Intra-articular Route Research Articles

Efficacy of Peri-Operative Intra-Articular Compared with Intravenous Tranexamic Acid in Reducing Blood Loss after Primary Total Knee Arthroplasty

Abstract Background Total knee arthroplasty (TKA) is an established and reliable surgical procedure but it is associated with substantial perioperative blood loss. Tranexamic acid (TXA) reduces blood loss in this type of surgery. Aim of the Work The main primary outcome of this study is to investigate and compare the clinical effectiveness of intra-articular (IA) topical TXA with intravenous (IV) TXA in patients undergoing primary TKA regarding the efficacy in reducing blood loss. The other secondary targets for this study is to compare and discuss the efficacy of both regimens regarding the level of hemoglobin drop, reducing the need of blood transfusion, checking the safety of both interventions regarding the patient population and possible accompanying comorbidities, and the reduction of length of hospital stay and costs. Materials and Method The electronic search strategy included the following databases: PubMed, and Cochrane Library from January 2010 to January 2020. Published accessible completed studies on the use of tranexamic acid TXA via the intra-articular IA route or the intravenous IV route in patients undergoing primary total knee arthroplasty TKA were identified through searching PubMed, and Cochrane Library using this specific set of keywords: (((((total knee arthroplasty) AND (tranexamic acid)) AND (intravenous)) OR (intraarticular)) AND (primary)) AND (tourniquet). Results This meta-analysis demonstrates the statistically significant favoring of IA-TXA over IV-TXA in reducing blood loss and it demonstrates the statistically significant favoring of IV-TXA over IA-TXA in postoperative hemoglobin level drop. Conclusion Both IV-TXA and IA-TXA are equivalent effectively in reducing the need for postoperative blood transfusion and consequently helps reduce the possible accompanying complications of blood transfusion.

Local and Systemic Peptide Therapies for Soft Tissue Regeneration: A Narrative Review.

Background: The musculoskeletal system, due to inherent structure and function, lends itself to contributing toward joint pain, whether from inflammatory disorders such as rheumatoid arthritis, degenerative diseases such as osteoarthritis, or trauma causing soft tissue injury. Administration of peptides for treatment of joint pain or inflammation is an emerging line of therapy that seeks to offer therapeutic benefits while remaining safe and relatively non-invasive. Purpose: The purpose of this study is to review the current literature on existing oral peptide agents, intra-articular peptide agents, and new developments in human trials to assess route of administration (RoA) for drug delivery in terms of soft tissue regeneration. Study Design: Narrative Review. Methods: A comprehensive literature search was conducted using the PubMed database. The search included medical subject headings (MeSH) terms related to peptide therapy, soft tissue regeneration, and RoA. Inclusion criteria comprised articles focusing on the mechanisms of action of peptides, clinical or biochemical outcomes, and review articles. Exclusion criteria included insufficient literature or studies not meeting the set evidence level. Conclusion: The review identified various peptides demonstrating efficacy in soft tissue repair. Oral and intra-articular peptides showed distinct advantages in soft tissue regeneration, with intra-articular routes providing localized effects and oral routes offering systemic benefits. However, both routes have limitations in bioavailability and absorption. Still in their infancy, further inquiries/research into the properties and efficacy of emerging peptides will be necessary before widespread use. As a viable alternative prior to surgical intervention, peptide treatments present as promising candidates for positive outcomes in soft tissue regeneration.

Melatonin hyalurosomes in collagen thermosensitive gel as a potential repurposing approach for rheumatoid arthritis management via the intra-articular route

Despite the fact that several rheumatoid arthritis treatments have been utilized, none of them achieved complete joint healing and has been accompanied by several side effects that compromise patient compliance. This study aims to provide an effective safe RA treatment with minimum side effects through the encapsulation of melatonin (MEL) in hyalurosomes and loading these hyalurosomes in collagen thermos-sensitive poloxamer 407 (PCO) hydrogels, followed by their intra-articular administration in AIA model rats. In vitro characterization of MEL-hyalurosomes and PCO hydrogel along with in vivo evaluation of the selected formulation were conducted. Particle size, PDI and EE % of the selected formulation were 71.5 nm, 0.09 and 90 %. TEM micrographs demonstrated that the particles had spherical shape with no aggregation signs. Loading PCO hydrogels with MEL-hyalurosomes did not cause significant changes in pH although it increased its viscosity and injection time. FTIR analysis showed that no interactions were noted among the delivery system components. In vivo results revealed the superior effect of MEL-hyalurosomes PCO hydrogel over MEL-PCO hydrogel and blank PCO hydrogels in improving joint healing, cartilage repair, pannus formation and cell infiltrations. Also, MEL-hyalurosomes PCO hydrogel group showed comparable levels of TNF-α, IL1, MDA, NRF2 and HO-1 with the negative control group. These findings highlight the MEL encapsulation role in augmenting its pharmacological effects along with the synergistic effect of hyaluronic acid in hyalurosomes and collagen in PCO hydrogel in promoting joint healing.

Pharmacokinetics of amikacin after intravenous, intra-articular, and combined intravenous and intra-articular administration in healthy neonatal foals.

Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra-articular (IA) administration. Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens. Eight healthy neonatal foals. Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 μg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility. Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean μg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals. Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.

Syringeable hydrogel based β-cyclodextrin and mixed micelles for methotrexate delivery

Herein, mixed micelles laden hydrogel with syringeable feature were designed for intra-articular route of Methotrexate (MTX). The ternary system (FP–B58) based on mixed Pluronic F127/P123 system and Brij 58 was selected to fabricate the polymeric micelle. The solubility of MTX was remarkable improved in ternary micelles system than that of the binary micells system. The MTX in FP-B58 was 16.53 ± 0.87 mg/ml, while MTX in the mixed Pluronic micelles was 12.67 ± 1.27 mg/ml. The mixed micelles laden hydrogel were obtained by host-guest interaction with β-cyclodextrin (βCD). With the addition of 6 wt% βCD into FP-B58@MTX, the sol–gel transition behaviour following a temperature change was observed, confirming the syringeable feature. Due to the enhancement in the physical network by the supplement of βCD, the kinetic release of MTX transformed from non-Fickian (micelles system) to Fickian (hydrogel system). Following the effective controlled release, the cytotoxic of MTX in hydrogel was reduced, whereas the anti-inflammatory effects was similar to raw MTX at similar dose. In conclusion, MTX-loaded mixed micelles laden hydrogel are an attractive drug delivery strategy for effectively managing and treating rheumatoid arthritis.

From co-delivery to synergistic anti-inflammatory effect: Studies on chitosan-stabilized Janus emulsions having chloroquine phosphate and flavopiridol in Complete Freund's Adjuvant induced arthritis rat model

For the first time, the co-delivery of chloroquine phosphate and flavopiridol by intra-articular route was achieved to provide local joint targeting in Complete Freund's Adjuvant-induced arthritis rat model. The presence of paired-bean structure onto the dispersed oil droplets of o/w nanosized emulsions allows efficient entrapment of two drugs (85.86–96.22 %). The dual drug-loaded emulsions displayed a differential in vitro drug release behavior, near normal cell viability in MTT assay, better cell uptake (internalization) and better reducing effect of mean immunofluorescence intensity of inflammatory proteins such as NF-κB and iNOS at in vitro RAW264.7 macrophage cell line. The radiographical study, ELISA test, RT-PCR study and H & E staining also indicated a reduction in joint tissue swelling, IL-6 and TNF-α levels diminution, fold change diminution in the mRNA expressions for NF-κB, IL-1β, IL-6 and PGE2 and maintenance of near normal histology at bone cartilage interface respectively. The results of metabolomic pathway analysis performed by LC-MS/MS method using the rat blood (plasma) collected from disease control and dual drug-loaded emulsions treatment groups revealed a new follow-up study to understand not only the disease progression but also the formulation therapeutic efficacy assessment.

Comparative Effects of Intra-Articular versus Intravenous Mesenchymal Stromal Cells Therapy in a Rat Model of Osteoarthritis by Destabilization of Medial Meniscus.

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.

Comparative Study of Intra-articular Dexmedetomidine Versus Ketamine as an Adjuvant Analgesic after Arthroscopy

Abstract Background: The primary aim of this study was to evaluate the analgesic effect and safety of intra-articular Dexmedetomidine versus Ketamine in patients undergoing knee arthroscopic surgeries. Material and Methods: A total of 100 patients were allocated into two equal groups (n= 50 in each group) using random numbers, in an allocation ratio of 1:1. Syringes were labelled either D (dexmedetomidine) or K (ketamine) and study drugs were injected via intra-articular route after completion of knee arthroscopy. Analgesic effect of study drugs was compared using VAS score at 6 hrs, 12 hrs and 24 hrs. Safety of study drugs was compared using mean HR, mean BP and adverse events observed. Results: Lower VAS score, increased time for first rescue analgesic requirement and decreased need for postoperative analgesics were observed in the dexmedetomidine group as compared to ketamine group. Mean HR and Mean BP were lower in patients receiving dexmedetomine compared to those receiving ketamine. Hypotension was detected in 2 patients receiving dexmedetomedine while 1 patient on ketamine developed delirium. Conclusion: Intra-articular use of dexmedetomidine is superior to ketamine for post-operative analgesia without significant adverse effects. Key words: Knee arthroscopy, Intra-articular Dexmedetomidine, Intra-articular Ketamine

Emerging Advances in Nanocarriers Approaches in the Effective Therapy of Pain Related Disorders: Recent Evidence and Futuristic Needs.

Pain disorders are the primary cause of disability nowadays. These disorders, such as rheumatoid arthritis (RA) and osteoarthritis (OA), cause loss of function, joint pain and inflammation and deteriorate the quality of life. The treatment of these inflammatory diseases includes anti-inflammatory drugs administered via intra-articular, topical or oral routes, physical rehabilitation or surgery. Owing to the various side effects these drugs could offer, the novel approaches and nanomaterials have shown potential to manage inflammatory diseases, prolonged half-life of anti-inflammatory drugs, reduced systemic toxicity, provide specific targeting, and refined their bioavailability. This review discusses in brief about the pain pathophysiology and its types. The review summarizes the conventional therapies used to treat pain disorders and the need for novel strategies to overcome the adverse effects of conventional therapies. The review describes the recent advancements in nanotherapeutics for inflammatory diseases using several lipids, polymers and other materials and their excellent efficiency in improving the treatment over conventional therapies. The results of the nanotherapeutic studies inferred that the necessity to use nanocarriers is due to their controlled release, targeting drug delivery to inflamed tissues, low toxicity and biocompatibility. Therefore, it is possible to assert that nanotechnology will emerge as a great tool for advancing the treatment of pain disorders in the near future.

Challenges in tolerogenic dendritic cell therapy for autoimmune diseases: the route of administration.

Tolerogenic dendritic cells (tolDCs) are a promising strategy to treat autoimmune diseases since they have the potential to re-educate and modulate pathological immune responses in an antigen-specific manner and, therefore, have minimal adverse effects on the immune system compared to conventional immunosuppressive treatments. TolDC therapy has demonstrated safety and efficacy in different experimental models of autoimmune disease, such as multiple sclerosis (MS), type 1 diabetes (T1D), and rheumatoid arthritis (RA). Moreover, data from phase I clinical trials have shown that therapy with tolDCs is safe and well tolerated by MS, T1D, and RA patients. Nevertheless, various parameters need to be optimized to increase tolDC efficacy. In this regard, one important parameter to be determined is the most appropriate route of administration. Several delivery routes, such as intravenous, subcutaneous, intraperitoneal, intradermal, intranodal, and intraarticular routes, have been used in experimental models as well as in phase I clinical trials. This review summarizes data obtained from preclinical and clinical studies of tolDC therapy in the treatment of MS, T1D, and RA and their animal models, as well as data from the context of cancer immunotherapy using mature peptide-loaded DC, and data from in vivo cell tracking experiments, to define the most appropriate route of tolDC administration in relation to the most feasible, safest, and effective therapeutic use.

Injectable Drug Delivery Systems for Osteoarthritis and Rheumatoid Arthritis.

Joint diseases are one of the most common causes of morbidity and disability worldwide. The main diseases that affect joint cartilage are osteoarthritis and rheumatoid arthritis, which require chronic treatment focused on symptomatic relief. Conventional drugs administered through systemic or intra-articular routes have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. Therefore, there is an urgent need to develop improved strategies for drug delivery, in particular, the use of micro- and nanotechnology-based methods. Encapsulation of therapeutic agents in delivery systems reduces drug efflux from the joint and protects against rapid cellular and enzymatic clearance following intra-articular injection. Consequently, the use of drug delivery systems decreases side effects and increases therapeutic efficacy due to enhanced drug retention in the intra-articular space. Additionally, the frequency of intra-articular administration is reduced, as delivery systems enable sustained drug release. This review summarizes various advanced drug delivery systems, such as nano- and microcarriers, developed for articular cartilage diseases.

Comparison of Intraarticular Versus Combined Intravenous and Intraarticular Tranexamic Acid Administration in Patients Undergoing Primary Unilateral Total Knee Arthroplasty: A Randomized Controlled Trial in the Middle Eastern Patient Population.

This study aimed to determine whether combined intravenous (IV) and intraarticular (IA) tranexamic acid (TXA) reduces blood loss and the requirement of blood transfusion compared to IA use alone in the middle eastern patients undergoing primary cemented unilateral total knee arthroplasty (TKA). The present study is a double-blind randomized controlled trial (RTC) comparing the efficacy of IA alone to combined IA and IV routes of TXA administration in patients undergoing primary cemented TKA using a tourniquet performed by two senior surgeons. There were 21 patients in the IA alone and 29 in the combined group. The primary outcome measure was blood transfusion requirement, hemoglobin drop, and the total estimated blood loss on day three of postoperative period. The secondary outcomes were complications including thromboembolic events, wound complications, periprosthetic infection, patient-reported outcomes (PROs) of pain visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and EuroQol 5-dimension (EQ-5D) as well as the range of motion (ROM) at one-year follow-up. None of the patients in either of the comparison group required blood transfusion in the perioperative period. The drop in hemoglobin levels (2.1±1.0 vs. 2.2±1.1, P=0.84) and the total estimated blood loss (884±489 vs. 877±324, P=0.96) on the third postoperative day in the IA alone group showed no statistically significant difference compared to that in the combined group. Moreover, there were no complications noted in patients of either group. At one-year follow-up, there was no significant difference between the two comparison groups regarding the mean PROs of pain VAS, WOMAC, and EQ-5D, as well as ROM. According to the obtained results, this RCT in the middle eastern patient population found no additional benefit of TXA administration through combined IV and IA route over the IA alone in reducing the requirement of blood transfusion and the total blood loss. Further similar studies with larger sample sizes are needed to ascertain the ideal route of TXA administration in patients undergoing primary TKA.

Trends in Practice Among Shoulder Specialists in the Management of Frozen Shoulder: A Consensus Survey.

Background:The management of frozen shoulder (FS) differs depending on experience level and variation between scientific guidelines and actual practice.Purpose:To determine the current trends and practices in the management of FS among shoulder specialists and compare them with senior shoulder specialists.Study Design:Consensus statement.Methods:A team of 15 senior shoulder specialists (faculty group) prepared a questionnaire comprising 26 questions regarding the definition, terminology, clinical signs, investigations, management, and prognosis of FS. The questionnaire was mailed to all the registered shoulder specialists of Shoulder and Elbow Society, India (SESI) (specialist group; n = 230), as well as to the faculty group (n = 15). The responses of the 2 groups were compared, and levels of consensus were determined: strong (>75%), broad (60%-74.9%), inconclusive (40%-59.9%), or disagreement (<40%).Result:Overall, 142 of the 230 participants in the specialist group and all 15 participants in the faculty group responded to the survey. Both groups strongly agreed that plain radiographs are required to rule out a secondary cause of FS, routine magnetic resonance imaging is not indicated to confirm FS, nonsteroidal anti-inflammatory drugs should be administered at bedtime, steroid injection (triamcinolone or methylprednisolone) is the next best option if analgesics fail to provide pain relief, passive physical therapy should be avoided in the freezing phase, <10% of patients would require any surgical intervention, and patients with diabetes and thyroid dysfunction tend to fare poorly. There was broad agreement that routine thyroid dysfunction screening is unnecessary for women, a single 40-mg steroid injection via intra-articular route is preferred, and arthroscopic capsular release (ACR) results in a better outcome than manipulation under anesthesia (MUA). Agreement was inconclusive regarding the use of combined random blood sugar (RBS) and glycosylated hemoglobin versus lone RBS to screen for diabetes in patients with FS, preference of ACR versus MUA to treat resistant FS, and the timing of surgical intervention. There was disagreement over the most appropriate term for FS, the preferred physical therapy modality for pain relief, the most important movement restriction for early diagnosis of FS, and complications seen after MUA.Conclusion:This survey summarized the trend in prevalent practices regarding FS among the shoulder specialists and senior shoulder surgeons of SESI.

“A COMPARATIVE EVALUATION OF EFFECT OF INTRA ARTICULAR FENTANYL VERSUS DEXMEDETOMIDINE AS ADJUVANT TO ROPIVACAINE ON POST OPERATIVE PAIN IN KNEE ARTHROSCOPIC SURGERIES”

Background: Knee arthroscopy involves good repair of knee ligaments and menisci with minimal injuries but with variable degree of post operative pain. This pain can be minimal in some but can be very distressing in others. This study aims at evaluating effect of intra articular fentanyl versus dexmedetomidine as adjuvant to ropivacaine on post operative pain in knee arthroscopic surgeries. Ninety patients of ASA Class I Materials and Methods: /II, aged 20–60 years posted for arthroscopic knee surgery were randomly divided into Group R (control group),Group RF(fentanyl) and Group RD (dexmedetomidine) with 30 patients in each group. Anaesthetic technique used was spinal anaesthesia in all patients. Group I patients received Ropivacaine 0.75% 22 ml , group II received Ropivacaine 0.75% 20 ml +Fentanyl 1mcg/kg and Group III received 1 µg/kg dexmedetomidine diluted to 20 ml Ropivacaine 0.75% via intra-articular route at end of procedure. VAS score for 24 h, time to rst rescue analgesia and total dose of analgesic required in each group was evaluated. Results: VAS scores were signicantly lower in Group III, time to rst analgesic requirement was highest in group III (412.2±34.9mins) and lowest in group I (280.4±18.8mins), P value 0.002. Total dose of analgesic used in Group III (166.667±47.946 mg) patients was signicantly lesser compared to patients in Group I (273.33±44.978 mg) and group II (183.33±46.113 mg), P value 0.0226. Intra-articular dexmedetomidine as adjuvant t Conclusion: o 0.75% ropivacaine is effective in providing prolonged postoperative analgesia and decreases total analgesic requirements without any signicant side effects after arthroscopic knee procedures.

Exploration of novel drug delivery systems in topical management of osteoarthritis.

Osteoarthritis is one of the foremost disabling disorders in the world. There is no definitive treatment to prevent the progression of osteoarthritis. Hence, palliative treatment aims at minimizing pain, disability and improving function, performance and quality of life. Oral administration of nonsteroidal anti-inflammatory drug is associated with number of adverse effects and reduced therapeutic efficacy. Intra-articular injection has been the preferred route of drug administration. However, the clearance of drug from the arthritic site, risk of infections, cost and the pain associated with frequent injections make this route highly non-compliant to patients. Since osteoarthritis is a chronic condition which requires treatment for prolonged duration, there is an urgent need for another administration route which circumvents the hindrances linked with intra-articular route. Transdermal route across the skin locally at the osteoarthritis site could help in surpassing the disadvantages associated with intra-articular route. However, traversing skin barrier and reaching the chondrocytes with sufficient amount of the drug is extremely difficult. Nanocarrier-based approaches could hold an answer to the said shortcomings owing to their reduced size, targeting tunability and site specificity. In this article, we discuss the pathophysiology of osteoarthritis, molecular targets, and utilization of nanocarrier-based approaches to strategize the treatment of osteoarthritis in a new direction, i.e. topical delivery of nanocarriers in osteoarthritis.

Polymer nanotherapeutics: A versatile platform for effective rheumatoid arthritis therapy.

Rheumatoid arthritis is an aggressive and severely debilitating disorder that is characterized by joint pain and cartilage damage. It restricts mobility in patients, leaving them unable to carry out simple tasks. RA presents itself with severe lasting pain, swelling and stiffness in the joints and may cause permanent disability in patients. Treatment regimens currently employed for rheumatoid arthritis revolve around keeping clinical symptoms like joint pain, inflammation, swelling and stiffness at bay. The current therapeutic interventions in rheumatoid arthritis involve the use of non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying anti-rheumatic drugs and newer biological drugs that are engineered for inhibiting the expression of pro-inflammatory mediators. These conventional drugs are plagued with severe adverse effects because of their higher systemic distribution, lack of specificity and higher doses. Oral, intra-articular, and intravenous routes are routinely used for drug delivery which is associated with decreased patient compliance, high cost, poor bioavailability and rapid systemic clearance. All these drawbacks have enticed researchers to create novel strategies for drug delivery, the main approach being nanocarrier-based systems. In this article, we aim to consolidate the remarkable contributions of polymeric carrier systems including microneedle technology and smart trigger-responsive polymeric carriers in the management of rheumatoid arthritis along with its detailed pathophysiology. This review also briefly describes the safety and regulatory aspects of polymer therapeutics.

Effectiveness of Analgesics in the Treatment of Temporomandibular Dysfunction: A Systematic Literature Review

Introduction: Temporo-mandibular dysfunctions correspond to a defect adaptation of the manducatory apparatus. Different therapeutic methods are available for the treatment of these pathologies: Splints, physical therapies, occlusal therapies, surgery or pharmacological treatments. The objective of our work is to analyze the clinical effectiveness of analgesics in the treatment of disorders of the masticatory apparatus by applying the Evidence approach Based Dentistry. Methods: The collection of data from the literature scientific was carried out among the production that appeared during the period from 2011 to 2021. The documentary research was carried out using accessible databases via the Internet namely MEDLINE, ELSEVIER and Cochrane Database of Systematic through their PubMed, Science Direct and Cochrane library search engines, as well as the website Google Scholar. A bottom-up manual search covering the same study period was carried out in order to enrich our bibliography. The writing of this systematic review followed the guidelines of the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: 9 relevant randomized clinical trials were selected after critical reading guided by the CASP type reading grids. The items have been listed in 4 categories according to the route of administration of the analgesics (topical route, oral, intramuscular route and intra-articular route) and classified in tables according to the PICO criteria (Participants/Interventions/Comparison/Results “Outcomes”). The results of our study show a significant reduction in the intensity of the pain and the rates of cytokines as well as a significant increase in maximum mouth opening. Conclusion: The use of analgesics increases the efficacy of treatment by decreasing pain intensity and cytokine levels, through both their analgesic and anti-inflammatory actions. This efficacy is similar for both levels II and III. However, additional long-term clinical studies with a larger sample size are needed to confirm the data collected and to further explore the effect of analgesics in the treatment of TMDs.

Intra-articular versus intravenous administration of tranexamic acid in lower limb total arthroplasty: a systematic review and meta-analysis of randomised clinical trials.

The ideal route of tranexamic acid (TXA) administration in total hip arthroplasty (THA) or total knee arthroplasty (TKA) remains controversial. This study aims to identify the optima route of TXA administration in THA or TKA. PUBMED, EMBASE, MEDLINE and CENTRAL database were systematically searched until 4 August 2021 for randomised studies that compared intravenous (IV) or intra-articular (IA) administration of TXA in THA or TKA. Sixty-seven studies enrolling 8335 patients (IA: 4162; IV: 4173) were eligible for quantitative and qualitative analysis. Comparable results were demonstrated in the incidence of venous thromboembolisation (OR:0.96, p = 0.84), total blood loss (MD: -9.05, p = 0.36), drain output (MD: -7.36, p = 0.54), hidden blood loss (MD: -6.85, p = 0.47), postoperative haemoglobin level (MD: 0.01, p = 0.91), haemoglobin drop (MD: -0.10, p = 0.22), blood transfusion rate (OR: 0.99, p = 0.87), total adverse events (OR: 1.12, p = 0.28), postoperative range of motion (MD: 1.08, p = 0.36), postoperative VAS pain score (MD: 0.13, p = 0.24) and postoperative D-dimer level (MD: 0.61, p = 0.64). IV route of TXA administration was associated with significantly longer length of hospital stay compared to IA route of administration (MD: -0.22, p = 0.01). In this meta-analysis, both IV and IA route of TXA administration were equally effective in managing blood loss and postoperative outcomes in lower limb joints arthroplasty. Level 1. PROSPERO Registration CRD42021271355.

Cbl-b modulated TrkA ubiquitination and function in the dorsal root ganglion of mice

Casitas B-lineage lymphoma b (Cbl-b) is one of the E3 ubiquitin ligases that ubiquitinate Tropomyosin-related kinase A (TrkA), a key nerve growth factor receptor involved in the pathological pain. Here we found that Cbl-b was abundant in dorsal root ganglion (DRG) neurons of mice and co-localized with TrkA. Ubiquitination of TrkA by Cbl-b exerted a tonic negative control over the protein level of TrkA. Knockdown of Cbl-b caused TrkA accumulation in DRGs and evoked mechanical and heat hypersensitivity in intact mice. Our data showed that knee osteoarthritis induced by destabilization of the medial meniscus (DMM) led to the dissociation of Cbl-b with TrkA in DRG neurons, which impaired the ability of Cbl-b to ubiquitinate TrkA and served as an important mechanism to cause TrkA-dependent pain sensitization. Viral expression of constitutively active Cbl-b in DRGs of osteoarthritic mice effectively repressed TrkA protein level and more importantly, alleviated mechanical allodynia and heat hyperalgesia. Viral delivery of Cbl-b through intra-articular route generated a similar analgesic action. These data suggested that ubiquitination of TrkA by Cbl-b might represent an effective way to treat the osteoarthritic pain.

Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment.

Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.