Current understanding of MSC-derived exosomes in the management of knee osteoarthritis.

Mesenchymal stem cell-derived exosomes (MSC-Exos) have been utilized as medicinal agents or as delivery vehicles in cartilage injuries and cartilage-based diseases. Given the ongoing emergence of evidence on the effector mechanisms and methods of the utility of the MSC-Exos in knee osteoarthritis, a comprehensive review of the current evidence is the need of the hour. Hence, in this article, we review the current understanding of the role of MSC-Exos in the management of knee osteoarthritis in view of their classification, characterization, biogenesis, mechanism of action, pathways involved in their therapeutic action, in-vitro evidence on cartilage regeneration, in-vivo evidence in OA knee models and recent advances in using MSC-Exos to better streamline future research from bench to bedside for OA knee.

Clinical effectiveness of reduction and fusion versus in situ fusion in the management of degenerative lumbar spondylolisthesis: a systematic review and meta-analysis.

PURPOSE: To compare the clinical effectiveness of reduction and fusion with in situ fusion in the management of patients with degenerative lumbar spondylolisthesis (DLS). METHODS: The systematic review was conducted following the PRISMA guidelines. Relevant studies were identified from PubMed, Embase, Scopus, Cochrane Library, ClinicalTrials.gov, and Google Scholar. The inclusion criteria were: (1) comparative studies of reduction and fusion versus in situ fusion for DLS patients, (2) outcomes reported as VAS/NRS, ODI, JOA score, operating time, blood loss, complication rate, fusion rate, or reoperation rate, (3) randomized controlled trials and observational studies published in English from the inception of the databases to January 2023. The exclusion criteria included: (1) reviews, case series, case reports, letters, and conference reports, (2) in vitro biomechanical studies and computational modeling studies, (3) no report on study outcomes. The risk of bias 2 (RoB2) tool and the Newcastle-Ottawa scale was conducted to assess the risk of bias of RCTs and observational studies, respectively. RESULTS: Five studies with a total of 704 patients were included (375 reduction and fusion, 329 in situ fusion). Operating time was significantly longer in the reduction and fusion group compared to in situ fusion group (weighted mean difference 7.20; 95% confidence interval 0.19, 14.21; P = 0.04). No additional significant intergroup differences were noted in terms of other outcomes analyzed. CONCLUSION: While the reduction and fusion group demonstrated a statistically longer operating time compared to the in situ fusion group, the clinical significance of this difference was minimal. The findings suggest no substantial superiority of lumbar fusion with reduction over without reduction for the management of DLS.

The efficiency of machine learning-assisted platform for article screening in systematic reviews in orthopaedics.

PURPOSE: With the development of machine learning and artificial intelligence, various platforms were developed to aid in the time-consuming process of article screening in systematic reviews. We aim to analyze the efficiency of a machine learning-assisted platform as an end-user to aid in the screening of the articles for selection into systematic review in orthopaedic surgery. METHODS: We included three previously published systematic reviews in the field of orthopaedics of increasing levels of difficulty in the structure of the research question to assess the efficiency of a platform with active-learning technology for article screening. We compared the efficiency of the platform compared to the traditional screening and also across the various scenarios tested. We performed five iterations for each review analyzed. The outcome parameters analyzed were the work saved at 95% recall (WSS-95), work saved at 100% recall (WSS-100), and relevant records found after screening the first 30% of the total records (RRF-30). RESULTS: The machine learning-assisted screening significantly improved the rate of identifying the relevant records compared to the traditional screening method (p<0.001). The WSS-95 for the easy, intermediate, and advanced screening scenarios were 78%, 59%, and 38%, respectively. The WSS-100 for the easy, intermediate, and advanced screening scenarios were 75%, 48%, and 7%, respectively. The RRF-30 for the easy, intermediate, and advanced screening scenarios were 97%, 86%, and 64%, respectively. We noted a significant reduction (p<0.001) in the efficiency with the increasing level of difficulty of the screening scenarios. CONCLUSION: The machine learning platform is significantly better than the traditional method as an assistive technology to aid in article screening. However, the efficiency of the platform significantly decreases as the complexity of the research question increases.

Conservative Treatment for Spontaneous Resolution of Postoperative Symptomatic Thoracic Spinal Epidural Hematoma-A Case Report.

Introduction: Postoperative epidural hematomas of the cervical and thoracic spine can pose a great risk of rapid neurological impairment and sometimes require immediate decompressive surgery. Case Report: We present the case of a young patient operated on for stabilization of a two-level thoracic vertebra fracture who developed total paralysis due to an epidural hematoma postoperatively. The course of epidural hematoma was quickly reversed with the help of a conservative technique that prevented revision surgery. The patient regained complete neurologic function very rapidly, and has been well on every follow-up to date. Conclusion: There is a role of similar maneuvers as described in this case to be employed in the management of postoperative epidural hematomas. However, prolonged watchful waiting should still be discouraged, and patients should remain ready for revision surgery if there are no early signs of rapid recovery.

Thematic trend mapping and hotspot analysis in bone marrow aspirate concentrate therapy: A scientometric literature analysis and advances in osteoarthritis.

Bone marrow aspirate concentrate (BMAC) therapy has been spotlighted as a promising regenerative tool with its abundant source of mesenchymal stromal cells (MSCs) and growth factors. The spectrum of the utility of BMAC therapy has been expanding day by day to harness the potential for varied therapeutic purposes. In the due course of its evolution, it is often essential to have a comprehensive summary of progress to have a greater understanding and refine our future directives. With technological developments such as data mining, graphic drawing and information analytics combined with computational statistics, visualization of scientific metrology has become a reality. With this newer perspective, we intend to use scientometric tools including text mining, cocitation analysis, keyword analysis and cluster network analysis to perform thematic trend mapping and hotspot analysis of the literature on BMAC therapy and evaluate its progress in the management of osteoarthritis.

How do I: Evaluate the safety and legitimacy of unproven cellular therapies?

BACKGROUND: Unproven cellular therapies are being offered to patients for a variety of conditions and diseases for which other treatments have failed. The use of untested cellular therapies is a worldwide problem. Practitioners (e.g., physicians, scientists, QA/QI facility managers, and policy advocates) are perhaps unaware of the risks involved with such therapies. Therefore, a critical need exists to bring attention to the potential limitations and adverse effects of these therapies to inform and limit misinformation. STUDY DESIGN AND METHODS: We describe the extent of the unproven cellular therapy problem through a search of scientific literature and social media coverage. We also describe the regulatory framework that can be used by the practitioner to review and evaluate both proven and unproven cellular therapies. RESULTS: We report on the current state of unproven cellular therapies across the globe. A workflow to facilitate an understanding of the regulatory processes involved in the approval of cellular therapies is provided as well as a list of warnings required by regulatory agencies on various products. It is hoped that this article will serve as a tool kit to educate the practitioner on navigating the field of unproven cellular therapy products. DISCUSSION: Increasing awareness of the issues associated with unproven therapies through education is important to help in reducing misinformation and risks to patients.

The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.

Current evidence on mesenchymal stem cell therapy for traumatic spinal cord injury: systematic review and meta-analysis.

BACKGROUND AIMS: The authors aim to analyze the evidence in the literature regarding the efficacy and safety of mesenchymal stem cell (MSC) therapy in human subjects with traumatic spinal cord injury (SCI) and identify its potential role in the management of SCI. METHODS: The authors conducted independent and duplicate searches of electronic databases, including PubMed, Embase and the Cochrane Library, until May 2020 for studies analyzing the efficacy and safety of stem cell therapy for SCI. American Spine Injury Association (ASIA) impairment scale (AIS) grade improvement, ASIA sensorimotor score, activities of daily living score, residual urine volume, bladder function improvement, somatosensory evoked potential (SSEP) improvement and adverse reactions were the outcomes analyzed. Analysis was performed in R platform using OpenMeta[Analyst] software. RESULTS: Nineteen studies involving 670 patients were included for analysis. On analysis, the intervention group showed statistically significant improvement in AIS grade (P < 0.001), ASIA sensory score (P < 0.017), light touch (P < 0.001), pinprick (P = 0.046), bladder function (P = 0.012), residual urine volume (P = 0.023) and SSEP (P = 0.002). However, no significant difference was noted in motor score (P = 0.193) or activities of daily living score (P = 0.161). Although the intervention group had a significant increase in complications (P < 0.001), no serious or permanent adverse events were reported. On subgroup analysis, low concentration of MSCs (<5 × 107 cells) and initial AIS grade A presentation showed significantly better outcomes than their counterparts. CONCLUSIONS: The authors' analysis establishes the efficacy and safety of MSC transplantation in terms of improvement in AIS grade, ASIA sensory score, bladder function and electrophysiological parameters like SSEP compared with controls, without major adverse events. However, further research is needed to standardize dose, timing, route and source of MSCs used for transplantation.

"Platelet-rich plasma holds promise in management of rheumatoid arthritis"-systematic review.

The treatment of rheumatoid arthritis (RA) has been closely evolving with an understanding of disease pathogenesis with disease modifying anti-rheumatoid drugs (DMARDS) and Biologic DMARDS being the main stay. platelet rich plasma (PRP) has been the center of research in many specialties in the past decade. Its ability to stop and reverse inflammation have attracted researchers to try PRP in RA. A systematic review of studies on PRP in RA is lacking. The study protocol was prospectively registered in PROSPERO. Detailed search of Cochrane, Scopus, Medline, Embase, and Web of science databases were made to identify the relevant articles till Sep 2020 following Cochrane and PRISMA guidelines. Number of subjects, Animal model used, cell lines used for the study, method of induction of arthritis, PRP dose, concentration used, frequency of administration and clinical, histologic, and molecular changes from baseline following PRP use were extracted and analysed. Eight studies were included for the review. Four of these were in-vitro studies. Two were exclusive animal studies. One study analysed the effects of PRP in RA in both animal models (mice) and Hela cell lines. One study was a report of a series of patients of resistant RA treated with PRP. In the in vitro studies while platelets increase the migration and invasion of RA-FLS, they suppressed the inflammation on the whole. Available animal studies and the Human study have shown encouraging results. There has been no evidence of exacerbation of inflammation in these studies. The quantity and quality of literature on the effects of PRP in treating joint pathologies in RA is limited. Preclinical studies show decrease in disease activity with good safety profile. Invitro studies show suppression of inflammation. Thus, the available literature is encouraging towards the use of PRP in RA. Larger trials and molecular studies to understand the exact role of platelets in disease pathogenesis and treatment mechanisms are needed to decide the future course of PRP in RA.

"Only 50% of randomized trials have high level of confidence in arthroscopy and sports medicine"-a spin-based assessment.

PURPOSE: Pioneering works on the quality appraisal of RCTs have recognized and addressed most of the issues that affect the RCT quality but some issues such as "Writers' bias" or "Spin" are yet to be sorted out. Spin, particularly in the abstracts, is a potential source of deception to the readers. The purpose of this study is to grade the RCTs of arthroscopy and sports medicine based on a spin in their abstracts, analyze the prevalence of spin, and explore methods to remove spin. METHODS: 250 recent RCTs from the top 5 arthroscopy and sports medicine journals were selected. Baseline data of the articles were collected. Consort Adherence Score (CAS) was calculated. The abstracts of the RCTs were graded using the Level Of Confidence (LOC) grading tool developed by the Orthopaedic Research Group. The association of the spin grade with other characteristics of the articles was analyzed. RESULTS: The median CAS for the included studies was 9 (IQR 8-10). It was found that only 49.6% (n = 124) articles had high LOC with no or one non-critical spin in the abstract. 20.8% (n = 52) had Moderate LOC with more than one non-critical spin. 19.6% (n = 49) had at least one critical spin and 10% (n = 25) had more than one critical flaw making their results have Low and Critically Low LOC, respectively. Of the ten variables analyzed in multivariate regression analysis, it was found that CAS was the only significant factor that determines the level of confidence in the abstract of RCTs CONCLUSION: Spin is prevalent in abstracts of sports medicine and arthroscopy journals with 50.4% having some form of spin. Grading the LOC of the RCTs based on spin is the necessity of the day for the readers. Only 49.6% of the RCTs had high LOC. Objective structuring of the abstracts would help eliminate spin in the future. LEVEL OF EVIDENCE: Level 1.

Risk-benefit analysis of wound drain usage in spine surgery: a systematic review and meta-analysis with evidence summary.

STUDY DESIGN: Systematic review, meta-analysis, evidence synthesis. OBJECTIVES: To analyse the literature evidence available to support the usage of wound drain in various scenarios of spine surgery and provide an evidence summary on the surgical practice. MATERIALS AND METHODS: We conducted independent and duplicate electronic database searches adhering to PRISMA guidelines in PubMed, Embase, and Cochrane Library till April 2020. Quality appraisal was done as per Cochrane ROB tool, and evidence synthesis was done as per GRADE approach. Five domains of spine surgery with associated key questions were identified. Evidence tables were generated for each question and critical appraisal done as per the GRADE approach. RESULTS: Twenty-three studies (9-RCTs, 4-prospective studies, 10-retrospective studies) were included. Analysis of studies in cervical spine either by anterior or posterior approach and single/multilevel thoracolumbar spinal surgeries did not show any evidence of reduction in surgical site infection (SSI) or haematoma formation with the use of drain. Deformity correction surgeries and surgeries done for trauma or tumour involving spine also did not find any added benefit from the use of wound drains despite increasing the total blood loss. CONCLUSION: Evidence from this review suggests that routine use of drain in various domains of spine surgery does not reduce the risk of SSI and their absence did not increase the risk of haematoma formation. The current best evidence is presented with its limitations. High-quality studies to address their use in spine surgeries in cervical, trauma, and tumour domains are required to further strengthen the evidence synthesised from available literature.

Pandemic response protocol of a non-frontline specialty in a multispecialty tertiary health care centre-a pilot model in orthopaedics.

BACKGROUND: 3,181,642 cases and 224,301 deaths in 212 regions of the world-this is the status of COVID-19 (Coronavirus Disease 2019) pandemic as of May 1, 2020. This pandemic has managed to overwhelm the health care system of the most advanced countries in the world. As the whole of the medical fraternity stands robed as health care professionals to fight against COVID-19, specialty emergencies like trauma continue to pester the already overburdened health care community. This situation calls for the need for a pandemic response protocol (PREP) in each specialty that helps the doctors to manage specialty emergencies without chaos and at the same time allowing them to play their part in pandemic management. CONCLUSION: PREP as an integrated pragmatic approach is essential in containing pandemics as they need international cooperation at various levels starting from knowledge sharing to monetary support. PREP which is in line with the WHO action plan, will be an essential minimum response of a non-frontline pandemic response specialty like orthopedics to combat and curtail the effects of a pandemic in a multispecialty tertiary health care centre.

Lateral clavicle fracture-plating options and considerations.

Clavicle fractures are among the most prevalent types of fractures with numerous treatment strategies that have evolved over time. In the realm of lateral-third clavicle fracture management, several surgical methods are available, with plate and screw constructs being one of the most frequently employed options. Within this construct, numerous choices exist for fixing the fracture. This editorial provides an overview of the common plate options utilized in the management of distal third clavicle fractures underscoring the critical considerations and approaches that guide clinicians in selecting the most appropriate fixation techniques, considering the complex landscape of clavicle fractures and their challenging management.

Tenosynovitis of hand: Causes and complications.

Tenosynovitis represents a common clinical condition characterized by inflammation of the synovium that encases the tendon sheath. Although tenosynovities may be noted in any tendon in the body, extremities such as hand, and foot remain the sites of high predilection to acquire this condition. The predominant cause of this predilection rests in the intricate tendon arrangements in these extremities that permit fine motor actions. This editorial explores the common causes and the complications associated with this condition to improve the understanding of the readers of this common condition encountered in our everyday clinical practice.

Bilateral erector spinae plane block for postoperative pain relief in lumbar spine surgery: A PRISMA-compliant updated systematic review & meta-analysis.

Study design: Systematic review. Objective: Erector spinae plane block (ESPB) is growing in popularity over the recent past as an adjuvant modality in multimodal analgesic management following lumbar spine surgery (LSS). The current updated meta-analysis was performed to analyze the efficacy of ESPB for postoperative analgesia in patients undergoing LSS. Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase and Cochrane Library till June 2023 for randomized controlled trials (RCTs) analyzing the efficacy of bilateral ESPB for postoperative pain relief in lumbar spine surgeries. Post-operative pain scores, total analgesic consumption, first analgesic requirement time, length of stay and complications were the outcomes evaluated. Statistical analysis was performed using STATA 17 software. Results: 32 RCTs including 1464 patients (ESPB/Control = 1077/1069) were included in the analysis. There was a significant pain relief in ESPB group, as compared to placebo across all timelines such as during immediate post-operative period (p < 0.001), 4 h (p < 0.001), 8 h (p < 0.001), 12 h (p < 0.001), 24 h (p = 0.001) post-surgery. Similarly, ESPB group showed a significant reduction in analgesic requirement at 8 h (p < 0.001), 12 h (p = 0.001), and 24 h (p < 0.001). However, no difference was noted in the first analgesic requirement time, time to ambulate or total length of stay in the hospital. ESPB demonstrated significantly improved overall satisfaction score for the analgesic management (p < 0.001), reduced intensive care stay (p < 0.05) with significantly reduced post-operative nausea and vomiting (p < 0.001) compared to controls. Conclusion: ESPB offers prolonged post-operative pain relief compared to controls, thereby reducing the need for opioid consumption and its related complications.

Does progress in microfracture techniques necessarily translate into clinical effectiveness?

BACKGROUND: Multitudinous advancements have been made to the traditional microfracture (MFx) technique, which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of cartilage defect. The relative benefits and pitfalls of these diverse modifications of MFx technique are still not widely understood. AIM: To comparatively analyze the functional, radiological, and histological outcomes, and complications of various generations of MFx available for the treatment of cartilage defects. METHODS: A systematic review was performed using PubMed, EMBASE, Web of Science, Cochrane, and Scopus. Patients of any age and sex with cartilage defects undergoing any form of MFx were considered for analysis. We included only randomized controlled trials (RCTs) reporting functional, radiological, histological outcomes or complications of various generations of MFx for the management of cartilage defects. Network meta-analysis (NMA) was conducted in Stata and Cochrane's Confidence in NMA approach was utilized for appraisal of evidence. RESULTS: Forty-four RCTs were included in the analysis with patients of mean age of 39.40 (± 9.46) years. Upon comparing the results of the other generations with MFX-I as a constant comparator, we noted a trend towards better pain control and functional outcome (KOOS, IKDC, and Cincinnati scores) at the end of 1-, 2-, and 5-year time points with MFx-III, although the differences were not statistically significant (P > 0.05). We also noted statistically significant Magnetic resonance observation of cartilage repair tissue score in the higher generations of microfracture (weighted mean difference: 17.44, 95% confidence interval: 0.72, 34.16, P = 0.025; without significant heterogeneity) at 1 year. However, the difference was not maintained at 2 years. There was a trend towards better defect filling on MRI with the second and third generation MFx, although the difference was not statistically significant (P > 0.05). CONCLUSION: The higher generations of traditional MFx technique utilizing acellular and cellular components to augment its potential in the management of cartilage defects has shown only marginal improvement in the clinical and radiological outcomes.

Delay in Time to Diagnosis of Idiopathic Transient Osteoporosis of the Hip with Radiographs: Diagnostic Insights from a Series of 10 Cases.

Introduction: Transient osteoporosis of the hip (TOH) is a poorly recognized self-limiting clinical entity. Due to a lack of awareness among the clinicians, the condition is often misdiagnosed leading to inappropriate treatment, thereby lengthening the time to diagnosis (TTD). In this study, we analyze the delay in TTD of TOH using plain radiographs and present the optimal management strategy. Case Report: We retrospectively collected the data of patients who were diagnosed with TOH from March 2017 to March 2022. A total of 10 patients with a mean age of 43.7 years (range 33-56 years) were included in the study. The mean time to presentation from the onset of symptoms was 4 weeks (range 2-8 weeks) Radiologic evaluation with radiographs was sensitive in only 8 patients with osteopenia, whereas magnetic resonance imaging (MRI) was sensitive in all the patients and aided in early diagnosis of TOH. Radiographic evaluation alone leads to a mean delay in TTD of 1.6 weeks (range 0-8 weeks) in our study. All the patients were treated conservatively without any major complications. Conclusion: Plain radiographs were not sensitive in the early detection of TOH and increased the TTD by 1.6 weeks, however, MRI imaging was found to be highly sensitive and specific in diagnosing TOH.

Beginning of the era of Organ-on-Chip models in osteoarthritis research.

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the progressive breakdown of joint cartilage and underlying bone, affecting millions globally. Traditional research models, including in-vitro cell cultures and in-vivo animal studies, have provided valuable insights but exhibit limitations in replicating the complex human joint environment. This review article focuses on the transformative role of Organ-on-Chip (OoC) and Joint-on-Chip (JoC) technologies in OA research. OoC and JoC models, rooted in microfluidics, integrate cellular biology with engineered environments to create dynamic, physiologically relevant models that closely resemble human tissues and organs. These models enable an accurate depiction of pathogenesis, offering deeper insights into molecular and cellular mechanisms driving the disease. This review explores the evolution of OoC technology in OA research, highlighting its contributions to disease modeling, therapeutic discovery, and personalized medicine. It delves into the design concepts, fabrication techniques, and integration strategies of joint components in JoC models, emphasizing their role in accurately mimicking joint tissues and facilitating the study of intricate cellular interactions. The article also discusses the significant advancements made in OA research through published JoC models and projects the future scope of these technologies, including their potential in personalized medicine and high-throughput drug screening. The evolution of JoC models signifies a paradigm shift in OA research, offering a promising path toward more effective and targeted therapeutic strategies.

Next Generation Sequencing in orthopaedic infections - Where is the road headed?

Next-generation sequencing (NGS) has emerged as a game changer in the field of orthopaedic diagnostics, notably in the detection and management of infections associated with prosthetic joints and implants. This paper conducts an exhaustive examination of the pivotal role, outcomes, and prospective future uses of NGS in diagnosing orthopaedic infections. In comparison to conventional culture-based methods, NGS offers a marked improvement in sensitivity thereby facilitating prompt and comprehensive identification of pathogens. This encompasses the ability to detect polymicrobial infections, antibiotic-resistant strains, and previously imperceptible microorganisms. Furthermore, this article delves into the technology's contribution to advancing personalized medicine and promoting judicious antibiotic use. Nonetheless, the seamless integration of NGS into routine clinical practice is impeded by challenges such as substantial financial outlays, the requisite for specialized equipment and expertise, and the intricacy associated with data analysis. Notwithstanding these impediments, the potential for NGS to revolutionize orthopaedic diagnostics remains substantial, with ongoing advancements poised to address current limitations and broaden its scope within clinical applications.