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Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disorder involving joint pathogenesis, cartilage and bone deformities, along with systemic comorbidities, affecting over 75 million people worldwide. At present there is no cure for RA and the current treatment modalities utilized have limitations and side effects. Over the last decades, mesenchymal stem/stromal cells (MSCs), both autologous and allogenic, have emerged as potential safe and effective alternatives. In this review, we highlighted the safety and efficacy of both autologous as well as allogenic MSCs to treat RA based on recently published clinical studies. These studies demonstrated that use of autologous or allogenic MSCs is safe and laid the foundation for multi-center prospective open label non-randomized trials and double blinded randomized controlled trials with larger sample size to further establish the safety and efficacy of these MSCs to alleviate symptoms of RA, thereby, ultimately justifying their clinical use.

Knee osteo-arthritis increases the global burden and adds morbidity to the patient. Total knee replacement is on the rise with patients presenting at stage of advanced knee arthritis increasing surgical morbidity on the patient. Knee cartigram, helps to diagnose early cartilage damage with normal knee radiographs. Addressing cartilage loss at an early stage can preserve the innate knee delaying the onset of arthritis and prevent knee replacement.

Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune ailment which involves joint pathogenesis, bone and cartilage irregularities, together with systemic comorbidities, impacting over 75 million people worldwide. At present there is no remedy for RA and the existing treatment modalities utilized have shortcomings and side effects. Recently, there has been an increased interest in use of biologics, such as platelet-rich plasma (PRP), for regenerative medicine applications, including for musculoskeletal ailments. This prompted consideration of use of PRP in patients suffering with RA. In this editorial, we highlighted the safety and efficacy of PRP to treat RA based on recently published clinical studies. These studies, despite preliminary, demonstrated that use of PRP is safe and laid the foundation for multi-center prospective open-label non-randomized trials and double-blinded randomized controlled trials with larger sample size to further evaluate the efficacy of PRP to alleviate symptoms of RA for potential clinical usage.

Meta-analysisOur objective is to review the randomized controlled trials (RCTs) that have been conducted previously on the topic of osteoarthritis of the knee to assess and compare the efficacy and safety of autologous and allogeneic sources of mesenchymal stromal cells (MSCs) in the treatment of osteoarthritis.We searched the electronic databases PubMed, Embase, Web of Science, and the Cochrane Library until August 2021 for randomised controlled trials (RCTs) analysing the efficacy and safety of autologous and allogeneic sources of MSCs in the management of knee osteoarthritis. These searches were conducted independently and in duplicate. The outcomes that were taken into consideration for analysis were the visual analogue score (VAS) for pain, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), the Lysholm score, and adverse events. The OpenMeta [Analyst] software was utilised to carry out the analysis in the R platform.In total, 21 studies with a total of 936 patients were considered for this analysis. Because none of the studies made a direct comparison of the autologous and allogeneic sources of MSCs, we pooled the results of all of the included studies of both sources and made a comparative analysis of how the two types of MSCs fared in their respective applications. Although both allogeneic and autologous sources of MSCs demonstrated significantly better VAS improvement after 6 months (Our analysis of literature showed that autologous sources of MSCs stand superior to allogeneic sources of MSC with regard to their consistent efficacy for pain, functional outcomes, and safety. However, we strongly recommend that further studies be conducted that are of a high enough quality to validate our findings and reach a consensus on the best source of MSCs for use in cellular therapy treatments for knee osteoarthritis.The online version contains supplementary material available at 10.1007/s43465-022-00751-z.

Biofilm producers pose a major challenge in treating implant-related orthopedic infections (IROIs). The incidence of IROIs for the closed fracture amounts to 1% to 2% whereas for open fracture it is up to 30%. Due to inappropriate and irrational use of antibiotics in the management of infections, there is an emergence of a global "antimicrobial resistance crisis". To combat these antimicrobial resistance crises, a few innovative and targeted therapies like nanomedicine, phage therapy, antimicrobial peptides, and sonic therapies have been introduced. In this review, we have detailed the basic mechanisms involved in the employment of bacteriophage therapy for IROIs, along with the preclinical and clinical data on its utility. We also present the guidelines on its regulation, processing, and limitations of bacteriophage therpay to combat the upcoming era of antibiotic resistance.

13 Biennial International Congress of Orthopaedic Rheumatology (ICOR), wasorganized for the first time in ‘City of Joy’ by Indian Orthopaedic Rheumatology Association (IORA) under the aegis of WBOA in association with ESI-PGIMSR, ESIC Medical College, Joka Kolkata from 17 – 19 June 2022. The main Conference was organized from 18 – 19 June 2022 in Bishwa Bangla Convention Centre (The biggest convention Centre of India). Apart from the main conference, there were 8 Preconference workshops, conducted in two Premier Medical Institutions of Kolkata on different topics on 17 June 2022. Hallmark of entire Conference was lively interactive discussions amongst delegates. Academic Report Update of Pre-conference workshops & Main conference are highlighted in this Short Communication.

Mesenchymal stem cells, because of their ability to differentiate along variable cell lineages and renew themselves is a topic of interest in orthopedics for their potential role in avascular necrosis of femoral head, osteoarthritis, intervertebral disc disease, ligamentous and meniscal injuries, inducing growth in osteogenesis imperfecta and gene therapy. They also possess immunosuppressive and immunomodulatory properties. Mesenchymal stem cells can be procured from different tissue sources, such as umbilical cord, synovial tissue, breast milk, menstrual blood, adipose tissue, bone marrow, dentine pulp etc. In this review, we have attempted to make a study of the recent advances in emerging new sources of mesenchymal stem cells and their therapeutic potentials.

We are reporting a rare case of a painful accessory ossification center of the bilateral medial malleoli in a 9 years old girl. Patient was not involved in any sport activity. There was no local foot deformity and limb malalignment. The patient was treated conservatively. There was complete clinical and radiographic healing of the medial malleolus eight months after the first presentation. Osteochondrosis of the accessory ossification center of medial malleolus is generally unilateral and bilateral involvement is very rare. There are various differential diagnosis for this pathological condition with similar clinical features and presentation in this age group. We ruled out the uncommon pathological conditions causing chronic pain in the medial malleolus during this period of skeletal growth. We consider this painful condition to be classified as a bilateral osteochondroses of the accessory ossification center of the medial malleolus. Osteochondrosis of the accessory ossification center of the bilateral medial malleolus is a rare entity. Due to rarity of disease and common presentation similar to other disease this is commonly misdiagnosed or missed in clinical practice. Osteochondrosis is characterized by a disturbance of endochondral ossification in skeletally immature patients and should be investigated in children having a history of persistent foot and ankle pain. An increased clinical attention to this painful condition could lead to improved diagnosis and treatment among the paediatric age group.

Recent developments in cellular and molecular biology have emerged as a potent tool in the management of orthopaedic illnesses and injuries. Upon binding to the target cell receptor, the growth factor from platelets triggers the activation of an intracellular signal transduction system, which results in a biological response that is essential for chemotaxis, cell proliferation, and osteoblastic differentiation. The aim of this study is to determine the efficacy and safety of autologous platelet-rich plasma injection in tennis elbow and plantar fasciitis. We conducted a prospective study with patients who were suffering from plantar fasciitis (n=37) or tennis elbow (n=23) and were given with autologous platelet-rich plasma injection. A short term follow up of all these cases were done at regular intervals for 1, 4, 8, and 12 weeks. The clinical outcomes were analyzed with severity of pain and movements of the pathological part. The functional outcomes were analyzed with VAS and AOFAS scoring for plantar fasciitis and VAS and Mayo’s elbow scoring for tennis elbow. All these patients were statistically analyzed by repeated measures ANOVA test. Our investigation found a statistically significant difference between pre-procedural and post-procedural scores in both the subjective (VAS) and functional (AOFAS and Mayo elbow score) grading systems used in this study. Patients who received an autologous platelet-rich plasma injection experienced a statistically significant (p Autologous platelet-rich plasma acts as a promising efficacious biological therapeutic agent for use in musculoskeletal disorders such as plantar fasciitis and tennis elbow without major complications upon its usage.

The association between Subclinical hypothyroidism and Depression is recognised. It is found that patients with Thyroid disorders are more prone to develop depressive symptoms and depression may be accompanied by various subtle thyroid abnormalities. The most commonly documented abnormalities are elevated T4 levels, Low T3, elevated rT3, a blunted TSH response to TSH, Positive anti thyroid autoantibodies and elevated CSF TRH concentrations. It is also found that thyroid hormone supplements appear to accelerate and enhance the clinical response to antidepressants. It is found out that Depression is associated with changes in Hypothalamic-pituitary axis as thyroid hormones act on the central nervous system. Mild thyroid dysfunction causes depression in younger patients (

Cellular therapy offers regeneration which curbs osteoarthritis of the knee. Among cellular therapies, mesenchymal stromal cells (MSCs) are readily isolated from various sources as culture expanded and unexpanded cellular population which are used as therapeutic products. Though MSCs possess a unique immunological and regulatory profile through cross-talk between MSCs and immunoregulatory cells (T cells, NK cells, dendritic cells, B cells, neutrophils, monocytes, and macrophages), they provide an immunotolerant environment when transplanted to the site of action. Immunophenotypic profile allows MSCs to escape immune surveillance and promotes their hypoimmunogenic or immune-privileged status. MSCs do not elicit a proliferative response when co-cultured with allogeneic T cells in vitro. MSCs secrete a wide range of anti-inflammatory mediators such as PGE-2, IDO, IL-1Ra, and IL-10. They also stimulate the resilient chondrogenic progenitors and enhance the chondrocyte differentiation by secretion of BMPs and TGFβ1. We highlight the various mechanisms of MSCs during tissue healing signals, their interaction with the immune system, and the impact of their lifespan in the management of osteoarthritis of the knee. A better understanding of the immunobiology of MSC renders them as an efficient therapeutic product for the management of osteoarthritis of the knee.

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 field of tissue engineering has revolutionized the world in organ and tissue regeneration. With the robust research among regenerative medicine experts and researchers, the plausibility of regenerating cartilage has come into the limelight. For cartilage tissue engineering, orthopedic surgeons and orthobiologists use the mesenchymal stromal cells (MSCs) of various origins along with the cytokines, growth factors, and scaffolds. The least utilized MSCs are of dental origin, which are the richest sources of stromal and progenitor cells. There is a paradigm shift towards the utilization of dental source MSCs in chondrogenesis and cartilage regeneration. Dental-derived MSCs possess similar phenotypes and genotypes like other sources of MSCs along with specific markers such as dentin matrix acidic phosphoprotein (DMP) -1, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and STRO-1. Concerning chondrogenicity, there is literature with marginal use of dental-derived MSCs. Various studies provide evidence for in-vitro and in-vivo chondrogenesis by dental-derived MSCs. With such evidence, clinical trials must be taken up to support or refute the evidence for regenerating cartilage tissues by dental-derived MSCs. This article highlights the significance of dental-derived MSCs for cartilage tissue regeneration.

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.

Study Design: Systematic review and meta-analysis. Objectives: We performed this meta-analysis to evaluate whether intradiscal Platelet Rich Plasma(PRP) injection has any beneficial role in the management of lumbar disc disease. Methods: We conducted independent and duplicate electronic database searches including PubMed, Embase, and Cochrane Library till September 2020 for studies investigating the role of intradiscal PRP in the management of lumbar disc disease. The analysis was performed in the R platform using OpenMeta[Analyst] software. Results: 13 studies including 2 RCTs, 5 prospective, and 6 retrospective studies involving 319 patients were included in the meta-analysis. A single-arm meta-analysis of the included studies showed a beneficial effect of the intervention in terms of pain relief outcomes like VAS score (p < 0.001), pain component of SF-36 (p = 0.003) while such improvement was not seen in functional outcome measures like ODI score (p = 0.071), the physical component of SF-36 (p = 0.130) with significant heterogeneity noted among the included studies. No structural improvement in magnetic resonance imaging was observed (p = 0.106). No additional procedure-related adverse events were noted in the included studies (p = 0.662). Conclusion: There is a paucity of high-quality studies to give conclusive evidence on the benefits of intradiscal PRP for lumbar disc disease. Although intradiscal PRP injection has shown some beneficial effect in controlling pain for lumbar disc disease, we could not find structural or functional improvement from the included studies. Hence, we recommend large double-blind double-arm randomized controlled studies to analyze the benefits of the intervention being analyzed.

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.

Study design Systematic Review. Objectives We performed this systematic overview on the overlapping meta-analyses that analyzed autologous bone marrow-derived mesenchymal stem cell(BM-MSC) therapy along with core decompression(CD) for the management of osteonecrosis of the femoral head(ONFH) 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 the Database of Abstracts of Reviews of Effects till September 2020 for meta-analyses that analyzed the efficacy of BM-MSC therapy along with CD for ONFH. 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 the highest quality to represent the current best evidence to generate the recommendation. Results 6 meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of the included studies varied from 4 to 9 (mean:7) and all the 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 BM-MSC therapy along with CD for ONFH resulted in significant improvement in Harris hip scores at 12 and 24 months along with a significant reduction in the necrotic area of the femoral head and the rate of conversion to total hip arthroplasty(THA) without a significant rise in adverse events due to the procedure. Conclusion Based on this systematic overview, we give a Level II recommendation that BM-MSC therapy is more efficacious along with CD in the management of ONFH compared to CD alone. BM-MSC therapy provides better pain relief with significant functional improvement and delaying the collapse of the femoral head thereby preventing further treatment such as THA.

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.

Osteo Necrosis of the Femoral Head (ONFH) is a form of osteonecrosis that occurs owing to interruption of blood supply to the proximal femur followed by fragmentation, reossification, and remodelling of the femoral head. In United States, the incidence of avascular necrosis of the femoral head is projected to be around 30000, which contributes to 10% of the total hip replacement done every year. It was believed that necrosis of proximal femur occurs due to the inadequate supply of progenitor cells in the femoral head. So, treatment is aimed at introducing stem cells in necrosis area in order to avoid the risk of fracture and collapse to restore the structural design of femoral head. The objective of this review is to highlight the potential of mesenchymal stem cell (MSC) therapy along with core decompression for the management of ONFH with a special reference to umbilical cord-derived stem cells. Keywords: Umbilical cord, Mesenchymal stem cells, Osteonecrosis, Femoral head, Avascular necrosis.

Introduction: Bizarre parosteal osteochondromatous proliferation (BPOP) presents as painless bony swelling and also known as Nora’s lesion. It is a benign surface osteocartilaginous lesion. This condition is seen most commonly in hands followed by feet. Long bone involvement is rare. Materials and Methods: This is a retrospective study of the patients who had visited the orthopedic OPD of our institute from January 2011 to December 2019. The diagnosis of BPOP was made by radiological evaluation and confirmed by histopathological evaluation. Results: There were 8 cases included in this study. Out of them, 4 cases (50%) were female, and 4 cases (50%) male. The age distribution of patients was 14 years to 36 years. The duration of the history of present illness was 6 months to 3 years. There were 6 cases (75%) of the upper limb and 2 cases (25%) of the lower limb. 4 cases (50%) had a history of trauma. All cases were operated on after pre-operative evaluation and the excisional biopsy specimen was sent for histopathological evaluation for confirmation. On follow up 2 cases (25%) had recurrence for which re-operation was done. Conclusion: BPOP involving long bones is exceedingly rare. The local recurrence rate after surgical resection of the lesion is high. En bloc resection of the lesion along with decortication of the underlying cortical bone was done to reduce the possibility of recurrence. Two patients in our series had a recurrence for which re-operation was done. Keywords: Nora’s lesion, BPOP, Bony swelling, Osteochondramatous proliferation.

Introduction Chronic tendinopathies involves majority of patients in clinical practice of orthopaedic surgeons and sports physicians. The burdens of these problems to a society adversely effect the social, economical,occupational, recreational and physical aspect of patients. Translational medicine confers an emerging medical advances efficiently towards the clinician directly from scientists which may used as a targeted therapy. Objectives: The main objective of translational research from “bench to bedside” is to test novel inventions in humans. Our purpose in this article to understand the translational medicine approach for chronic tendinopathies in clinical aspects. This fulfill the basic objectives of translational science to promote further medical and surgical care with ease. Methods We conducted search in electronic database of google scholar, pubmed ,Embase, web of science, Elsevier and science direct with reviews till October 2020. After obtaining search we narrowed our search for articles in terms of getting a literature specifically mentioned about translational medicine ,translational sciences, chronic tendinopathies. Methodological quality assessment and analysis were done in order to obtain relevantrepresenatation that best suited to our objectives for this article. As this is a narrative review we tried to accommodate important aspect of research and future directives for clinical implications as well as future research in the fields. Discussion: Translational research in chronic tendinopathies is required certainly due to plenty of reasons. Newer advances and targeted approach to these tendon disorders may curtail the further degenerative process. It aids in earlier diagnosis and prevention of morbidity, early occupancy of occupational activity, lack of economical as well as recreational failure. Pre-disease level activity is ultimate goal of any therapy. Current guidelines are lacking in agreement for any single guidelines for tendinopathies. Moreover, there aren’t any clearly defined ideal treatment protocol. Tendon pathophysiology is constantly evolving researched topic in both biochemical as well as molecular aspect. Clinical implications of such emerging techniques and treatments where “bench to bedside” and “bedside to bench” motto of translational medicine should be fastened in order to achieve a newer approach. Conclusions: The basic fundamental understanding of complex process of tendon healing and regeneration is necessary for formulating a newer guidelines. The cornerstone of treatment of tendinopathies is still non-operative management. Physical therapy, better pain control, NSAIDS are still primary choice for these conditions. Various biological therapy whenever used one should combined them with other appropriate options to obtain an optimum outcome.

Objective: Evaluation and management of Tuberculous Pyomyositis, a rare manifestation of Mycobacterium tuberculae. Materials and Methods: All the patients who had visited the orthopaedic OPD at Mahamaya Rajkiya Allopathic Medical College Ambedkar Nagar during the period from March 2012 to March 2019 and diagnosis supported by radiological evaluation by MRI/USG and established by acid fast staining/histopathological evaluation of aspirate/biopsy of involved muscle. Results: Depends upon their clinical presentation initially 28 cases were suspected among which 16 cases (57.10%) found positive for tuberculous pyomyositis. Two patients were lost during follow up so finally there were 14 cases (50%) included in this study. Among 14 cases, 7 cases (50%) were female and 7 cases (50%) male. The age of patients varied from 9 year to 68 year and the duration of illness on presentation from 2 months to 12 months. The routes of infection were hematogenous in 11 cases (78.57%) and penetrating injury in 3 cases (21.42%). All cases were managed with anti tubercular drugs as per guideline, and surgery also needed in 8 cases (72.72%). Conclusion: Isolated presentation of tuberculosis as pyomyositis is rare and not widely reported in the literature. Tuberculous pyomyositis should be considered in long standing vague swelling of the upper and lower limb without constitutional symptoms and signs of inflammations. Thus it is our recommendation is to establish the diagnosis of tubercular pyomyositis followed by anti tubercular treatment; and in selected cases surgical drainage and debridement along with ATT. Keywords: Pyomyositis, Tubercular, Muscle, Infection.

The novel Coronavirus Disease (nCOVID-19) is a highly contagious viral infection which emerged as “Pneumonia of Unknown Etiology” at Hubei province of Wuhan city in China. The health authorities provided a considerable empirical evidence after this outbreak and it was notified that the causative virus, named Novel Coronavirus (subsequently SARS-CoV-2) is the culprit for progressively exerting grim effects not only on individual patients but also on the International public health, with high mutational tendencies. WHO declared nCOVID-19 as a Pandemic on 11th March 2020. The spike glycoprotein of SARS-CoV-2 plays a pivotal role in the entry of virus into the cell and it further interacts with ACE-II receptors which are widely distributed on the human cell surface especially on alveolar type II cells (AT-2) and endothelium. The mortality in nCOVID-19 patients is usually preceded by acute respiratory distress syndrome (ARDS) because of the cytokine storm. Advanced molecular biology and regenerative sciences renders a breakthrough in the treatment of severely ill nCOVID-19 patients with Mesenchymal Stem Cells (MSCs). Autologous or allogenic MSCs attenuate cytokine storm, improvise lung compliance, regulate inflammatory response, maintain functional alveoli microenvironment, promote endogenous regeneration and repair with no or minimal side effects. MSCs are naturally resistant to this novel Coronavirus. Even though it is corroborated with evidences from current clinical trials and pilot study, we emphasize the need for conducting more clinical trials with ethical consideration to prove the efficacy and safety of MSCs in combating nCOVID-19 infection and its complications.

Schizophrenia (SCZ) is a prevalent cause of disability worldwide. Distinguished mainly by psychosis, behavioral alterations could range from hallucinations to delusions. This systematic review examines evidence of a relationship between childhood trauma/adverse life events and psychosis, especially in SCZ. A methodical search provided reproducible results using these five databases: PubMed, ScienceDirect, Semantic Scholar, JSTOR, and Cochrane Library. The systematic search focused on articles published between July 2016 and July 2021. The search strategy utilized specific keywords relevant to SCZ, psychosis, and childhood trauma. The formulation of specified inclusion and exclusion criteria was necessary to ensure a comprehensive narrowed-down search, such as the inclusion of free full-text articles published or translated in English and exclusion of irrelevant subject areas. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a strategic search initially identified 741 articles; three additional articles were identified from citation searching. After relevance screening, duplicate removal, and quality appraisal, 12 studies from databases/registers and three from citation searching met the criteria proving relevance to our review with minimal evidence of bias. The final selected 15 studies included observational studies and reviews. A review of relevant data unveiled findings on childhood adversity, individual lived experiences, and their involvement in SCZ. Evidence suggests that certain neurobiological processes occur in brain after trauma. The inflammation and dysregulation from oxidative stress predispose patients to an at-risk-mental state, facilitating the progression to SCZ. This review encourages further evaluation of early trauma detection and the potential benefits of early intervention.

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.

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.

Hyperglycemia or diabetes mellitus (DM) is a disorder of the endocrine system. In this condition, the body is insulin-deficient or resistant to insulin. Due to insulin deficiency or resistance, the body is unable to process sugar. The worldwide prevalence of diabetes mellitus is rising substantially. Hyperglycemia makes the immune system weak, which increases the risk of infection in a diabetic patient. Fungal infection is more common in DM. Mucormycosis is a rare fungal infection in a healthy individual, but in DM, it can cause severe complications and even be fatal if not treated adequately and timely. In our literature review, a total of 19 published articles from the PubMed database and Google Scholar were included. We combed the PubMed database and Google Scholar by using various inclusion and exclusion criteria. The result of the review study shows the increased risk of mucormycosis in a diabetic patient.

WHO declared SARS-CoV-2 as a pandemic disease on 11th March 2020. Due to global lockdown and restricted social movements, there is a rising curve in the morbidity of health of non- SARS-CoV-2 orthopaedic rheumatology patients and an impairment in the functional quality of life necessitating a pandemic response protocol into action in all fields of patient care. The development of ideal strategies and recommendations for the management of orthopaedic rheumatologically predisposed population and principles to be followed in their practice is the need of the hour. We hereby give a comprehensive list of strategies that can be followed in orthopaedic rheumatology practice by encompassing the recommendations given by the European League Against Rheumatism (EULAR), The American College of Rheumatologists (ACR), and Indian Association of Orthopaedic Rheumatology - Indian Orthopaedic Association (IORA-IOA). SARS-CoV-2 pandemic has put enormous pressure on patients with Rheumatic Diseases (RD) due to their innate weakness and shared treatment protocols in management. Though RD needs a multidisciplinary approach, which remains a challenge in this pandemic scenario, these strategic recommendations would aid in their optimal care amidst the adversity of SARS-CoV-2. Keywords: Orthopaedic Rheumatology, SARSCoV2, COVID19, Rheumatic Diseases.

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.

Background Head and neck cutaneous squamous cell carcinoma (HNCSCC) is a non-melanoma skin cancer that is mostly caused by solar ultraviolet radiation exposure. While it usually has an excellent prognosis, a subset of patients (5%) develops nodal metastasis and has poor outcomes. The aim of this study was to systematically review the literature and evaluate the prognostic factors of HNCSCC in order to better understand which patients are the most likely to develop metastatic disease. Methods A comprehensive literature search was performed on PubMed and EMBASE to identify the studies that evaluated the prognostic factors of HNCSCC. Prognostic factors were deemed significant if they had a reported p-value of Results The search yielded a total of 958 citations. Forty studies, involving a total of 8535 patients, were included in the final analysis. The pre-operative/clinical prognostic factors with the highest proportion of significance were state of immunosuppression (73.3%) and age (53.3%); while post-operative/pathological prognostic factors of importance were number of lymph nodes involved with carcinoma (70.0%), margins involved with carcinoma (66.7%), and tumor depth (50.0%). Conclusion This systematic review is aimed to aid physicians in assessing the prognosis of HNCSCC and identifying the subsets of patients that are most susceptible to metastasis. It also suggests that immunosuppressed patients with a high-risk feature on biopsy, such as invasion beyond subcutaneous fat, could possibly benefit from a sentinel lymph node biopsy. Graphical abstract

Tuberculous tenosynovitis is a chronic and rare infection of flexor tendon sheath of forearm, mainly around the wrist. Patients presents with swelling and pain, and sometime also with neurological symptoms when median nerve get involved. Patient evaluated clinically for the diagnosis, but the MRI is the gold standard tool for the diagnosis. Histopathological evaluation is also needed to confirm the diagnosis. Management is mainly surgical followed by full course of anti tubercular therapy. A delay in the management may leads to complications due to asymptomatic swelling. Keywords: Wrist swelling, Compound palmar ganglion, Tubercular tenosynovitis, Melon seeds, Median nerve.

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.

STUDY DESIGN: Meta-analysis. OBJECTIVES: We aim to identify the clinically significant ideal Mesenchymal Stem Cell (MSC) count in the management of osteoarthritis of 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 conducted in the management of knee osteoarthritis using MSC therapy specifying the quantity of MSCs delivered. We categorized the studies based on the MSC count utilized in them into four groups namely 10 × 10(7) MSCs (Group IV). Visual Analog Score (VAS) for Pain, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Lysholm score, Knee Osteoarthritis Outcome Score (KOOS), and adverse events were the outcomes analyzed. Analysis was performed in R-platform using OpenMeta [Analyst] software. RESULTS: 14 studies involving 564 patients were included for analysis. We noted incremental decrease in the VAS with increasing dosage of MSCs at 12 months [Group I,WMD = 2.641(p = 0.854); Group II, WMD = −4.853(p = 0.379); Group III, WMD = −12.154 (p = 0.316); Group IV, WMD = −15.935(p = 0.116)], and 24 months [Group I,WMD = −6(p = 0.001); Group II, WMD = −15(p = 0.001); Group IV, WMD = −20(p = 0.001)]. We also noted incremental improvement in the WOMAC, KOOS with increasing dosage of MSCs at 12 months [Group I, WMD = 7(p = 0.001); Group II, WMD = 28(p = 0.001); Group IV, WMD = 30(p = 0.001)] and [Group II, WMD = −2.562(p = 0.676); Group III, WMD = 7.670(p = 0.099); Group IV, WMD = 13.475(p = 0.261)] respectively. However, we noted significant reduction in the Lysholm score in Group IV, compared to the others at 12 months (WMD = −12.5, 95%CI[-25.883,0.883]) and 24 months (WMD = −6.6, 95%CI[-23.596,10.396]). We did not find any significant increase in the adverse events with incremental dosage of MSCs in any of the groups compared. CONCLUSION: Compared to the four dosage groups of MSCs analyzed, Group III showed consistent significant improvement in pain and functional outcomes analyzed compared to the other groups. Hence, we recommend a cell volume of 5-10 × 10(7) cells to be delivered to the target site to obtain superior benefits out of the procedure. However, we urge future trials of sufficient quality to validate our findings to arrive at a consensus on the ideal count of MSCs to be delivered in the cellular therapy for knee osteoarthritis.

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

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.

Liquefaction and related phenomenon have been in charge of enormous measures of harm in recorded seismic tremor all over the world. The city Jalandhar is under zone IV. It sustains the vulnerability of city to seismic forces. A number of multistoried high-rise buildings are under progress and several high-rise buildings are proposed for next few years. From the study of past earthquakes, we have demonstrated that liquefaction-induced ground failure may pose catastrophic damage threats to rural and urban infrastructure including buildings. To fulfill the safety purpose it is imperative that the new structure in Jalandhar be analyzed for seismic forces. To fulfill the need of the objective, the area was analyzed with the help of simplified procedure given by Seed and Idriss (1971) of liquefaction potential evolution is used. With the use of SPT result, ground response analysis has been done. Peak ground acceleration has been calculated using software. The estimated peak ground acceleration will be used to check liquefaction of specific sites in Jalandhar. The bore log data has been obtained from 10 locations of Jalandhar. From this analysis, it is obtained that there are only two sites which are likely to be effected under liquefaction.

The linchpin for COVID-19 pathogenesis is the severe inflammatory process in the respiratory tract wherein the accumulation of excessive cytokines paves the way for a series of systemic hemodynamic alterations and mortality. The mortality rate is higher in individuals with co-morbidities and advancing age. The absence of a specific therapy is responsible for this uncontrolled spread and the significant mortality. This renders potential insight for considering biologics as a plausible option to repair and regenerate the affected lung tissue and pulverize the causative organism. The plausible role of megakaryocytes against invading microbes was not clearly understood. Platelet lysate is an acellular product consisting of regenerative molecules released from a cluster of platelets. It attenuates the changes caused by immune reactions in allogenic utility with the introduction of growth factors, cytokines, and proteins at supraphysiologic levels and thereby serves as a regenerative immunomodulatory agent to combat COVID-19. This platelet lysate can be used in nebulized form for such acute respiratory distress conditions in COVID-19 elderly patients. Platelet lysate may emerge as a pivotal player provided investigations pace up in this context. Here, we discuss how the platelet lysate can plausibly perquisite to relegate COVID-19. Undertaking prospective randomized controlled trials to prove its efficacy is the need of the hour in this pandemic scenario.