Mesenchymal stromal cell therapy for patients with rheumatoid arthritis.

Management of relapses and refractory rheumatoid arthritis (RA) patients is complex and difficult. Even after the administration of new biological disease-modifying anti-rheumatic drugs (DMARDs), only a few patients achieve the complete remission phase. DMARDs help only in modifying the disease activity, which sooner or later fails. They do not manage the disease at the patho-etiological level. There are some serious side effects as well as drug interaction with DMARDs. There are few subsets of RA patients who do not respond to DMARDs, reasons unknown. Mesenchymal stem cells (MSCs) provide a promising alternative, especially in such cases. This review elaborates on the studies pertaining to the application of MSCs in rheumatoid arthritis over the last two decades. A total of 14 studies (one review article) including 447 patients were included in the study. Most of the studies administered MSCs in refractory RA patients through the intravenous route with varied dosages and frequency of administration. MSCs help in RA treatment via various mechanisms including paracrine effects. All the studies depicted a better clinical outcome with minimal adverse events. The functional scores including the VAS scores improved significantly in all studies irrespective of dosage and source of MSCs. The majority of the studies depicted no complications. Although the use of MSCs in RA is still in the early stages requiring further refinement in the source of MSCs, dosage, and frequency. The role of MSCs in the management of RA has a promising prospect. MSCs target the RA at the molecular level and has the potential to manage refractory RA cases not responding to conventional treatment. Multicentric, large sample populations, and long-term studies are required to ascertain efficacy and safety.

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.

"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.

A Novel Mohs Precision Tool.

BACKGROUND: Effective treatment by Mohs micrographic surgery requires preparation of high-quality slides. OBJECTIVE: To examine a novel tissue alignment device designed to address variability in tissue processing because of excessive sample trimming. MATERIALS AND METHODS: A device was designed to account for angular errors and unparalleled tissue embedding. A retrospective chart review was performed both with and without the use of the device over the course of a 4-year period (2012-2015). RESULTS: Between January 1, 2012, and June 10, 2014, before device implementation, mean number of stages per case was 1.65 (n = 3,680) and mean number of surgeries per day was 6.34 (n = 640). Between June 11, 2014, and October 02, 2015, with device implemented, the average number of stages per case between decreased to 1.58 (n = 2,562) and the number of daily surgeries increased to 7.05 (n = 358). This represents a significant decrease in number of stages per case by 0.07 stages (95% CI: -0.01 to -0.13, p = .02), as well as an increase in the number of cases per day by 0.71 cases (95% CI: 0.12-1.3, p < .01). CONCLUSION: Slide preparation using the novel alignment device may result in less tissue waste and more cases being performed daily.

Safety and Efficacy of Bone-Marrow Aspirate Concentrate in Hip Osteoarthritis: A Systematic Review of Current Clinical Evidence.

Introduction: Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years. Conventional treatment modalities have limitations and side-effects. To overcome these limitations, over the last decade, there has been an increased interest in the use of orthobiologics derived from autologous sources including platelet-rich plasma (PRP), bone-marrow aspirate concentrate (BMAC) and adipose tissue derived formulations. This review qualitatively presents the in-vitro, pre-clinical, clinical and on-going clinical studies exploring the safety and efficacy of BMAC for management of hip OA. Materials and methods: The electronic database search was done through PubMed, Embase, Web of Science, Scopus, ProQuest and Google Scholar till February 2024. The search terms used were "osteoarthritis" OR "hip osteoarthritis" OR "orthobiologics" OR "efficacy or use of orthobiologic treatment" OR "bone-marrow concentrate" OR "bone-marrow aspirate concentrate", AND "BMAC". The inclusion criteria were clinical studies of any level of evidence written in the English language, published till February 2024, evaluating the safety and efficacy of intra-articular administration of BMAC for the management of hip OA. Results: A total of 5 studies were included in this review for qualitative data synthesis. The total number of patients who participated in the study was 182, ranging from 4 to 112 in a single study. No adverse events were reported throughout the duration of the study. In addition, intra-articular administration of BMAC led to reduced pain, and improved function and overall quality of life (QoL). Conclusion: The results from this review demonstrated that administration of BMAC is safe and potentially efficacious in terms of reducing pain, improving function and overall QoL of patients with hip OA in short- and mid-term average follow-up based on the included studies. Nonetheless, more adequately powered, multi-center, prospective, double-blind, non-randomized and randomized controlled trials with long-term follow-up are warranted to establish long-term safety and efficacy of BMAC for management of hip OA and justify its routine clinical use.

Metabolomics in Osteoarthritis Knee: A Systematic Review of Literature.

Introduction: Osteoarthritis (OA) is a common degenerative disorder of the synovial joints and is usually an age-related disease that occurs due to continuous wear and tear of the cartilage in the joints. Presently, there is no proven medical management to halt the progression of the disease in the early stages. The purpose of our systematic review is to analyze the possible metabolites and metabolic pathways that are specifically involved in OA pathogenesis and early treatment of the disease. Materials and Methods: The articles were collected from PubMed, Cochrane, Google Scholar, Embase, and Scopus databases. "Knee", "Osteoarthritis", "Proteomics", "Lipidomics", "Metabolomics", "Metabolic Methods", and metabolic* were employed for finding the articles. Only original articles with human or animal OA models with healthy controls were included. Results: From the initial screening, a total of 458 articles were identified from the 5 research databases. From these, 297 articles were selected in the end for screening, of which 53 papers were selected for full-text screening. Finally, 50 articles were taken for the review based on body fluid: 6 urine studies, 15 plasma studies, 16 synovial fluid studies, 11 serum studies, 4 joint tissue studies, and 1 fecal study. Many metabolites were found to be elevated in OA. Some of these metabolites can be used to stage the OA Three pathways that were found to be commonly involved are the TCA cycle, the glycolytic pathway, and the lipid metabolism. Conclusion: All these studies showed a vast array of metabolites and metabolic pathways associated with OA. Metabolites like lysophospholipids, phospholipids, arginine, BCCA, and histidine were identified as potential biomarkers of OA but a definite association was not identified, Three pathways (glycolytic pathway, TCA cycle, and lipid metabolic pathways) have been found as highly significant in OA pathogenesis. These metabolic pathways could provide novel therapeutic targets for the prevention and progression of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01169-5.

GOLDIC Therapy Holds Promise as an Orthobiologic Agent: A Systematic Review of the Literature.

Introduction: Orthobiologic agents play a significant role in regenerative medicine. The quest for newer and more effective Orthobiologic agents is never-ending, leading to the evolution of more reformed products. GOLDIC (GOLD Induced cytokine) is a recently evolving Orthobiologic agent developed by conditioning autologous serum with gold particles. We aim to collate the available evidence on GOLDIC and provide a systematic literature review. Materials and methods: Using Cochrane and PRISMA guidelines literature search was done for GOLDIC. After duplicate removal and exclusions, 62 articles were scrutinized, of which 8 articles qualified for full-text review. A risk-of-bias assessment of the included studies was done. Results: All articles showed standardized preparation methods of GOLDIC and uniformity in the number of doses administered, except one study. Reproducible results were noted like an increase in plasma gelsolin and improved KOOS, WOMAC, and VAS scores. Conclusion: GOLDIC has the potential to be a significant Orthobiologic modality considering its standardized preparation techniques, method of administration, and uniformly reproducible outcome measures. However, further high-quality evidence is needed to analyze the clinical efficiency and safety profile of GOLDIC. Systematic review registration: INPLASY202350027 [https://doi.org/10.37766/inplasy2023.5.0027].

Barriers and facilitators of adherence to medical advice on skin self-examination during melanoma follow-up care.

BACKGROUND: Melanoma is the fastest growing tumor of the skin, which disproportionately affects younger and middle-aged adults. As melanomas are visible, recognizable, and highly curable while in early stages, early diagnosis is one of the most effective measures to decrease melanoma-related mortality. Skin self-examination results in earlier detection and removal of the melanoma. Due to the elevated risk of survivors for developing subsequent melanomas, monthly self-exams are strongly recommended as part of follow-up care. Yet, only a minority of high-risk individuals practices systematic and regular self-exams. This can be improved through patient education. However, dermatological education is effective only in about 50% of the cases and little is known about those who do not respond. In the current literature, psychosocial variables like distress, coping with cancer, as well as partner and physician support are widely neglected in relation to the practice of skin self-examination, despite the fact that they have been shown to be essential for other health behaviors and for adherence to medical advice. Moreover, the current body of knowledge is compromised by the inconsistent conceptualization of SSE. The main objective of the current project is to examine psychosocial predictors of skin self-examination using on a rigorous and clinically sound methodology. METHODS/DESIGN: The longitudinal, mixed-method study examines key psychosocial variables related to the acquisition and to the long-term maintenance of skin self-examination in 200 patients with melanoma. Practice of self-exam behaviors is assessed at 3 and 12 months after receiving an educational intervention designed based on best-practice standards. Examined predictors of skin self-exam behaviors include biological sex, perceived self-exam efficacy, distress, partner and physician support, and coping strategies. Qualitative analyses of semi-structured interviews will complement and enlighten the quantitative findings. DISCUSSION: The identification of short and long-term predictors of skin self-examination and an increased understanding of barriers will allow health care professionals to better address patient difficulties in adhering to this life-saving health behavior. Furthermore, the findings will enable the development and evaluation of evidence-based, comprehensive intervention strategies. Ultimately, these findings could impact a wide range of outreach programs and secondary prevention initiatives for other populations with increased melanoma risk.

Repair of a multi-subunit defect of the nasal ala, perialar cheek, and apical triangle of the upper lip.

A 67-year-old female was treated for a left nasal ala basal cell carcinoma; post-Mohs defect was 1.5 × 1.5 cm and extended to involve the perialar cheek and apical triangle of the upper lip. How would you repair this defect?

Adhesive Capsulitis of Hip-A Systematic Review of Literature.

Introduction: Adhesive capsulitis is clinically characterized by the gradual progressive painful loss of active and passive motion caused by the formation of adhesions of the joint capsule. Adhesive Capsulitis of the Hip (ACH) is not a well-explored clinical condition when compared to adhesive capsulitis of shoulder because of the underdiagnosis and rarity of this condition. Materials and Methods: Cochrane, Scopus, Pubmed, Embase, and Web of Science databases were searched for original studies on ACH till December 2021 following Cochrane and PRISMA guidelines. Year of publication, authors, number of cases, baseline characteristics of the studies, causes described, presentation, associated conditions, method of diagnosis, treatment to be given, functional outcomes, and complications was extracted from each study. Results: 16 articles were included in this review. 3 of the included studies were retrospective case-control studies, 6 were case series and the remaining 7 were case reports. A total of 224 ACH cases were recorded. Pain and stiffness of the hips were the most common clinical features. Investigations like serology, radiograph, and MRI have been used to rule out other conditions. Arthrography has been used to confirm the diagnosis in 7 studies. Spontaneous recovery is expected in one to two years. Management has been in the form of physiotherapy, intra-articular injection, and arthroscopy. Conclusion: Literature on ACH is limited because of the rarity of the condition. The disease has a favorable prognosis with the possibility of spontaneous recovery. Physiotherapy has been the first line of management. Intractable cases require surgical intervention. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00808-z.

Antimicrobial Effects of Platelet-Rich Plasma and Platelet-Rich Fibrin: A Scoping Review.

Platelet-rich plasma (PRP), derived from the centrifugation and subsequent separation of whole blood, results in an unusually high concentration of platelets. A newer form of platelet concentrate, platelet-rich fibrin (PRF), has also been developed. There has been significant research into the therapeutic effects of PRP, particularly in enhancing wound healing and preventing infections in surgical wounds. This scoping review aims to thoroughly evaluate preclinical and clinical evidence regarding the antimicrobial effects of PRP and PRF. In conducting this review, 612 records were examined, and 36 articles were selected for inclusion. The studies reviewed include preclinical research, such as in-vitro and in-vivo studies, and clinical trials involving human participants. The current clinical evidence suggests a notable trend towards the antimicrobial capabilities of PRP and PRF, underscoring their potential benefits in treating wounds. The application of PRP and PRF in wound management shows encouraging outcomes, but further investigation is needed to optimize their use as antimicrobial agents. Additional research, particularly randomized controlled trials, is essential to substantiate their antimicrobial effectiveness in specific diseases and types of wounds, considering their potential impact on clinical results.

Medico-Legal Implications and Regulatory Frameworks of Regenerative Orthopaedics.

Regenerative orthopaedics has revolutionized traditional medicine, which represents a giant leap in science and research. The knowledge of the medico-legal implications and regulatory framework of this branch is vital for clinicians and researchers to go forward smoothly. This systematic review of the literature should shed light on these considerations and provide a comprehensive knowledge of the various implications and laws governing practice and research. The wide plethora of knowledge in the use of regenerative orthopaedics should be complemented by updated regulations and clinicians' grasp of knowledge on regenerative medicine. The review focused on peer-reviewed published articles concerned with the topic and outlined common medico-legal issues and the current regulatory frameworks in various countries. The articles suggest that developed nations like the US have faced several lawsuits in this field, and a few countries in Europe like Italy and Germany, which were frontrunners in this field based on research, have fallen back due to emerging legal and regulatory policies. Undoubtedly, regenerative orthopaedics holds the key to future orthopaedics, but the world is skeptical of this concept, and laws and regulatory frameworks can curb it if not guided well. In India, this field has received prime attention, but at a slow pace when compared to the laws. After reviewing 113 articles, we analysed eight critically in this systematic review to emphasize the comparative global frameworks, daily medico-legal problems, and solutions for the branch of regenerative orthopaedics.

Is mandible derived mesenchymal stromal cells superior in proliferation and regeneration to long bone-derived mesenchymal stromal cells?

Mesenchymal stromal cells (MSCs) are cells with the characteristic ability of self-renewal along with the ability to exhibit multilineage differentiation. Bone marrow (BM) is the first tissue in which MSCs were identified and BM-MSCs are most commonly used among various MSCs in clinical settings. MSCs can stimulate and promote osseous regeneration. Due to the difference in the development of long bones and craniofacial bones, the mandibular-derived MSCs (M-MSCs) have distinct differentiation characteristics as compared to that of long bones. Both mandibular and long bone-derived MSCs are positive for MSC-associated markers such as CD-73, -105, and -106, stage-specific embryonic antigen 4 and Octamer-4, and negative for hematopoietic markers such as CD-14, -34, and -45. As the M-MSCs are derived from neural crest cells, they have embryogenic cells which promote bone repair and high osteogenic potential. In vitro and in vivo animal-based studies demonstrate a higher rate of proliferation and high osteogenic potential for M-MSCs as compared to long-bones MSCs, but in vivo studies in human subjects are lacking. The BM-MSCs have their advantages and limitations. M-MSCs may be utilized as an alternative source of MSCs which can be utilized for tissue engineering and promoting the regeneration of bone. M-MSCs may have potential advantages in the repair of craniofacial or orofacial defects. Considering the utility of M-MSCs in the field of orthopaedics, we have discussed various unresolved questions, which need to be explored for their better utility in clinical practice.

Beyond the Pain: A Systematic Narrative Review of the Latest Advancements in Fibromyalgia Treatment.

Fibromyalgia is a complex chronic pain disorder that significantly impacts the quality of life of affected individuals. The etiology of fibromyalgia remains elusive, necessitating effective treatment options. This review aims to provide an overview of current treatment options for fibromyalgia and highlight recent updates in managing the condition. The methodology employed in this systematic review comprised the following key steps. We conducted a comprehensive search across various databases to identify pertinent studies published between 2000 and 2023. Inclusion criteria were defined to specifically target studies involving adult individuals diagnosed with fibromyalgia, with a focus on both pharmacological and non-pharmacological interventions for managing the condition. The review encompassed a range of study types, including randomized controlled trials, observational studies, and systematic reviews. To ensure the quality of the selected studies, we employed appropriate assessment tools, and data extraction and synthesis adhered to established guidelines. This rigorous approach allowed for a robust analysis of the literature on fibromyalgia management. In the course of our review, it became evident that a spectrum of treatment approaches holds significant promise in the management of fibromyalgia. Specifically, pharmacological interventions, including selective serotonin-norepinephrine reuptake inhibitors, anticonvulsants, cannabinoids, tropisetron, and sodium oxybate, have exhibited substantial potential in alleviating fibromyalgia symptoms. Concurrently, non-pharmacological strategies, such as cognitive-behavioral therapy, exercise regimens, and complementary and alternative therapies, have yielded positive outcomes in improving the condition's management. Recent developments in the field have introduced innovative pharmacological agents like milnacipran and pregabalin, in addition to non-pharmacological interventions like mindfulness-based stress reduction and aquatic exercise, expanding the array of options available to enhance fibromyalgia care and alleviating patient symptoms. Fibromyalgia necessitates a multidisciplinary approach to treatment, encompassing both pharmacological and non-pharmacological interventions. Recent updates in fibromyalgia management offer additional options to alleviate symptoms and improve the quality of life for individuals with fibromyalgia. Healthcare professionals should remain informed about these advancements to provide evidence-based care, addressing the complex symptoms associated with fibromyalgia and enhancing patient outcomes.

Machine learning and deep neural network-based learning in osteoarthritis knee.

Osteoarthritis (OA) of the knee joint is considered the commonest musculoskeletal condition leading to marked disability for patients residing in various regions around the globe. Application of machine learning (ML) in doing research regarding OA has brought about various clinical advances viz, OA being diagnosed at preliminary stages, prediction of chances of development of OA among the population, discovering various phenotypes of OA, calculating the severity in OA structure and also discovering people with slow and fast progression of disease pathology, etc. Various publications are available regarding machine learning methods for the early detection of osteoarthritis. The key features are detected by morphology, molecular architecture, and electrical and mechanical functions. In addition, this particular technique was utilized to assess non-interfering, non-ionizing, and in-vivo techniques using magnetic resonance imaging. ML is being utilized in OA, chiefly with the formulation of large cohorts viz, the OA Initiative, a cohort observational study, the Multi-centre Osteoarthritis Study, an observational, prospective longitudinal study and the Cohort Hip & Cohort Knee, an observational cohort prospective study of both hip and knee OA. Though ML has various contributions and enhancing applications, it remains an imminent field with high potential, also with its limitations. Many more studies are to be carried out to find more about the link between machine learning and knee osteoarthritis, which would help in the improvement of making decisions clinically, and expedite the necessary interventions.

Factors Influencing the Yield of Progenitor Cells in Bone Marrow Aspiration Concentrate-A Retrospective Analysis of 58 Patients.

This study aims to identify the role of subjective factors (age, sex, and comorbidities) and procedure-specific factors (aspiration volume) in influencing the yield of progenitor cells in bone marrow aspiration concentrate (BMAC) harvested from the iliac crest. A retrospective analysis was conducted on 58 patients (male:female = 31:27; mean age: 52.56 ± 18.14 years) who underwent BMAC therapy between January 2020 and June 2021. The factors analyzed include individual factors such as age, sex, and comorbid conditions, and procedural factors such as aspirate volume. The mononuclear cell (MNC) count and colony-forming unit (CFU) assay were used to assess the yield of progenitors in the aspirate. Pearson's correlation test was performed for the age, aspirate volume, and outcome parameters, such as MNC and CFU. We used the chi-square test to analyze the role of sex and comorbidities on cellular yield. The mean volume of aspirate used for BMAC therapy was 66.65 (±17.82) mL. The mean MNC count of the BMAC was 19.94 (±16.34) × 106 cells, which formed 11 (±12) CFUs. Evidence of statistically significant positive associations was noted between the CFUs developed from the BMAC and the MNC count within them (r = 0.95, p < 0.001). The sex of the individual did not play any significant role in MNC count (p = 0.092) or CFUs formed (p = 0.448). The age of the individual showed evidence of a statistically significant negative association with the MNC count (r = -0.681, p < 0.001) and CFUs (r = -0.693, p < 0.001), as did the aspiration volume with the MNC count (r = -0.740, p < 0.001) and CFUs (r = -0.629, p < 0.001). We also noted a significant reduction in the MNC count (p = 0.002) and CFUs formed (p = 0.004) when the patients presented comorbidities. Individual factors such as age, comorbid conditions, and procedure factors such as aspirate volume significantly affected the yield of progenitor cells in the BMAC. The sex of the individual did not influence the yield of progenitor cells in BMAC.

Stem Cell Therapy in Critical Limb Ischemia.

Critical limb ischemia (CLI), a serious outcome of peripheral artery disease, is frequently associated with morbid outcomes. The available treatment modalities do not provide satisfactory results, leading to marked morbidities such as joint contracture and amputations, resulting in a high economic burden. The peripheral vascular disease tends to cause more morbidity in patients with diabetes and atherosclerosis, given the pre-existing compromised perfusion of medium and small vessels in diabetic patients. With surgical procedures, the chance of vascular compromise further increases, inducing a significantly greater rate of amputation. Hence, the need for nonsurgical treatment modalities such as stem cell therapy (SCT), which promotes angiogenesis, is warranted. In CLI, SCT acts through neovascularization and the development of collateral arteries, which increases blood supply to the soft tissues of the ischemic limb, providing satisfactory outcomes. An electronic database search was performed in PubMed, SCOPUS, EMBASE, and ScienceDirect to identify published clinical trial data, research studies, and review articles on stem cell therapy in critical limb ischemia. The search resulted in a total of 2391 results. Duplicate articles screening resulted in 565 articles. In-depth screening of abstracts and research titles excluded 520 articles, yielding 45 articles suitable for full-text review. On review of full text, articles with overlapping and similar results were filtered, ending in 25 articles. SCT promotes arteriogenesis, and bone marrow-derived mesenchymal stromal cells produce significant effects like reduced morbidity, improved amputation-free survival (AFS ) rate, and improved distal perfusion even in "no-option" CLI patients. SCT is a promising treatment modality for CLI patients, even in those in whom endovascular and revascularization procedures are impossible. SCT assures a prolonged AFS rate, improved distal perfusion, improved walking distances, reduced amputation rates, and increased survival ratio, and is well-tolerated.

Comparative effectiveness of adipose-derived mesenchymal stromal cells in the management of knee osteoarthritis: A meta-analysis.

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder, is associated with an increasing socioeconomic impact owing to the ageing population. AIM: To analyze and compare the efficacy and safety of bone-marrow-derived mesenchymal stromal cells (BM-MSCs) and adipose tissue-derived MSCs (AD-MSCs) in knee OA management from published randomized controlled trials (RCTs). METHODS: Independent and duplicate electronic database searches were performed, including PubMed, EMBASE, Web of Science, and Cochrane Library, until August 2021 for RCTs that analyzed the efficacy and safety of AD-MSCs and BM-MSCs in the management of knee OA. The visual analog scale (VAS) score for pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Tegner score, magnetic resonance observation of cartilage repair tissue score, knee osteoarthritis outcome score (KOOS), and adverse events were analyzed. Analysis was performed on the R-platform using OpenMeta (Analyst) software. Twenty-one studies, involving 936 patients, were included. Only one study compared the two MSC sources without patient randomization; hence, the results of all included studies from both sources were pooled, and a comparative critical analysis was performed. RESULTS: At six months, both AD-MSCs and BM-MSCs showed significant VAS improvement (P = 0.015, P = 0.012); this was inconsistent at 1 year for BM-MSCs (P < 0.001, P = 0.539), and AD-MSCs outperformed BM-MSCs compared to controls in measures such as WOMAC (P < 0.001, P = 0.541), Lysholm scores (P = 0.006; P = 0.933), and KOOS (P = 0.002; P = 0.012). BM-MSC-related procedures caused significant adverse events (P = 0.003) compared to AD-MSCs (P = 0.673). CONCLUSION: Adipose tissue is superior to bone marrow because of its safety and consistent efficacy in improving pain and functional outcomes. Future trials are urgently warranted to validate our findings and reach a consensus on the ideal source of MSCs for managing knee OA.

Is Platelet-Rich Plasma Effective in Enhancing Spinal Fusion? Systematic Overview of Overlapping Meta-Analyses.

STUDY DESIGN: Systematic review. OBJECTIVES: We performed this systematic overview on overlapping meta-analyses that analyzed the role of platelet-rich plasma(PRP) in enhancing spinal fusion and identify which study provides the current best evidence on the topic and generate recommendations for the same. MATERIALS AND METHODS: We conducted independent and duplicate electronic database searches in PubMed, Web of Science, Embase, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects till October-2020 for meta-analyses that analyzed the role of PRP in spinal fusion procedures. Methodological quality assessment was made using Oxford Levels of Evidence, AMSTAR scoring, and AMSTAR 2 grades. We then utilized the Jadad decision algorithm to identify the study with highest quality to represent the current best evidence to generate recommendations. RESULTS: 3 meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of included studies varied from 5-8(mean:6.3) and all included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades. The current best evidence showed that utilization of PRP was not associated with significant improvement in patient-reported outcomes such as Visual Analog Score for pain compared to the standard fusion procedure. Moreover, PRP was found to be associated with lower fusion rates. CONCLUSION: Based on this systematic overview, the effectiveness of PRP as a biological agent in augmenting spinal fusion is limited. Current evidence does not support the use of PRP as an adjuvant to enhance spinal fusion.

Does vehicle-based delivery of mesenchymal stromal cells give superior results in knee osteoarthritis? Meta-analysis of randomized controlled trials.

STUDY DESIGN: Meta-analysis. OBJECTIVES: We aim to analyze and compare the efficacy and safety of vehicle-based delivery of Mesenchymal Stromal Cells (MSCs) in the management of osteoarthritis of the knee from Randomized Controlled Trials (RCTs) available in the literature. MATERIALS AND METHODS: We conducted independent and duplicate electronic database searches including PubMed, Embase, Web of Science, and Cochrane Library till August 2021 for RCTs analyzing the efficacy and safety of vehicle-based delivery of MSCs in the management of knee osteoarthritis. Visual Analog Score (VAS) for Pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta [Analyst] software. RESULTS: 21 studies involving 936 patients were included for analysis. None of the studies made a direct comparison of the direct and vehicle-based delivery of MSCs, hence we pooled the results of all the included studies of both groups and made a comparative analysis of their outcomes. Although at 6 months, both direct and vehicle-based delivery of MSCs showed significantly better VAS improvement (p = 0.002, p = 0.010), it was not consistent at 1 year for the vehicle delivery (p = 0.973). During 6 months and 12 months, direct delivery of MSCs (p < 0.001, p < 0.001) outperformed vehicle delivery (p = 0.969, p = 0.922) compared to their control based on WOMAC scores respectively. Both direct (p = 0.713) and vehicle-based delivery (p = 0.123) of MSCs did not produce significant adverse events compared to their controls. CONCLUSION: Our analysis of literature showed that current clinically employed methods of vehicle-based delivery of MSCs such as platelet-rich plasma, hyaluronic acid did not demonstrate superior results compared to direct delivery, concerning the efficacy of treatment measured by improvement in pain, functional outcomes, and safety. Hence, we urge future clinical trials to be conducted to validate the effectiveness of advanced delivery vehicles such as composite bioscaffolds to establish their practical utility in cartilage regeneration with respect to its encouraging in-vitro evidence.