Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis

BACKGROUND No effective treatment guarantees full recovery from osteoarthritis(OA),and few therapies have disadvantages.AIM To determine if bone marrow mesenchymal stem cells(BMMSCs)and hyaluronic acid(HA)treat ankle OA in Wistar rats.METHODS BMMSCs were characterized using flow cytometry with detection of surface markers[cluster of differentiation 90(CD90),CD105,CD34,and CD45].Fifty male Wistar rats were divided into five groups of 10 rats each:Group I,saline into the right tibiotarsal joint for 2 days;Group II,monosodium iodate(MIA)into the same joint;Groups III,MIA+BMMSCs;Group IV,MIA+HA;and Group V,MIA+BMMSCs+HA.BMMSCs(1×106 cells/rat),HA(75μg/rat),and BMMSCs(1×106 cells/rat)alongside HA(75μg/rat)were injected intra-articularly into the tibiotarsal joint of the right hind leg at the end of weeks 2,3,and 4 after the MIA injection.RESULTS The elevated right hind leg circumference values in the paw and arthritis clinical score of osteoarthritic rats were significantly ameliorated at weeks 4,5,and 6.Lipid peroxide significantly increased in the serum of osteoarthritic rats,whereas reduced serum glutathione and glutathione transferase levels were decreased.BMMSCs and HA significantly improved OA.The significantly elevated ankle matrix metalloproteinase 13(MMP-13)mRNA and transforming growth factor beta 1(TGF-β1)protein expression,and tumor necrosis factor alpha(TNF-α)and interleukin-17(IL-17)serum levels in osteoarthritic rats were significantly downregulated by BMMSCs and HA.The effects of BMMSCs and HA on serum TNF-αand IL-17 were more potent than their combination.The lowered serum IL-4 levels in osteoarthritic rats were significantly upregulated by BMMSCs and HA.Additionally,BMMSCs and HA caused a steady decrease in joint injury and cartilage degradation.CONCLUSION BMMSCs and/or HA have anti-arthritic effects mediated by antioxidant and anti-inflammatory effects on MIAinduced OA.MMP-13 and TGF-β1 expression improves BMMSCs and/or HA effects on OA in Wistar rats.

Clinical value of ankle flexion and extension exercises combined with a psychological intervention in knee osteoarthritis

BACKGROUND Considering the limited effectiveness of clinical interventions for knee osteoarthritis(KOA),it is necessary to continue to explore appropriate and effective treatment strategies to improve the condition of KOA patients.AIM To clarify the influence of ankle flexion and extension exercises combined with a psychological intervention on the psychological status and activities of daily living(ADLs)of patients with KOA.METHODS The research participants were 116 KOA patients admitted to The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine between May 2019 and May 2022,including 54 patients receiving routine treatment,care and psychological intervention(control group)and 62 patients additionally treated with ankle flexion and extension exercises(research group).The two groups were comparatively analyzed in terms of psychological status(Self-rating Anxiety/Depression Scale,SDS/SAS),ADLs,knee joint function(Lysholm Knee Scoring Scale),pain(Visual Analog Scale,VAS),fatigue(Multidimensional Fatigue Inventory,MFI),and quality of life(QoL;Short-Form 36 Item Health Survey,SF-36).RESULTS After evaluation,it was found that the postinterventional SDS,SAS,VAS,and MFI scores in the research group were significantly reduced compared with the baseline(before the intervention)values and those of the control group,while the postinterventional Lysholm,ADL and SF-36 scores were markedly elevated.CONCLUSION Therefore,ankle flexion and extension exercises are highly effective in easing negative psychological status,enhancing ADLs,daily living ability,knee joint function and QoL,and relieving pain and fatigue in KOA patients,thus warranting clinical promotion.

Distraction arthroplasty in osteoarthritis of the foot and ankle

Post-traumatic osteoarthritis(PTOA)is a complex and painful problem in the foot and ankle.Ninety percent of osteoarthritis cases in the foot and ankle can be classified as post-traumatic.PTOA can affect any of the 33 joints in the foot and the ankle.Distraction arthroplasty is a method for treatment of early arthritic joints without fusing or replacing them and its effectiveness has been well documented.The purpose of this case series is to present our successful experiences and positive results using distraction arthroplasty to treat PTOA in the ankle,subtalar,first metatarsophalangeal,and second tarsometatarsal joints,and to present distraction arthroplasty as a viable alternative to invasive joint sacrificing procedures such as arthrodesis or arthroplasty.Distraction Arthroplasty effectively and safely treats PTOA and improves the stability of joints in the Foot and Ankle.Additionally,the use of bone marrow aspirate concentrate as an adjuvant can improve the long-term functional and structural outcomes of the joint,and can prolong the need for further,more aggressive surgical interventions such as fusion or arthroplasty.

Chronic Ankle Instability: Therapeutic Exercise and Data Analysis

Background and Objectives: Ankle injuries are the most common type of injury in healthy active individuals. If not treated properly, recurrent sprains can lead to a condition of chronic ankle instability (CAI). The present paper examines some subjects with a previous history of acute inversion ankle sprain who have developed a subsequent condition of instability, grouping them according to inclusion criteria and analyzing them through four field tests considered objective by the scientific literature: SEBT test, BEES test, TIBT test, SHT test. The data obtained were stored in order to compare them following a re-education protocol aimed at improving proprioception, balance, walking and strengthening the extrinsic and intrinsic muscles of the foot. per year. The subjects were then divided into two categories: subjects with CAI > 1 year and subjects with CAI ≤ 1 year. A protocol lasting 6 weeks was administered to both groups, trying to work on improving balance in single stance, improving static and dynamic stability, strengthening the gluteus medius and maximus (pelvis stabilizers) and strengthening of the intrinsic muscles of the foot. At the end of the protocol the subjects were all re-evaluated with the same field tests used previously and the data obtained were compared both with the pre-protocol data and with the data measured by the control subjects.

Functional assessment and influencing factors after staged functional training in patients with ankle fractures

BACKGROUND The recovery of limb function after ankle fracture surgery is a gradual process.The main purpose of implementing early functional exercise,joint mobility,muscle contraction function,passive ankle flexion and extension exercises,or physical factor therapy techniques is to achieve the rapid recovery of normal physiological limb function.However,currently the most effective rehabilitation training method is staged limb functional exercise,which promotes rapid recovery of limb function while preventing adverse consequences caused by overwork or insufficient training.Staged limb functional exercise divides the rehabilitation process into multiple stages,each of which has specific training objectives and contents.This method helps patients gradually restore limb function.Nevertheless,some patients still exhibit poor limb function after standardized exercise.Therefore,a functional evaluation should be performed to analyze the impact of staged functional training after ankle fracture surgery.AIM To perform a functional evaluation and determine the influencing factors of staged functional training in patients with ankle fracture.METHODS A retrospective study enrolled 150 patients who underwent surgical treatment for ankle fracture from May 2020 to May 2022 at our hospital.Univariate and multivariate linear regression analyses were performed on general data,functional exercise compliance scale for orthopedic patients,Social Support Rating Scale(SSRS),American Orthopedic Foot and Ankle Score(AOFAS)Ankle-Hindfoot Score,and pain factors[serum bradykinin(BK),prostaglandin E2(PGE2),5-hydroxytryptamine(5-HT)].RESULTS Based on the AOFAS Ankle-Hindfoot Scale,the cases were divided into the excellent function(n=111)and ordinary function(n=39)groups.Univariate analysis revealed that monthly family income,education level,diabetes mellitus,functional exercise compliance scale of orthopedic patients score,SSRS,BK,PGE2,and 5-HT significantly influenced limb function after ankle fracture(P<0.05);Multiple linear regression analysis showed that the functional exercise compliance scale score,SSRS,BK,PGE2,and 5-HT were independent risk factors affecting functional performance after staged functional exercise(P<0.05).CONCLUSION Exercise compliance,SSRS,and pain level are the independent risk factors affecting functional performance after staged functional training following ankle surgery.Clinical nursing care after ankle surgery should include analgesic and health education measures to ensure optimal recovery of limb function.

Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a

BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examination results showed that the blank control group had the fastest progression of arthritis,the normal extracellular vesicle group had a relatively slower progression,and the engineered extracellular vesicle group had the slowest progression.Gross histological observation results showed that the blank control group had the most obvious signs of arthritis,the normal extracellular vesicle group showed signs of arthritis,and the engineered extracellular vesicle group showed no significant signs of arthritis.Using the Pelletier gross score evaluation,the engineered extracellular vesicle group had the slowest progression of arthritis.Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group,and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition.Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group.Compared to the normal extracellular vesicle group,the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells.CONCLUSION Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability,thereby protecting articular cartilage,and slowing the progression of KOA.

Unicompartmental knee arthroplasty vs high tibial osteotomy for knee osteoarthritis:A comparison of clinical and radiological outcomes

BACKGROUND Unicompartmental knee arthroplasty(UKA)and high tibial osteotomy(HTO)are well-established operative interventions in the treatment of knee osteoarthritis.However,which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate.Simultaneously,there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes,preoperatively and following HTO or UKA.AIM To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis:Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.METHODS This longitudinal observational study assessed a total of 42 patients that had undergone UKA(n=23)and HTO(n=19)to treat medial compartment knee osteoarthritis.Patient-reported outcome measures(PROMs)were collected to evaluate clinical outcome.These included two disease-specific(Knee Injury and Osteoarthritis Outcome Score,Oxford Knee Score)and two generic(EQ-5D-5L,Short Form-12)PROMs.The radiographic parameters of knee alignment assessed were the:Hip-knee-ankle angle,mechanical axis deviation and angle of Mikulicz line.RESULTS Statistical analyses demonstrated significant(P<0.001),preoperative to postoperative,improvements in the PROM scores of both groups.There were,however,no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group.Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively(P<0.05).Postoperatively,two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters(hip-knee-ankle angle,mechanical axis deviation)within the HTO group;yet no such associations were observed within the UKA group.CONCLUSION UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis.Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively;however,a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.

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.

Prevalence,Characteristics and Treatment of Knee Osteoarthritis in Urban Residents of Beijing,China:A Community-Based Cross-Sectional Study

Knee osteoarthritis(KOA)is a common progressive joint disease with chronic pain and movement disorders as the main clinical features.It is a major public health problem worldwide and it imposes serious medical and economic burdens.KOA accounts for nearly four-fifths of the global Osteoarthritis burden and increases with rising obesity and age[1].There are many reasons for the change in disease prevalence and risk factors,such as urbanization,lifestyle changes,population aging,and sex imbalances.

Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3

Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules downstream.This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)substrates.It demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology.We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in mice.Contrarily,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice.The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte health.These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

Analysis of a passive ankle exoskeleton for reduction of metabolic costs during walking

Modern conflicts demand substantial physical and psychological exertion,often resulting in fatigue and diminished combat or operational readiness.Several exoskeletons have been developed recently to address these challenges,presenting various limitations that affect their operational or everyday usability.This article evaluates the performance of a dual-purpose passive ankle exoskeleton developed for the reduction of metabolic costs during walking,seeking to identify a force element that could be applied to the target population.Based on the 6-min walk test,twenty-nine subjects participated in the study using three different force elements.The results indicate that it is possible to reduce metabolic expenditure while using the developed exoskeleton.Additionally,the comfort and range of motion results verify the exoskeleton's suitability for use in uneven terrain and during extended periods.Nevertheless,the choice of the force element should be tailored to each user,and the control system should be adjustable to optimise the exoskeleton's performance.

Configuration and Kinematics of a 3-DOF Generalized Spherical Parallel Mechanism for Ankle Rehabilitation

The kinematic equivalent model of an existing ankle-rehabilitation robot is inconsistent with the anatomical structure of the human ankle,which influences the rehabilitation effect.Therefore,this study equates the human ankle to the UR model and proposes a novel three degrees of freedom(3-DOF)generalized spherical parallel mechanism for ankle rehabilitation.The parallel mechanism has two spherical centers corresponding to the rotation centers of tibiotalar and subtalar joints.Using screw theory,the mobility of the parallel mechanism,which meets the requirements of the human ankle,is analyzed.The inverse kinematics are presented,and singularities are identified based on the Jacobian matrix.The workspaces of the parallel mechanism are obtained through the search method and compared with the motion range of the human ankle,which shows that the parallel mechanism can meet the motion demand of ankle rehabilitation.Additionally,based on the motion-force transmissibility,the performance atlases are plotted in the parameter optimal design space,and the optimum parameter is obtained according to the demands of practical applications.The results show that the parallel mechanism can meet the motion requirements of ankle rehabilitation and has excellent kinematic performance in its rehabilitation range,which provides a theoretical basis for the prototype design and experimental verification.

Type Synthesis of Self-Alignment Parallel Ankle Rehabilitation Robot with Suitable Passive Degrees of Freedom

The current parallel ankle rehabilitation robot(ARR)suffers from the problem of difficult real-time alignment of the human-robot joint center of rotation,which may lead to secondary injuries to the patient.This study investigates type synthesis of a parallel self-alignment ankle rehabilitation robot(PSAARR)based on the kinematic characteristics of ankle joint rotation center drift from the perspective of introducing"suitable passive degrees of freedom(DOF)"with a suitable number and form.First,the self-alignment principle of parallel ARR was proposed by deriving conditions for transforming a human-robot closed chain(HRCC)formed by an ARR and human body into a kinematic suitable constrained system and introducing conditions of"decoupled"and"less limb".Second,the relationship between the self-alignment principle and actuation wrenches(twists)of PSAARR was analyzed with the velocity Jacobian matrix as a"bridge".Subsequently,the type synthesis conditions of PSAARR were proposed.Third,a PSAARR synthesis method was proposed based on the screw theory and type of PSAARR synthesis conducted.Finally,an HRCC kinematic model was established to verify the self-alignment capability of the PSAARR.In this study,93 types of PSAARR limb structures were synthesized and the self-alignment capability of a human-robot joint axis was verified through kinematic analysis,which provides a theoretical basis for the design of such an ARR.

Foot and ankle surgery:Tourniquet placement site to cause as little postoperative pain as possible

There is controversy in the literature on where to place the tourniquet(thigh,calf,ankle)for foot and ankle surgery.While some authors prefer the ankle tourniquet to the calf tourniquet,others state that the surgeon can decide between using the thigh tourniquet or the ankle tourniquet,since there was no difference in postoperative pain between them.Where to place the tourniquet during foot and ankle surgery to cause the least possible postoperative pain to the patient as a result of the tourniquet is a common question in clinical practice.The reality is that,unfortunately,there is no consensus on this issue.Perhaps the only possible way to answer this question would be to conduct a comparative study with sufficient statistical power to reach scientifically sound conclusions.It does not seem easy to carry out such a study,but it would be important to be able to answer the question posed in the title of this Editorial once and for all.

Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis

Osteoarthritis(OA)is a major clinical challenge,and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets.Effective early treatments are urgently needed to prevent OA progression.The excessive amount of transforming growth factorβ(TGFβ)is one of the major causes of synovial fibrosis and subchondral bone sclerosis,and such pathogenic changes in early OA precede cartilage damage.Herein we report a novel strategy of intra-articular sustained-release of pirfenidone(PFD),a clinically-approved TGFβinhibitor,to achieve disease-modifying effects on early OA joints.We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1(as those levels found in patients’synovial fluid).A monthly injection strategy was then designed of using poly lactic-co-glycolic acid(PLGA)microparticles and hyaluronic acid(HA)solution to enable a sustained release of PFD(the“PLGA-PFD+HA”strategy).This strategy effectively regulated OA progression in destabilization of the medial meniscus(DMM)-induced OA mice model,including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA,and reduced synovitis and pain with cartilage preservation effects.This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

Knee Osteoarthritis Progression after Distal Femur Closing Wedge Osteotomy

Background: Despite the conservative treatment of tibio-femoral osteoarthritis through realignment osteotomies, the rate of total knee replacements following an osteotomy is increasing. The aim of this study was to identify the factors associated with the progression of knee osteoarthritis after a medial closing-wedge distal femoral osteotomy. Methods: Hospital-based observational study on 20 patients who underwent a medial closing-wedge distal femoral osteotomy evaluating the progression of osteoarthritis using the Kellgren and Laurence classification. The Wilcoxon test was used to compare the variation in the progressive stage of the Kellgren and Laurence classification of knee osteoarthritis preoperatively and at the final follow up. Univariate analysis made it possible to determine the factors associated with progression. The final significance threshold for statistical tests was set at 5% (p Results: Overall, the mean follow-up of 46 months ± 6.6 months, with a mean age of 43 years (range: 27 - 69 years) and a female predominance (M: F = 3/7). The progression of tibiofemoral osteoarthritis following a medial closing-wedge distal femoral osteotomy is associated with valgus or varum malalignment been a moderate valgus (OR 6.2 [1.5 - 42.7] at 95% CI;p-value = 0.02), a correction of the mechanical deviation angle with a valgus alignment (OR 2.7 [0.9 - 8.3] at 95% CI), and loss of correction (OR 3.8 [1.3 - 11.6] at 95% CI;p -value) for the lateral compartment while varus alignment (OR 1.7 [0.9 - 8.3] 95% CI, p-value = 0.05) and with rupture of the lateral cortex (OR 2.8 [1.7 - 11.5] 95% CI, p-value = 0.02) were those of the medial compartment. Conclusion: Distal femur closing wedge osteotomy does not definitively interrupt the progression of valgus knee osteoarthritis. The factors associated with the progression of this pathology are modifiable. Taking them into account when performing this surgical technique could improve the osteotomy survival curve.

Epidemiological, Clinical and Paraclinical Profile of Osteoarthritis of the Lower Limbs in Obese Patients at the Cocody University Teaching Hospital

Objective: To describe the epidemiological, clinical and paraclinical characteristics of osteoarthritis of the lower limbs in obese patients at the Cocody University Teaching Hospital. Methodology: This was an analytical cross-sectional study carried out in the rheumatology department of the Cocody UTH in Abidjan (Ivory Coast) from March 1 to April 30 2023. Patients who came for rheumatology consultation presenting with mechanical arthralgia of the lower limbs, who were obese, had radiographic images were included. All patients without radiographic images were excluded. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m. The Chi2 test was used to compare proportions and determine the existence of associations between osteoarthristis and obesity, obesity severity and radiographic stage of osteoarthritis as well as the functional impact. A p-value below a predefined threshold (p = 0,05) indicates a significant relationship between the variables. Result: Out of 185 patients received for osteoarthritis of the lower limbs during the study period, 136 were obese (74%). There were 115 women (84.6%) with an average age of 56.03 with a standard deviation of 12.72 years (extremes: 22 and 84 years). The main socio-professional category was the informal sector (30%). The majority of patients had a low socio-economic level (80.2%) and lived in urban areas (92.6%). The most common past medical history was hypertension (33.08%) followed by peptic ulcer disease (16.91%). Patients had a body mass index class 1 (81.6%), class 2 (15.40%) and class 3 (2.90%). The average duration of symptom progression until diagnosis was 11 months. Genu varum was the main static disorder (56.10%) and the knee joint was the dominant topography (90.4%) with a bilateral localization (80%). The average Lequesne index was greater than 8 (59.5%). The Kellgren and Lawrence radiographic stages were stage 1 (9.20%), stage 2 (46.90%), stage 3 (29.20%) and stage 4 (6.90%). The Obesity severity was significantly associated with osteoarthritis of the knee (p = 0.042). There was no statistically significant association between obesity severity and radiographic stage of osteoarthritis (p = 0.163) or functional impact (p = 0.180). Conclusion: Osteoarthritis of the lower limbs affected obese women and was dominated by stage 2 osteoarthritis of the knee (Kellgren and Lawrence). There is an association between the severity of obesity and osteoarthritis of the knee.