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.

Journal metrics of the top-ranked Orthopaedic, Medical, and Surgical journals - A cross-sectional, comparative study.

PURPOSE: In academic publishing, research metrics play a crucial role in assessing the scientific impact and performance of the published literature, as well as of the journals in which they are published. Several journal-level metrics (JLM) such as the h-index of the analysed journals, total citations, total documents, citable documents, references and external citations per document are considered crucial indicators of the importance and reputation of the journals. We hypothesize that journals in the field of Medicine receive more citations than those in Surgical journals like Orthopaedic surgery, and hence have better JLM. This study aims to to assess and compare the JLM of Medical and Surgical journals between two time zones 2017-2019 vs. 2020-2022, i.e., pre and post-COVID-19 pandemic period. METHODS: A cross-sectional bibliometric analysis of the top-ranked Orthopaedic, Medical, and Surgical journals was undertaken based on traditional JLM, using the SCImago database from 2017 to 2022. Our analysis focused on identifying trends in the h-index of the analysed journals, total citations, total documents, citable documents, references and external citations per document. RESULTS: Overall Medical journals were found to have higher JLM than the Surgical and Orthopaedic journals. The h-index of Surgical journals, Medical journals and Orthopaedic journals were comparable between the two periods (pre and -post-COVID-19 pandemic); Total Cites (3 years), total documents (2017), total documents (3 years), total references, and citable documents (3 years) of Surgical journals, Medical journals and Orthopaedic journals were significantly higher in the period 2020-2022. CONCLUSION: There has been a steady increase in the number of publications from post COVID-19 period. Medical journals have higher JLM than Surgical and Orthopaedic journals. Journal of Bone and Joint Surgery (Am), Annals of Surgery and Diabetes Care were the most published journals in Orthopaedics, General Surgery and Medicine-related topics respectively.

Negative pressure wound therapy in the management of postoperative spinal wound infections: a systematic review.

INTRODUCTION: Postoperative wound infection after spinal surgery might be a challenge to manage. A wide range of procedures have been described for managing infected spinal wounds. An increasingly common procedure in the management of surgical site infections (SSI) is negative pressure wound therapy (NPWT), also known as vacuum-assisted closure. As there is a paucity of clear clinical advice the present investigation aims to update current evidence on the use of NPWT to manage postoperative SSI occurring after instrumented spine surgery. METHODS: This systematic review was conducted according to the preferred reporting Items for systematic reviews and meta-analyses: the 2020 PRISMA statement. In January 2024, the following databases were accessed: PubMed, Web of Science, and Google Scholar. No time constraint was set for the search. All the clinical studies investigating the unique use of NPWT in treating postoperative spinal wound infections were accessed. RESULTS: A total of 381 patients were included in the present study. Of them 52.5% (200 of 381 patients) were women. The mean age was 52.2 ± 15.2 years. The average length of the NPWT was 21.2 days (range 7-90 days). CONCLUSION: NPWT could be a valuable adjuvant therapy for the management of SSI after spine surgery. Additional high-quality investigations are required to assess the efficacy and safety of NPWT in SSI after spine surgery, especially if combined with contraindications or risk factors, such as the presence of intraoperative CSF leak. LEVEL OF EVIDENCE: Level IV, Systematic review.

Whole-body cryotherapy in orthopaedics: current concepts.

The use of whole-body cryotherapy (WBC) for musculoskeletal ailments is growing. WBC, involving brief exposure to extremely low temperatures, is increasingly used for its analgesic, anti-inflammatory, and antioxidant effects. The paper examines the physiological impacts of WBC on cardiovascular, musculoskeletal, hematologic, hormonal, and metabolic systems. Specific orthopaedic applications discussed include its role in the management of fractures, osteoarthritis, osteonecrosis of the femoral head, osteomyelitis, adhesive capsulitis, tendinopathies, rheumatic pathologies, chronic pain syndromes, and fibromyalgia. The study also highlights the benefits and drawbacks of WBC, including its potential to improve athletic performance, recovery, mood, and well-being, while noting risks like frostbite and impaired muscle strength. Clinical evidence from various studies is evaluated, revealing a spectrum of outcomes. For instance, WBC shows promise in enhancing bone health in athletes and providing relief in osteoarthritis and fibromyalgia patients. However, evidence for its efficacy in conditions like chronic pain syndromes and osteomyelitis is less robust. The paper underscores the need for further research to establish standardised protocols and understand long-term effects. While WBC offers significant benefits in orthopaedics, understanding its limitations and potential risks is crucial for its safe and effective clinical application.

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.

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.

The New Consumer Protection Act Controversy: Does It Apply to Doctors in India?

A new Consumer Protection Act (CPA) was introduced in 2019 and has created quite a stir in the medical fraternity. There is widespread uncertainty as to whether this new Act applies to the medical profession. However, on careful review of the original CPA of 1986, the definition of services included within the Act, and understanding the changes introduced in CPA 2019, the legal application of CPA 2019 to medical professionals becomes clear. While the term medical services has been removed from the list of services under the purview of the Act, the phrase "but not limited to" before listing the services leaves the door open for the inclusion of other services.

Advancements in Tuberculosis Diagnostics: A Comprehensive Review of the Critical Role and Future Prospects of Xpert MTB/RIF Ultra Technology.

Tuberculosis remains a persistent global health challenge, demanding swift and accurate diagnostic methods for effective treatment. The emergence of the Xpert MTB/RIF Ultra system marks a significant milestone in combating tuberculosis, streamlining the identification of Mycobacterium tuberculosis, and advancing our pursuit of eradicating the disease. Delving into the therapeutic landscape of tuberculosis and rifampicin resistance, this scientific narrative review offers a comprehensive exploration. It begins by delving into the historical backdrop and the hurdles encountered with traditional tuberculosis diagnostics. From there, it traces the journey of the Xpert MTB/RIF technology, underscoring its molecular underpinnings. In this narrative review, the performance of the Xpert MTB/RIF Ultra system undergoes thorough scrutiny, encompassing investigations into sensitivity, specificity, and comparisons with alternative diagnostic methods. The spotlight shines on its clinical applications across diverse scenarios, from diagnosing pulmonary and extrapulmonary tuberculosis to its pivotal role in identifying rifampicin resistance. The study also evaluates its clinical efficacy in enhancing patient outcomes and supporting global tuberculosis control initiatives. However, the review does not shy away from discussing the challenges and limitations associated with the Xpert MTB/RIF Ultra system. It meticulously addresses concerns regarding cost, infrastructure requirements, and potential diagnostic inaccuracies. Offering a panoramic view, the review assesses the system's impact in resource-constrained settings and its potential to bolster tuberculosis elimination endeavors worldwide. Peering into the future, it explores ongoing research avenues and potential enhancements in Xpert MTB/RIF Ultra technology, envisioning a landscape of improved performance, broader applications, and emerging diagnostic innovations in the realm of tuberculosis diagnostics.

Tuberculosis of the Femur With Intramedullary Abscesses and No Pulmonary Foci in an Immunocompetent Male: A Rare Case.

Tuberculosis of the long bones/femur, especially in an immunocompetent person, is a challenging diagnosis. It is a rare entity, even in endemic settings. The non-specific clinical features, backed by a low suspicion about such presentations even in endemic settings, may result in delayed diagnosis and often unfavorable treatment outcomes. The situation becomes even more challenging in the absence of pulmonary foci and a contact history of tuberculosis. Here is a case of a young adult male who presented with complaints of pain over his left leg for three months. A diagnosis was achieved with magnetic resonance imaging and the isolation of the bacteria from a bone biopsy using a cartridge-based nucleic acid amplification test. Antituberculous treatment was promptly initiated.

Tuberculosis of the Parietal Bone in an Indian Boy: A Rare Entity.

Tuberculosis is a common issue in endemic regions. The disease can affect both adults and children. Tuberculosis involving the flat bones of the skull is infrequently reported. Besides, reports of parietal bone tuberculosis in children are rare and a diagnostic challenge. Often, these cases report late, and this could compromise the treatment outcomes. Herein, a case of post-traumatic tuberculosis of the left parietal bone is presented in a child. The diagnosis was achieved by radiometric investigations and the isolation of Mycobacterium tuberculosis from the pus. He was initiated on antituberculous chemotherapy.

Spina Ventosa of the Thumb With Valgus Deformity in a Female With No Pulmonary Involvement: A First Report of Its Type in an Immunocompetent Adult From India.

Small bone involvement caused by Mycobacterium tuberculosis infection is an uncommon clinical entity. Usually, the condition is linked to the spread of bacteria from the lungs. It is rather uncommon for people without pulmonary seeding, trauma, or a history of tuberculosis to experience isolated episodes of spina ventosa. We describe a rare case of an immunocompetent Indian woman, aged 25, who complained of swelling in her left thumb. The diagnosis of primary tubercular dactylitis of the thumb was made after a thorough clinical and laboratory workup, and she received conservative treatment.

Surgical Preparedness Index in Orthopaedics During the Coronavirus Disease 2019 (COVID-19) Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has increased the vulnerability of routine surgical procedures and elective surgery preparedness all over the world, with the suspension of most elective surgeries during the pandemic and the backlog of patients currently on waiting lists, especially in publicly funded healthcare systems. On average, at the beginning of the year 2022, about 200 million patients awaited surgery all over the world. By enhancing the strength of surgical preparedness, there is a better chance of strengthening elective surgical systems against shocks such as future pandemics or climate emergencies. We explore the implications, challenges, and strategies of the concept of surgical preparedness to maintain sustainability in the global healthcare system, especially in low- and middle-income countries (LMICs), with the experiences gained during the COVID-19 pandemic.

Beyond Blame: Is India Ready for No-Fault Liability in Healthcare?

In contemporary healthcare systems, the pursuit of justice intertwines with fault attribution and liability determination. The exploration of no-fault liability as a potential alternative within India's healthcare landscape delves into its feasibility and implications. Drawing from international experiences, regulatory frameworks, and societal readiness, the complexities and potential benefits of adopting a no-fault liability system are elucidated. Perspectives from patients, healthcare providers, and broader societal stakeholders are considered, highlighting both the advantages and challenges associated with such a transition. Addressing disparities in access, legal reforms, and logistical hurdles underscores the groundwork necessary for potential adoption, signaling a potential paradigm shift toward equitable compensation and accountability within India's healthcare system.

Customizable Hyperextension Splint for Mallet Finger.

Introduction: Mallet finger is a common deformity occurring due to the traumatic detachment of the extensor tendon at its insertion in the distal phalanx. Despite several different methods of splinting being available, residual extensor lag remains one of the most common complications of conservative treatment. Technique Report: We demonstrate a novel technique to make a hyperextension splint which can be customized as per the individual. The pictorial demonstration depicts every step in the preparation, application, and maintenance of the splint. Conclusion: We believe that the use of such easily accessible materials and visual demonstration of each step, with pointers along the way to verify the correct technique, will empower any medical professional, to satisfactorily treat such injuries at the primary point of contact, without necessitating the services of a hand surgeon.

GOLD-Induced Cytokine (GOLDIC): A Critical Review of Its Properties, Synthesis, and Biomedical Applications.

This narrative review examines the intricate landscape of gold-induced cytokine responses, delving into the anti-inflammatory and immune-modulating properties of gold compounds, with a primary focus on their application in treating rheumatoid arthritis and other autoimmune conditions. Utilizing a comprehensive search strategy across major scientific databases, we identified and analyzed a diverse range of studies published within the last two decades. The aim of this review is to provide a nuanced understanding of the current state of knowledge, addressing key questions regarding the mechanisms by which gold compounds modulate cytokine responses and their clinical implications. Our review encompasses an in-depth exploration of the anti-inflammatory effects of gold compounds, emphasizing their impact on pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). Moreover, we investigate the lesser-explored terrain of immune modulation, shedding light on the ability of gold compounds to influence anti-inflammatory cytokines, notably interleukin 10 (IL-10). Through an extensive analysis of the literature, we unravel the multifaceted mechanisms underlying gold-induced cytokine responses, including the inhibition of nuclear factor kappa B (NF-κB) signaling and interference with janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. In exploring the clinical applications of gold-induced cytokine modulation, we synthesize findings from relevant studies, elucidating the potential of gold compounds as therapeutic agents. However, challenges such as variability in formulations and diverse cytokine assessment methods are discussed, emphasizing the need for standardization in both research and clinical settings. Looking ahead, our scoping review identifies key unanswered questions and proposes future directions for research in this domain. We discuss emerging therapeutic strategies, considering the integration of gold compounds with other modalities to optimize treatment outcomes. This comprehensive review serves as a foundational resource for researchers, clinicians, and policymakers seeking a nuanced understanding of gold-induced cytokine responses, paving the way for further advancements in this critical area of study.

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.

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.