidelines include the basic concepts of the navigation system,workflow of navigation-assisted spinal surgery,some common pitfalls,and recommended solutions.This work helps to standardize navigation-assisted spinal surgery,improve its clinical efficiency and precision,and shorten the clinical learning curve.

Triple-functional bone adhesive with enhanced internal fixation,bacteriostasis and osteoinductive properties for open fracture repair

At present,effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures.However,external fixation can cause nail tract infections and is ineffective for fixing small fracture fragments.Moreover,closed reduction and internal fixation during the early stage of injury can lead to potential bone infection,conducive to bone nonunion and delayed healing.Herein,we designed a bone adhesive with anti-infection,osteogenic and bone adhesion fixation properties to promote reduction and fixation of open fractures and subsequent soft tissue repair.It was prepared by the reaction of gelatin(Gel)and oxidized starch(OS)with vancomycin(VAN)-loaded mesoporous bioactive glass nanoparticles(MBGNs)covalently cross-linked with Schiff bases.Characterization and adhesion experiments were conducted to validate the successful preparation of the Gel-OS/VAN@MBGNs(GOVM-gel)adhesive.Meanwhile,in vitro cell experiments demonstrated its good antibacterial effects with the ability to stimulate bone marrow mesenchymal stem cell(BMSCs)proliferation,upregulate the expression of alkaline phosphatase(ALP)and osteogenic proteins(RunX2 and OPN)and enhance the deposition of calcium nodules.Additionally,we established a rat skull fracture model and a subcutaneous infection model.The histological analysis showed that bone adhesive enhanced osteogenesis,and in vivo experiments demonstrated that the number of inflammatory cells and bacteria was significantly reduced.Overall,the adhesive could promote early reduction of fractures and antibacterial and osteogenic effects,providing the foothold for treatment of this patient population.

Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury

Over the years,electroconductive hydrogels(ECHs)have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury(PNI)with diabetes,given their favorable mechanical and electrical properties identical to endogenous nerve tissue.Nevertheless,PNI causes the loss of locomotor function and inflammatory pain,especially in diabetic patients.It has been established that bone marrow stem cells-derived exosomes(BMSCs-Exos)have analgesic,anti-inflammatory and tissue regeneration properties.Herein,we designed an ECH loaded with BMSCs-Exos(ECH-Exos)electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief.Given its potent adhesive and self-healing properties,this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure,avoiding the cumbersome implantation process.Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells.Meanwhile,Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway,thereby attenuating inflammatory pain in diabetic PNI.Additionally,ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo,consequently ameliorating muscle denervation atrophy and further promoting functional restoration.Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration,functional restoration and pain relief in patients with diabetic PNI.

Septic Arthritis and Multifocal Osteomyelitis Caused by Capnocytophaga Canimorsus: A Case Report

Microbiological diagnosis of chronic osteoarticular infections remains a major challenge,particularly when the clinical presentation is atypical and the pathogen is uncommon.In this unique case,Capnocytophaga canimorsus,a microorganism belonging to the oral microbiota of some domestic animals,caused septic arthritis and multifocal osteomyelitis in the long bone of a 43-year-old immunocompetent man.The patient was treated with two-stage surgery and local and systemic antibiotic therapy,and had a successful recovery.C.canimorsus should be considered as a possible etiological agent in patients with osteoarticular pathology and a history of exposure to domestic animals.

Should proximal ruptures of the anterior rectus femoris muscle be treated surgically?

Purpose:No therapeutic consensus has been established about proximal ruptures of the rectus femoris muscle.The objective of this literature review is to determine a therapeutic course of action.Methods:We conducted a literature review on the PubMed database using the following keywords(in French and English,respectively):"quadriceps/quadriceps","droit antérieur/rectus femoris","proximal/proximal","chirurgie/surgical","avulsion/avulsion".We collected 266 articles,36 of them were selected,which were related to our topic:proximal rupture of the anterior rectus femoris.Patients with a proximal rupture of the rectus femoris,minor or major patient of traumatic origin were included in this study.Patients injured at another lesion level,or non-traumatic lesions of the proximal rectus femoris(tendinitis without ruptures,tumor or others)were excluded.For each patient,the indications,the type of treatment and the functional result were analyzed,with the time to recovery and the level of recovery from sports and professional activities(same sport/profession or not,same level or not)as the main criterion of judgment.Fisher exact test was used for statistical comparison.Results:The aims of conservative treatment are to be pain free for the patient,to fight hematoma and to rehabilitate the injury as quickly as possible.The surgical techniques are varied,with most consisting of either a reinsertion of the musculo-tendon stump or a resection of the scar tissue with myo-tendinoaponeurotic suture in place.The functional results are good for the majority of the treatments proposed,but the conservative treatment has a shorter recovery time(3 months vs.4 months for the best surgical results).Highly displaced bone avulsion is the only indication for first-line surgical treatment.Conslusion:The main disadvantage of conservative treatment is the risk of residual pain beyond 3 months(10%),justifying an MRI to guide secondary surgical treatment.We propose a treatment plan for proximal rupture of the proximal rectus femoris rupture.