Coronavirus disease-19 (COVID-19), a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is a primarily respiratory tract disease. Suitable animal models for COVID-19 are required to study various aspects of pathogenesis, drug discovery, effective and safe vaccine development. Several laboratory animals including, non-human primates, hamsters, ferrets, transgenic mice, and zebrafish, have been used and proven their significance experimentally. Currently available animal models of SARS-CoV-2 can be broadly classified into two categories 1) natural animal models 2) genetically-modified that exhibit different degrees of susceptibility of SARS-CoV-2, tissue damage in respiratory and other organ systems. Not all the available animal models mimic COVID-19-like phenotype completely. Therefore, understanding various aspects of COVID-19 requires different animal models. In this review article, we provide an update on the immune response and clinical manifestations observed in naturally occurring and genetically-modified animals of COVID-19. We then review the transmission, viral replication, lung pathology, immunological aspects, and extrapulmonary phenotypes observed in various animal models. In the end, we put forth our perspective on the anticipated uses, disadvantages, and limitations of each type of animal model.

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has caused Coronavirus disease-2019 (COVID-19), the worst pandemic of the 21st century. Globally, millions of lives have been lost due to COVID-19. Transmission of SARS-CoV-2 occurs human-to-human through air droplets. SARS-CoV-2 is thought to originate from a bat Coronavirus, which might have reached human beings through intermediate hosts. SARS-CoV-2 causes a variable degree of illness in human beings, including patients being an asymptomatic, mild, moderate, and severe disease, which requires hospitalization. The common symptoms of COVID-19 include fever, cough, myalgia, dyspnea, sore throat, anosmia, ageusia, and diarrhea. The pathogenesis of COVID-19 involves the attachment, entry, and replication of the virus in the host cells. The gains entry into human cells through engagement of angiotensin-converting enzyme 2 receptor with its spike proteins. The overproduction of highly inflammatory cytokines results in a cytokine storm, leading to an increased risk of acute respiratory distress syndrome, coagulopathy, and multiorgan failure. This chapter provides insight into the epidemiology, transmission, and pulmonary and extrapulmonary pathogenesis of COVID-19.

To evaluate the safety and efficacy of a novel technique of preconditioning autologous blood with gold particles (GOLDIC®) and injection in patients with moderate to severe knee osteoarthritis (KOA). During this phase 2a, proof-of-concept (PoC) open label study, 83 consecutive patients that 64 patients met inclusion criteria (mean age: 64.8 years; 89 knees) with radiographically proven KOA, received four ultrasound guided intra-articular knee injections of GOLDIC® at three to six day intervals. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee injury and Osteoarthritis Outcome Score (KOOS) were evaluated at baseline, four weeks, three, six months, one, two and four years (T1–T6). The incidence of treatment related severe adverse events (SAEs) recorded. Intra-articular gelsolin level in patients with effusion was determined. KOOS and WOMAC scores improved for the full duration of the study (P < 0.05), minimal clinically important difference (MCID) was observed at all time points in all KOOS subscores, with no reported SAEs. Intra-articular gelsolin level increased after treatment with reduction of effusion. No statistically significant evidence of an association between patient demographics and outcome were identified. Nine patients failed treatment, with 32 months mean time to failure and underwent total knee arthroplasty. PoC study of GOLDIC® as a novel device for conservative management of moderate to severe KOA was confirmed. GOLDIC® produces rapid and sustained improvements in all indices after treatment, with no SAEs. § 13 Abs.2b AMG Bavaria (Protokol Reg OBB 5-16) (Ref 53.2-2677.Ph_3-67-2)—Date 3/20/2010 retrospectively registered.

COVID-19 pandemic has brought the whole world stand still, locked down in their homes, infecting more than 8 million people, and many thousands (449,182) -have lost their lives across the globe. Due to lack of any definitive medicine or vaccine, treatment options arc supportive of oxygenation, antiviral, antiretroviral drugs, antibiotics, fluid/electrolyte, mechanical ventilation with ICU (Intensive Care Unit) support, and chloroquine/hydroxychloroquine = have been tried to fight this infection. However, mortality due to severe pneumonia, ARDS (Acute Respiratory Distress Syndrome), and multiorgan failure arising from the overactive immune response (storm) mediated by cytokines remains a treatment challenge in elderly and patients with severe medical comorbidities. Recently, anti-inflammatory, angiogenic, immune-modular, and healing properties of intravenous injections of culture derived stern cells have been proposed and shown to benefits in a small number of patients with severe COVID-19 infections. Based on previous experience with other viral infections, convalescent plasma, and serum transfusion are being used as a source of neutralizing antibody/factors to minimize the effects of inflammatory cytokines in this infection. Immunotherapy with purified monoclonal antibodies and conditioned serum with a mixture of unique cytokines are also being developed. Regenerative Medicine has emerged as a crucial adjuvant tool in promoting healing and early recovery in severe COVID-19 infections and other supportive treatments.

Mesenchymal Stem Cell (MSC) therapy in osteoarthritis has been hailed as a promising treatment for osteoarthritis due to their unlimited potential of healing and regeneration. Existing literature regarding their proper name, optimal sources, mechanisms of action, dosage, and route of administration, efficacy, and safety is debatable. This index review article has tried to connect these puzzling pieces of available information and brought clarity on some of these crucial issues. The author believes that Maintenance Stem Cells (MSC) may be a more suitable term than mesenchymal stem cell or medicinal signaling cells as their origin might not be limited to mesodermal tissue. Also, they have been shown capable of self-renewal, differentiation, and maintaining a cascade of healing & possibly regeneration at the implanted site. Only a small percentage of implanted MSC survive and rest undergo apoptosis after releasing growth factors, cytokines, and extracellular vesicles. These surviving MSC become active due to conformational changes induced by anti-environment stimuli and undergo limited self-renewal, proliferation, and differentiation, but only a few of them might incorporate into the host tissues. These cells generate & maintain a momentum of series of regenerative activities to improve the function of joint, stabilize or possibly enhance the cartilage quality. More randomized studies with long term follow-up are required to bring clarity on their ideal source, expansion, culture technique, optimum dosage, and route of administration and long-term safety issues.

BackgroundComparative studies of platelet-rich plasma (PRP) and hyaluronic acid show variable results. PurposeA review was conducted to understand the current role of PRP and its efficacy versus hyaluronic acid in osteoarthritis (OA) of the knee joint. MethodsOut of 170 identified studies, 14 studies involving 1575 patients with 637 males and 938 females were selected based on PRISMA flow chart guidelines and were analyzed for the study. ResultsA standard PRP regimen consisting of 2–3 intra-articular injections (IA) of 4–6 mL of leucocyte poor PRP at 1–2 weekly intervals provides a better result than HA during the first 3–6 months, and which may continue up to one year. PRP and HA may have synergistic effect; pain and swelling are the two most com-mon complications with PRP, the incidence is more with leucocyte rich PRP (LP-PRP) and intra-osseous PRP treatment.ConclusionPRP provides hope and is more effective than hyaluronic acid in pain relief and improving the quality of life in mild to moderate osteoarthritis of the knee joint. However, hype, that is effective in all, irrespective of grades of OA, mal-aligned or stiff knee, ligamentous laxity, and can avoid joint replacement is a big hindrance in establishing it as a preferred treatment in OA knee. The author follows the above-mentioned PRP regimen; and recommends to combine leucocyte poor PRP with HA for IA injections & with LP-PRP injections along with the two most common painful points (medial collateral ligament, pesanisernius) in a highly painful OA knee. PRP may not address extra-articular causes of knee pain (mal-alignment, muscle wasting, tendinosis), should be corrected for optimum outcome. Contact sports, running, exercises putting pressure on knee and NSAID should be avoided during PRP treatment. Also, more randomized controlled trials are required to further standardize the PRP preparation, administration, injection interval & proper documentation of efficacy and complications in the regenerative registry.

BACKGROUND:To assess a new modification of posterior approach to the hip and its effect on stability and functional outcome in total hip arthroplasty.MATERIAL & METHODS:A comparative retrospective study was done to assess the functional outcome and rate of dislocation among 233 hips (Group A) operated by conventional posterior approach and 567 hips (Group B) by our novel modified posterior approach. In this technique, 2-3 stay sutures are applied in external rotators, then a single conjoint-myocapsular sleeve is raised linearly over the capsule with adherent fibers of gluteus minimus to piriformis tendon, short rotators and part of quadratus for exposure of femoral head. After inserting the definite prosthesis, upper part of sleeve (capsule, piriformis tendon) is sutured at the lower part of tip of greater trochanter & lower part with lateral trochanteric bone. Fifty patients, using randomised tables, in group B underwent MRI to evaluate the efficacy of the repair at 1 and 12 weeks postoperatively.RESULTS:Average Harris hip score at minimum 3.9 year follow up was 83.2 in Group A & 88.7 in Group B. Group B had only one dislocation (0.176%) while Group A had 12 dislocations (5.15%). MRI showed intact repair in 47 patients (94%); fibrous continuity in 2 patients (6%) in group B patients.CONCLUSION:Intermediate results shows that this technique provides enhanced stability and improved functional outcome. But more prospective and randomised controlled studies with long term followup are required to confirm its role in prevention of hip dislocations.

The economic and human cost of knee osteoarthritis is forecast to increase. This will impact not only aging individuals, but also the working age members of emerging economies. The current treatment pathways are often costly, time-consuming, and insufficient to manage the degeneration of the knee over the ever-increasing lifespan of patients around the world. In response to the shortcomings of a focus on symptom management, international and high-impact regulators, researchers, clinicians, and most importantly patients, are increasingly interested in the possible management of knee osteoarthritis with novel therapies in the field of regenerative medicine treatments. Regenerative medicine is an emerging discipline whose adherents aim to use the tools of the human body to address underlying dysfunction, leading to lasting repair of damaged tissues and structures. The evidence base lacks consensus on issues related to safety, efficacy, cost-efficiency, and treatment specifications. In this current concepts review, we describe the potential impact of regenerative medicine for knee osteoarthritis and evaluate literature of the past decade for elements related to the quality of clinical research. Finally, we discuss strategies for improving the evidence base for the future. The results of the review reveal that the typical follow-up period for most clinical research into the area is between 6 and 12 months; local ethics board approval is commonly reported, and that Platelet-Rich Plasma is the most common option explored. However, several quality elements were lacking in this cohort of recent literature: cost efficacy data, long-term follow-up, and detailed adverse event reporting. In order to address these weaknesses in the literature, patient outcomes registries are needed, in order to satisfy the need for longer follow-up for individuals receiving regenerative treatments, in addition to further clinical trials which address larger and more diverse patient populations. Transparency will be of utmost importance in further research and clinical translation of regenerative medicine for knee osteoarthritis.

Osteochondromas are the most common bone tumours. Although these tumors are relatively common in the long bones of children, the varied clinical and radiographic presentation of such neoplasms around the knee joint can cause diagnostic delays, especially when not associated with a palpable swelling. Proximal tibial osteochondromas can sometimes unusually present as spurs/ rose thorns leading to pes anserinus bursitis and vague knee pain. We describe the clinico-radiographic features of such proximal tibial metaphyseal osteochondromas giving rise to pes anserinus bursitis in three children, including bilaterally symmetrical osteochondroma in one of the cases, who were treated conservatively with good outcomes.

Background: Factors influencing publication of manuscripts in reputed journals have never been studied to the best of our knowledge. This study was conducted to evaluate the trend in publication within the Indian Journal of Orthopaedics (IJO).Materials and Methods: A cross-sectional study was conducted by accessing the online database of the IJO. All the issues available online were included. Published articles were classified into one of the following thirteen categories: (i) Basic Sciences (ii) trauma (upper limb and lower limb) (iii) infections (iv) pediatric orthopedics (v) arthroplasty (vi) arthroscopy (vii) spine surgery (viii) musculoskeletal oncology (ix) hand and microvascular surgery (x) adult reconstruction (including the Ilizarov technique) (xi) general orthopedics and miscellaneous (xii) letter to editor (xiii) book review. A scatter diagram was plotted to study the individual trends.Results: A total of 2213 articles from 110 issues published between 1967 and 2014 were studied. Total number of articles per issue have increased over the years. Publications in the fields of trauma, adult reconstruction, arthroscopy and hand and microvascular surgery have increased steadily. Arthroplasty and spine surgery have recorded dramatic increase in publication. On the other hand, publications in the rest of the fields have declined of which the greatest fall is noted in the field of musculoskeletal oncology.Conclusions: Trend in publication with the IJO has changed over years with more articles being published in arthroplasty and Spine surgery. Despite advances, publication in the field of musculoskeletal oncology has fallen.

Purpose Tuberculosis of the hip joint is a significant cause of preventable disability, especially in children. The aim of our study was to evaluate the functional results of hip arthroscopy done in a cohort of patients with hip joint tuberculosis and to compare them with the outcome of conservatively managed cases. Methods This was a retrospective cohort study in which we evaluated the records of 22 hip arthroscopies performed in known cases of tuberculosis of the hip joint in children less than 12 years of age. A note of the demographic and clinical parameters like age, duration of symptoms, stage of the disease, time period of follow-up, any complications during surgery, and pre- and post-operative modified Harris hip score (MHHS) was made in all cases. We compared the results with an age-matched cohort of 44 children with hip joint tuberculosis who were treated non-operatively with anti-tuberculosis therapy and traction in the same tertiary care institute. Results The arthroscopic findings in our series included synovitis, chondral erosions of the femoral head and/or acetabulum, pannus formation over the femoral head and/or acetabulum, and labral tears. The various arthroscopic procedures which were done included joint lavage, synovectomy, labral debridement and cheilectomy. The mean follow-up was 45 months, with the minimum being 36 months. There was a statistically significant change in the mean MHHS after hip arthroscopic procedures ( p < 0.001); the difference in the mean post- and pre-operative MHHS was independent of age, stage or duration of follow-up. There was a statistically significant difference ( p < 0.05) between the magnitude of improvement in MHHS after hip arthroscopy and that after conservative management. Conclusions Arthroscopy of the hip joint in children in cases of tuberculosis can serve as an emerging therapeutic modality. It is an effective and safe minimally invasive procedure, and helps in improving the functional outcome in early disease.

Complications involving the extensor mechanism after TKA are potentially disastrous. We are reporting a case of patellar tendon rupture from tibial tuberosity following total knee arthroplasty. We managed it by direct repair with fiberwire using Krackow suture technique without augmentation. Our long term result has been very encouraging. Our method is a safe and better method of management of patellar tendon avulsion following TKA when it happens without any tissue loss.

AIM:Thigh pain following tourniquet application is a common complaint in early post operative period following total knee arthroplasty.METHOD:Post operative Thigh pain was evaluated in 30 consecutive simultaneous bilateral total knee arthroplasty patients between July 2013 and January 2014. Patient thigh pain was evaluated with the VAS score. The scale was applied on first, second, third day & second and six weeks after surgery.RESULT:There were statistically significant difference in VAS score in non-tourniquet group on first, second, third post operative day. We did not find statistically significant difference at Second and Six weeks post operatively.CONCLUSION:This Randomized trial demonstrates that non-tourniquet use in TKA has less early postoperative pain and leads to better recovery.

Bizarre parosteal osteochondromatous proliferation (BPOP; also called Nora's lesion) is a benign surface osteocartilaginous lesion, which is infrequently reported in world literature. The condition is classically described in the short tubular bones of hands and feet in the second and third decades of life. We present a case report of BPOP of the middle phalanx of middle finger in a 4-year-old girl. The child underwent a wide excision and remained asymptomatic at 2.5 years of follow-up. Our case report highlights the importance of suspecting Nora's lesion in a child. It also helps in delineating a differential diagnosis and discusses the management principles of this rare osteocartilaginous lesion.

OBJECTIVE:To present our experience in treatment of difficult ununited long bone fractures with locking plate.METHODS:Retrospective evaluation of locking plate fixation in 10 difficult nonunions of long bone fractures was done. Fixation was done with locking plate for femoral shaft fracture (3 patients), supracondylar fracture of femur (gap nonunion), fracture of clavicle, fracture of both forearm bones (radius and ulna) fracture of ulna, fracture of shaft of humerus, fracture of tibial diaphysis and supracondylar fracture of humerus (one patient each). Five fractures had more than one previous failed internal fixation. One patient had infected nonunion which was managed by debridement with cast immobilization followed by fixation with locking plate at six weeks. Seven fractures were atrophic, two were oligotrophic, and one was hypertrophic. Fibular autograft was used in 2 cases and iliac crest cancellous bone graft used in all the patients.RESULTS:Minimum follow-up was 6 months (range, 6 months to 2.5 years). Average time for union was 3.4 months (range 2.5 to 6 months). None of the patients had plate-related complications or postoperative wound infections.CONCLUSION:Along with achieving stability with locking compression plate, meticulous soft tissue dissection, acceptable reduction, good fixation technique and bone grafting can help achieve union in difficult nonunion cases. Though locking plate does not by itself ensure bony union, we have found it to be another useful addition to our armamentarium for treating difficult fracture nonunions.

Tears of the medial meniscus posterior root can lead to progressive arthritis, and its management has no consensus. The aim of our study was to evaluate the effect of supervised exercise therapy on patients with medial meniscus posterior root tears.

We present the technical report for treatment of comminuted fracture of the capitate with ligamentotaxis. The base of third metacarpal was found to be fractured with comminution of the capitate. The decrease in carpal height index and comminution of the third metacarpal base lead to dilemma between conservative treatment and surgical management of this particular injury. The surgical management was chosen to maintain the carpal height index of the wrist to prevent the late degenerative changes.The patient was applied with external fixator in distraction mode expanning the wrist joint for six weeks, and the wrist was mobilised after removal of the fixator. It is shown that the external fixator in distraction mode expanning the wrist joint is a good alternative method for treatment of capitate fracture.

Conventionally described standard techniques of forequarter amputation may not be suitable for patients presenting with neglected or maltreated very large tumors of the proximal humerus.