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Abstract Regarding medico-legal malpractice suits, lawyers and insurers focus on informed consent documentation. Unfortunately, there is no standard protocol for obtaining informed consent for platelet-rich plasma (PRP) injections. The objective of the present study was to create a pre-designed, evidence-based informed consent form specifically for PRP injections. The current evidence on the medico-legal implications of PRP injections was accessed, as well as informed consent in general and specifically informed consent in PRP injections. Additionally, we interviewed orthopaedic surgeons and patients who had undergone PRP injections in the past year using a semi-structured approach. A legally valid and evidence-based informed consent form for PRP injections ensures rights, encouraging open communication and transparency between the patient and surgeon. Moreover, if a lawsuit arose, informed consent would be a critical document in surgeons' defence and would withstand scrutiny from lawyers and the judiciary. An evidence-based informed consent form for PRP injections was elaborated and reviewed by a legal expert to ensure adherence to legal proprieties. The final form of the informed consent for PRP injection was administered for one year and validated at our institution.

Abstract Musculoskeletal disorders encompass a wide range of conditions that impact the bones, joints, muscles, and connective tissues within the body. Despite the ongoing debate on toxicity and administration, ozone demonstrated promise in managing several musculoskeletal disorders, modulating pain and inflammation. A literature search was conducted. The research design, methods, findings, and conclusions of the studies were then examined to evaluate the physiological effects, clinical application, controversies, and safety of the application of ozone in musculoskeletal medicine. Ozone application demonstrates considerable therapeutic applications in the management of musculoskeletal disorders, including fractures, osteoarthritis, and chronic pain syndromes. Despite these advantages, studies have raised concerns regarding its potential toxicity and emphasized the importance of adhering to stringent administration protocols to ensure safety. Additionally, heterogeneities in patient reactions and hazards from oxidizing agents were observed. Given its anti-inflammatory and analgesic qualities, ozone therapy holds potential in the management of several musculoskeletal disorders. Additional high-quality research with long follow-up is required to refine indications, efficacy and safety profile. Finally, for wider clinical acceptability and utilization, the development of international recommendations is essential.

Abstract Introduction Informed consent documentation is often the first area of interest for lawyers and insurers when a medico-legal malpractice suit is concerned. However, there is a lack of uniformity and standard procedure about obtaining informed consent for total knee arthroplasty (TKA). We developed a solution for this need for a pre-designed, evidence-based informed consent form for patients undergoing TKA. Materials and methods We extensively reviewed the literature on the medico-legal aspects of TKA, medico-legal aspects of informed consent, and medico-legal aspects of informed consent in TKA. We then conducted semi-structured interviews with orthopaedic surgeons and patients who had undergone TKA in the previous year. Based on all of the above, we developed an evidence-based informed consent form. The form was then reviewed by a legal expert, and the final version was used for 1 year in actual TKA patients operated at our institution. Results Legally sound, evidence-based Informed Consent Form for Total Knee Arthroplasty. Conclusion The use of legally sound, evidence-based informed consent for total knee arthroplasty would be beneficial to orthopaedic surgeons and patients alike. It would uphold the rights of the patient, promote open discussion and transparency. In the event of a lawsuit, it would be a vital document in the defence of the surgeon and withstand the scrutiny of lawyers and the judiciary.

Introduction: The myriad presentation of osteoarticular brucellosis make the patient seek the help of general practitioners, orthopaedic and rheumatology specialists. Moreover, the lack of disease-specific symptomatology is the leading cause of the delay in diagnosing osteoarticular brucellosis. Given the increasing number of spinal brucellosis cases across the country, no literature is presented on the systematic management of spinal brucellosis. However, with our experience, we formulated a classification for managing spinal brucellosis. Methods: A single-centred prospective observational study was conducted with 25 confirmed cases of spinal brucellosis. Patients were analysed and graded clinically, serologically, and radiologically and were managed with antibiotics for 10–12 weeks, and if necessary, stabilisation and fusion were done based on the treatment classification devised. All patients were followed up to ensure disease clearance at serial follow-up with relevant investigations. Results: The mean age of the study participants was 52.16 ± 12.53 years. According to spondylodiscitis severity code (SSC) grading, four patients belong to grades 1, 12 to grade 2 and 9 to grade 3 at presentation. Erythrocyte sedimentation rate (p = 0.02), c-reactive protein (p

Globally, neurological diseases pose a major burden to healthcare professionals in terms of the management and prevention of the disorder. Among neurological diseases, Alzheimer’s disease (AD) accounts for 50%–70% of dementia and is the fifth leading cause of mortality worldwide. AD is a progressive, degenerative neurological disease, with the loss of neurons and synapses in the cerebral cortex and subcortical regions. The management of AD remains a debate among physicians as no standard and specific “disease-modifying” modality is available. The concept of ‘Regenerative Medicine’ is aimed at regenerating the degenerated neural tissues to reverse the pathology in AD. Genetically modified engineered stem cells modify the course of AD after transplantation into the brain. Extracellular vesicles (EVs) are an emerging new approach in cell communication that involves the transfer of cellular materials from parental cells to recipient cells, resulting in changes at the molecular and signaling levels in the recipient cells. EVs are a type of vesicle that can be transported between cells. Many have proposed that EVs produced from mesenchymal stem cells (MSCs) may have therapeutic promise in the treatment of AD. The biology of AD, as well as the potential applications of stem cells and their derived EVs-based therapy, were explored in this paper.

Abstract Introduction The etiology of ischiofemoral impingement (IFI) syndrome, an unusual and uncommon form of hip pain, remains uncertain. Some patients demonstrate narrowing of the space between the ischial tuberosity and lesser trochanter from trauma or abnormal morphology of the quadratus femoris muscle. Combined clinical and imaging aid in the diagnosis. Case report A 32-year-old female presented with a 3 years history of pain over the lower aspect of the right buttock, aggravated by movements of the right hip, and partially relieved with rest and medications. The right hip showed extreme restriction of abduction and external rotation. MRI of the right hip showed reduced ischiofemoral space and quadratus femoris space when compared to the left hip. The patient underwent endoscopic resection of the right lesser trochanter, with no recurrence of pain at 2 years. Conclusion An unusual cause of hip pain, IFI syndrome, should be suspected when hip pain at extremes of movement is associated with signal abnormality of quadratus femoris muscle. Management is tailored to address the inciting factors that precipitated the IFI syndrome.

Introduction: Rhabdomyosarcoma (RMS) is a soft tissue tumor arising from myogenic precursor cells. RMS involving the spine primarily is rare, with only few such reported cases. Clinical image report: A 43 year old gentleman had complains of low back pain, weakness of lower limbs and urinary incontinence for three months. With radiological and histopathological investigations, the patient was diagnosed as alveolar type of RMS. Conclusion: Identifying the histological type of RMS pave a way for the treatment plan and to prognosticate the disease activity.

Drugs are currently not licensed in specific to pulverize COVID-19. On an emergency basis, vaccines were approved to prevent the further spread of COVID-19. This serves as a potential background for considering the optimization of biologics. In this context, evidence on convalescent plasma and stem cells has shown a beneficial role. Here, we have considered this as plausible therapy, and further hypothesize that their cocktails will synergistically boost the immunogenicity to relegate COVID-19. This warrants a large volume clinical trial on an emergent basis, because the sooner we establish a safe and effective cure, the better.

Introduction: Several sociodemographic variables, including ethnic inequality, have been identified as potentially influencing the uptake of COVID-19 vaccinations. To develop herd immunity against COVID-19, at least 70–85% of the population must be vaccinated. As the situation with COVID-19 changes, the public's perception keeps fluctuating. We designed a survey to determine the prevalence of vaccinated individuals and the rate of infectivity post-vaccination. We also aimed to study the clinical manifestations and infectivity of the SARS-CoV-2 virus post-vaccination. Materials and methods: A cross-sectional study was conducted from May 10, 2021 to July 10, 2021 across India through a pre-tested validated semi-structured self-administered electronic questionnaire, to the study subjects with objectives explained and the confidentiality of the data and results had been assured. The questionnaires were prepared using Google forms and the link was sent across social media platforms such as WhatsApp, Facebook, and various social platforms where people are actively engaged following the restrictions and protocols of social distancing. General demographic data, followed by their lifestyle and comorbid conditions, and data on their vaccination, infectivity, and side effects were collected. Results: We included 2334 participants in the study, of which the majority of the study participants were in the age group of 25–34 years (38.6%). 1729 were vaccinated individuals of which 80.7% had received Covishield and 17.8% had received Covaxin. Around 61.1% have received both doses among 1729 vaccinated individuals and 38.9% had received only one dose of vaccine. The majority of the fully vaccinated individuals had a gap of 4–5 weeks for the second dose (37.1%) followed by 5–6 weeks (11.2%). Post-vaccination 50.8% had experienced muscle pain, 46% had experienced fatigue, 36.5% weakness, and 12.3% back pain. Among vaccinated 26% turned out to be COVID-19 positive and 44.5% non-vaccinated got infected. The odds of infection among non -vaccinated individuals was 2.27 times higher than vaccinated individuals. Individuals who encountered the viral antigen for the second time experienced either through vaccination or infection demonstrated exaggerated inflammatory response which is explained by the antibody-dependent enhancement phenomenon without life-threatening complications. Conclusion: Although more than 50% of the vaccinated individuals experienced some form of musculoskeletal side effects, we noted a high acceptance rate (74%) of vaccination among the participants. The vaccinated individuals were two times safer from infection compared to the non-vaccinated individuals.

Corticosteroids (CS) have been used in the management regimens for COVID-19 disease to mitigate the cytokine storm and ill effects of the pulmonary inflammatory cascade. With the rampant use of CS, clinicians started reporting the occurrence of osteonecrosis of the femoral head (OFH). In this systematic review, we aim to analyze the literature and identify the definitive cumulative dose and duration of CS needed for the development of OFH based on the SARS model and generate a risk-based screening recommendation for OFH in convalescent COVID-19 patients to facilitate early identification and management. An electronic database search was conducted until December 2022 in PubMed, Web of Science, Embase, and CNKI (China Knowledge Resource Integrated Database). Studies involving CS therapy and osteonecrosis data in SARS patients were included. Three authors independently extracted the data from the included studies and a dose–response meta-analysis was performed for various doses and duration of CS utilized in the included studies. We selected 12 articles with 1728 patients in the analysis. The mean age was 33.41 (±4.93) years. The mean dosage of CS administered was 4.64 (±4.7) g which was administered for a mean duration of 29.91 (±12.3) days. The risk of osteonecrosis increases at pooled OR of 1.16 (95% CI 1.09–1.23, p < 0.001) per 2.0 g increase in the cumulative dose of CS usage. Similarly, the risk increases at pooled OR of 1.02 (95% CI 1.01–1.03, p < 0.001) per 5 days of increase in the cumulative duration of CS usage. A cumulative dosage of 4 g and a duration of 15 days were determined as the critical cut-off for the non-linear dose–response relationship observed. Appropriate and frequent screening of these individuals at regular intervals would help in the identification of the disease at an early stage in order to treat them appropriately.

Over the past few decades, various forms of platelet concentrates have evolved with significant clinical utility. The newer generation products, including leukocyte-platelet-rich fibrin (L-PRF) and advanced platelet-rich fibrin (A-PRF), have shown superior biological properties in musculoskeletal regeneration than the first-generation concentrates, such as platelet-rich plasma (PRP) and plasma rich in growth factors. These newer platelet concentrates have a complete matrix of physiological fibrin that acts as a scaffold with a three-dimensional (3D) architecture. Further, it facilitates intercellular signaling and migration, thereby promoting angiogenic, chondrogenic, and osteogenic activities. A-PRF with higher leukocyte inclusion possesses antimicrobial activity than the first generations. Due to the presence of enormous amounts of growth factors and anti-inflammatory cytokines that are released, A-PRF has the potential to replicate the various physiological and immunological factors of wound healing. In addition, there are more neutrophils, monocytes, and macrophages, all of which secrete essential chemotactic molecules. As a result, both L-PRF and A-PRF are used in the management of musculoskeletal conditions, such as chondral injuries, tendinopathies, tissue regeneration, and other sports-related injuries. In addition to this, its applications have been expanded to include the fields of reconstructive cosmetic surgery, wound healing in diabetic patients, and maxillofacial surgeries.

Adhesive capsulitis shoulder is a common problem of patients presenting with shoulder pain and disability. The approach to such patients includes a variety of modalities. This systematic review evaluates the efficacy of intra-articular injections of platelet-rich plasma (PRP) in the treatment. A literature search was performed between January 2010 and 30 May 2022. MeSH terms used were ‘Platelet-rich plasma’ OR ‘PRP’ AND ‘Frozen shoulder’ OR ‘Adhesive capsulitis shoulder’ OR ‘Periarthritis shoulder’. The search included published articles in the English language involving human subjects. Studies evaluating other types of shoulder disorders, in vitro studies, review articles, animal-model studies, and pre-clinical trials were excluded. The data regarding study characteristics, efficacy, and safety outcomes were analyzed. A total of 11 studies with 347 patients over 10 years were finally included in this review. Most publications were in 2019 and 2020, mostly from India. This review included seven comparative studies, three case series, and one case report. In seven studies, a single intra-articular PRP injection was administered, whereas in the rest of the studies two or multiple injections were given. Only one study demonstrated an equivocal efficacy of PRP and steroid intra-articular injection. The rest all depicted better clinical and functional outcomes with the PRP injection. Only one study compared the outcomes of hydro-dissection treatment in adhesive capsulitis with the intra-articular PRP injection. The rest all either examined PRP alone or compared it with the steroid intra-articular injection. None of the studies showed any major side effects. The intra-articular injections of PRP in the management of adhesive capsulitis of the shoulder provide a new treatment approach. Further studies are required to ascertain the efficacy and safety of the PRP intraarticular injection as a management alternative in adhesive capsulitis.

The well-orchestrated process of wound healing may be negatively impacted from interrupted or incomplete tissue regenerative processes. The healing potential is further compromised in patients with diabetes mellitus, chronic venous insufficiency, critical limb ischemia, and immunocompromised conditions, with a high health care burden and expenditure. Stem cell-based therapy has shown promising results in clinical studies. Mesenchymal stem cell-derived exosomes (MSC Exos) may favorably impact intercellular signaling and immunomodulation, promoting neoangiogenesis, collagen synthesis, and neoepithelization. This article gives an outline of the biogenesis and mechanism of extracellular vesicles (EVs), particularly exosomes, in the process of tissue regeneration and discusses the use of preconditioned exosomes, platelet-rich plasma-derived exosomes, and engineered exosomes in three-dimensional bioscaffolds such as hydrogels (collagen and chitosan) to prolong the contact time of exosomes at the recipient site within the target tissue. An appropriate antibiotic therapy based on culture-specific guidance coupled with the knowledge of biopolymers helps to fabricate nanotherapeutic materials loaded with MSC Exos to effectively deliver drugs locally and promote novel approaches for the management of chronic wounds.

The virus causing monkeypox, a rare zoonotic viral disease, belongs to the Poxviridae family and the Orthopoxvirus genus. On 23 July 2022, the World Health Organization (WHO) declared the monkeypox outbreak as a Public Health Emergency of International Concern (PHEIC). From May to July 2022, a multi-country outbreak of monkeypox was reported in both endemic and non-endemic regions. Major goals of managing monkeypox are to identify the suspected cases, detect generic orthopoxvirus DNA at a state or commercial laboratory, and establish the Centers for Disease Control and Prevention real-time polymerase chain reaction testing. Currently, there are no approved treatments for monkeypox virus infection. However, a variety of antiviral medications originally designed for the treatment of smallpox and other viral infections could be considered. Pre-exposure prophylaxis for laboratory and health care employees and post-exposure prophylaxis for individuals with high-risk or intermediate-risk exposures are to be considered. The CDC Emergency Operations Center is available for advice on the appropriate use of medical countermeasures, and can help in obtaining antiviral drugs and vaccines from the National Strategic Stockpile. This review gives an overview of the global scenario, clinical presentation, and management of monkeypox in the light of a global public health emergency.

This study investigates the role of Sygen® in diabetic peripheral neuropathy, a severe disease that affects the peripheral nervous system in diabetic individuals. This disorder often impacts the lower limbs, causing significant discomfort and, if left untreated, progresses into more serious conditions involving chronic ulcers and even amputation in many cases. Although there are management strategies available, peripheral neuropathies are difficult to treat as they often present multiple causes, especially due to metabolic dysfunction in diabetic individuals. Gangliosides, however, have long been studied and appreciated for their role in neurological diseases. The monosialotetrahexosylganglioside (GM1) ganglioside, popularly known as Sygen, provides beneficial effects such as enhanced neuritic sprouting, neurotrophism, neuroprotection, anti-apoptosis, and anti-excitotoxic activity, being particularly useful in the treatment of neurological complications that arise from diabetes. This product mimics the roles displayed by neurotrophins, improving neuronal function and immunomodulation by attenuating exacerbated inflammation in neurons. Furthermore, Sygen assists in axonal stabilization and keeps nodal and paranodal regions of myelin fibers organized. This maintains an adequate propagation of action potentials and restores standard peripheral nerve function. Given the multifactorial nature of this complicated disorder, medical practitioners must carefully screen the patient to avoid confusion and misdiagnosis. There are several studies analyzing the role of Sygen in neurological disorders. However, the medical literature still needs more robust investigations such as randomized clinical trials regarding the administration of this compound for diabetic peripheral neuropathies, specifically.

Tissue engineering and regenerative medicine (TERM) have paved a way for treating musculoskeletal diseases in a minimally invasive manner. The regenerative medicine cocktail involves the usage of mesenchymal stem/stromal cells (MSCs), either uncultured or culture-expanded cells along with growth factors, cytokines, exosomes, and secretomes to provide a better regenerative milieu in degenerative diseases. The successful regeneration of cartilage depends on the selection of the appropriate source of MSCs, the quality, quantity, and frequency of MSCs to be injected, and the selection of the patient at an appropriate stage of the disease. However, confirmation on the most favorable source of MSCs remains uncertain to clinicians. The lack of knowledge in the current cellular treatment is uncertain in terms of how beneficial MSCs are in the long-term or short-term (resolution of pain) and improved quality of life. Whether MSCs treatments have any superiority, exists due to sources of MSCs utilized in their potential to objectively regenerate the cartilage at the target area. Many questions on source and condition remain unanswered. Hence, in this review, we discuss the lineage differentiation potentials of various sources of MSCs used in the management of knee osteoarthritis and emphasize the role of tissue engineering in cartilage regeneration.

Stem cells can be defined as the cells that have the capacity to both self-renew and give rise to differentiated cells. Under the right conditions and signals, depending on their origin and bio-plasticity, stem cells can differentiate into multiple cell lineages and develop into various mature cells. Stem cell therapy is a fast-developing branch of medicine that includes the most innovative regenerative therapies for the restoration of cell and tissue function in individuals with severe diseases. Stem cell research has resulted in the emergence of cell-based therapies for disorders that are resistant to conventional drugs and therapies, and they are considered under the category of an Advanced Therapeutic Medicinal Product (ATMP). The FDA and the European Medicines Agency (EMA) devised a new strategy in 2017 with the aim of unifying the standards for development of ATMPs such that it is easy to exchange information at the international level. In this review, we discuss the evolution of mesenchymal stem cell-based therapy as an ATMP in the global and Indian scenarios, along with the guidelines governing their usage and clinical application of these therapeutics.

Human bone marrow (BM) has been highlighted as a promising source of mesenchymal stromal cells (MSCs) containing various growth factors and cytokines that can be potentially utilized in regenerative procedures involving cartilage and bone. However, the proportion of MSCs in the nucleated cell population of BM is only around 0.001% to 0.01% thereby making the harvesting and processing technique crucial for obtaining optimal results upon its use in various regenerative processes. Although several studies in the literature have given encouraging results on the utility of BM aspiration concentrate (BMAC) in various regenerative procedures, there is a lack of consensus concerning the harvesting variables such as choice of anesthetic agent to be used, site of harvest, size of the syringe to be used, anticoagulant of choice, and processing variables such as centrifugation time, and speed. In this review article, we aim to discuss the variables in the harvesting and processing technique of BMAC and their impact on the yield of MSCs in the final concentrate obtained from them.

Study Design: Meta-analysis. Objectives: We aimed to analyze the impact of cultured expansion of autologous 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 until August 2021 for RCTs analyzing the efficacy and safety of culture-expanded compared to non-cultured autologous MSCs in the management of knee osteoarthritis. The Visual Analog Score (VAS) for pain, Western Ontario McMaster University’s Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the analyzed outcomes. Analysis was performed in R-platform using OpenMeta [Analyst] software. Results: Overall, 17 studies involving 767 patients were included for analysis. None of the studies made a direct comparison of the culture expanded and non-cultured MSCs, hence we pooled the results of all the included studies of non-cultured and cultured types of MSC sources and made a comparative analysis of the outcomes. At six months, culture expanded MSCs showed significantly better improvement (p < 0.001) in VAS outcome. Uncultured MSCs, on the other hand, demonstrated significant VAS improvement in the long term (12 months) in VAS (p < 0.001), WOMAC (p = 0.025), KOOS score (p = 0.016) where cultured-expanded MSCs failed to demonstrate a significant change. Culturing of MSCs did not significantly increase the complications noted (p = 0.485). On sub-group analysis, adipose-derived uncultured MSCs outperformed culture-expanded MSCs at both short term (six months) and long term (12 months) in functional outcome parameters such as WOMAC (p < 0.001, p = 0.025), Lysholm (p < 0.006), and KOOS (p < 0.003) scores, respectively, compared to their controls. Conclusions: We identified a void in literature evaluating the impact of culture expansion of MSCs for use in knee osteoarthritis. Our indirect analysis of literature showed that culture expansion of autologous MSCs is not a necessary factor to obtain superior results in the management of knee osteoarthritis. Moreover, while using uncultured autologous MSCs, we recommend MSCs of adipose origin to obtain superior functional outcomes. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the need for culture expansion of MSCs for use in cellular therapy of knee osteoarthritis.

The periosteum, with its outer fibrous and inner cambium layer, lies in a dynamic environment with a niche of pluripotent stem cells for their reparative needs. The inner cambium layer is rich in mesenchymal progenitors, osteogenic progenitors, osteoblasts, and fibroblasts in a scant collagen matrix environment. Their role in union and remodeling of fracture is well known. However, the periosteum as a source of mesenchymal stem cells has not been explored in detail. Moreover, with the continuous expansion of techniques, newer insights have been acquired into the roles and regulation of these periosteal cells. From a therapeutic standpoint, the periosteum as a source of tissue engineering has gained much attraction. Apart from its role in bone repair, analysis of the bone-forming potential of periosteum-derived stem cells is lacking. Hence, this article elucidates the role of the periosteum as a potential source of mesenchymal stem cells along with their capacity for osteogenic and chondrogenic differentiation for therapeutic application in the future.

Stem cell therapy has been considered a promising strategy in the management of both type I and type II diabetes mellitus (DM) because of its immunomodulatory and regenerative capability to restore the beta cell number and function. Various modalities of cellular therapy like transplantation of pancreatic islet cells, transplantation of pancreatic ductal stem cells, and mesenchymal stromal cell transplantation have been tried, and the modality is undergoing rapid advancements that may become the reality in the near future. In the course of its evolution, it is essential to have a comprehensive summary of the progress for a greater capacity to refine our future directives. With technological developments like data mining, graphic drawing, and information analytics combined with computational statistics, visualization of scientific metrology has become a reality. With a newer perspective, we intend to use scientometric tools including text mining, co-word analysis, word frequency analysis, co-citation analysis, cluster network analysis, to perform a systematic and comprehensive analysis of the research trend in stem cell therapy in the management of DM over the past three decades (1990–2020) and to identify the future research hotspots.