Serum Osteopontin as a Potential Marker for Metastasis and Prognosis in Primary Osteogenic Sarcoma: A Systematic Review.

Osteosarcoma (OS), a primary malignant bone tumor, poses significant challenges in diagnosis and prognosis. It is a painful medical burden, and treating it is still a difficult issue. Osteopontin (OPN), a multifunctional extracellular matrix protein, has emerged as a promising biomarker in this context. This systematic review explores the role of OPN as a diagnostic and prognostic marker in OS, highlighting its potential in enhancing early detection, monitoring disease progression, and predicting patient outcomes. Various studies have demonstrated elevated levels of OPN in OS patients, correlating with tumor aggressiveness, metastatic potential, and poor prognosis. In addition, OPN's involvement in tumor microenvironment regulation and metastatic processes underscores its clinical relevance as a biomarker. For this systematic review, comprehensive literature searches were conducted in the PubMed databases for research published between the database's establishment and November 11, 2022. Out of the nine studies that were available for analysis, a higher level of OPN in primary osteogenic sarcoma patients indicates a poorer prognosis and higher incidence of metastasis. OS has not shown commensurable progress with concerns to treatment approches and survical outcomes. However, the discovery of a biological marker that can predict metastasis and severity will be a groundbreaking development for advancements in OS diagnosis and treatment. Therefore, understanding the intricate interplay between OPN and OS pathogenesis holds promise for improving patient management and developing targeted therapeutic strategies.

A Comparison of the Clinicoradiological Outcomes of Intertrochanteric Fractures Treated Using Proximal Femoral Nail and Proximal Femoral Nail Anti-rotation.

Background Managing intertrochanteric fractures presents challenges for orthopedic surgeons, not only in fixing the fracture but also in preventing and managing associated complications, especially in the vulnerable geriatric population. Cephalomedullary nails are commonly used for surgical fixation due to their favorable functional profile, which preserves the hip's abductor lever arm and proximal femur anatomy. However, there's a lack of data comparing two major options: proximal femoral nail (PFN) and proximal femoral nail anti-rotation (PFNA). This study aimed to compare the radiological fracture reduction and fixation as well as functional outcomes of these two implants in treating intertrochanteric fractures. Methods The study, spanning 24 months, involved a prospective comparative design. Participants included patients diagnosed with intertrochanteric femur fractures classified as AO Type 31 A1, AO Type 31 A2, and AO Type 31 A3. Fifty patients were evenly distributed into PFN and PFNA groups. Preoperatively, clinical and radiological assessments were conducted, along with serum vitamin D level measurements. Surgeries, performed under anesthesia with image intensifier guidance, followed defined reduction and implant insertion protocols for each group. Postoperatively, evaluations were conducted up to six months, examining parameters such as tip-apex distance (TAD), Cleveland index, and modified Harris hip score, while documenting intraoperative duration and blood loss. Data analysis utilized the statistical software Statistical Package for Social Sciences (SPSS), version 22.0 (IBM Corp., Armonk, NY), employing descriptive statistics, chi-square tests, independent t-tests, and paired t-tests, with significance set at p < 0.05. Results In our study, 50 patients were enrolled, with equal gender distribution (64.0% male, 36.0% female, p=1.000). The mean ages in the PFN and PFNA groups were 66.2 ± 9.8 years and 66.4 ± 11.3 years, respectively (p=0.936). All fractures united by six months, with no implant-related complications reported. PFNA showed significantly lower blood loss and shorter surgery durations (p<0.001). TAD and neck shaft angle were similar between groups (p=0.826, p=0.555). Cleveland index placement and modified Harris hip score improvement were comparable (p=0.836, p<0.001). Predominant vitamin D deficiency was observed in both groups. Conclusion PFNA offers measurable intraoperative benefits over conventional PFN in terms of operative time, blood loss, and need for fluoroscopic imaging. However, no statistically observable benefits were noted in postoperative functional outcomes or complications between the two implants.

C-reactive protein lowers the serum level of IL-17, but not TNF-α, and decreases the incidence of collagen-induced arthritis in mice.

The biosynthesis of C-reactive protein (CRP) in the liver is increased in inflammatory diseases including rheumatoid arthritis. Previously published data suggest a protective function of CRP in arthritis; however, the mechanism of action of CRP remains undefined. The aim of this study was to evaluate the effects of human CRP on the development of collagen-induced arthritis (CIA) in mice which is an animal model of autoimmune inflammatory arthritis. Two CRP species were employed: wild-type CRP which binds to aggregated IgG at acidic pH and a CRP mutant which binds to aggregated IgG at physiological pH. Ten CRP injections were given on alternate days during the development of CIA. Both wild-type and mutant CRP reduced the incidence of CIA, that is, reduced the number of mice developing CIA; however, CRP did not affect the severity of the disease in arthritic mice. The serum levels of IL-17, IL-6, TNF-α, IL-10, IL-2 and IL-1ß were measured: both wild-type and mutant CRP decreased the level of IL-17 and IL-6 but not of TNF-α, IL-10, IL-2 and IL-1ß. These data suggest that CRP recognizes and binds to immune complexes, although it was not clear whether CRP functioned in its native pentameric or in its structurally altered pentameric form in the CIA model. Consequently, ligand-complexed CRP, through an as-yet undefined mechanism, directly or indirectly, inhibits the production of IL-17 and eventually protects against the initiation of the development of arthritis. The data also suggest that IL-17, not TNF-α, is critical for the development of autoimmune inflammatory arthritis.

Forecasting of Indian tourism industry using modeling approach.

Currently, India has become one of the largest economies of the world in which tourism and hospitality have significantly contributed; however, the growth rate of tourism industry has been greatly affected during the COVID-19 pandemic. In this study, we have used the modeling approach to analyze and understand the growth pattern of Indian tourism industry. To achieve this, we consider the data of international tourist arrivals before and after the lockdown. The Dickey-Fuller test, AIC and BIC methods are used to obtain the best fitted model and further, the accuracy of obtained model is also analyzed. Data and forecasting indicate that the weather and public holidays significantly affect the tourism industry.

Experience of patients on methadone maintenance treatment receiving take-home methadone doses during COVID-19 pandemic: A multi-site study from India.

BACKGROUND: Methadone take-home doses for opioid dependence treatment are strictly regulated due to diversion and overdose concerns, so patients must visit the clinic daily for dispensing. This was also done in India until the COVID-19 pandemic, when lockdown restriction compelled take- home dispensing of methadone. This study examined experience of patients who received take- home methadone during COVID-19 pandemic in India. METHODS: Observational, cross-sectional design. We contacted all consenting methadone centres in India during the lockdown and selected those that provided take-home doses for the study. Patients who received daily methadone before the lockdown and take-home doses after were interviewed using a study-specific questionnaire. RESULTS: The study had 210 participants. Take-home methadone was dispensed for 2.5 days on average in each dispensing. When taking methadone at home, 3.3% split their dose 25% took less than the prescribed dose to save it for a rainy days, and 3.3% reported an overdose episode. Adherence improved in 58.6% participants after take-home methadone. Participants perceived many benefits from take-home methadone such as reduced hospital visits and travel time to collect methadone, improvement in work, and financial savings. About 54.3% participants reported storing their take-home doses safely, and 1.9% reported that their family consumed methadone by mistake. CONCLUSIONS: Take-home methadone was found to be beneficial to most participants in terms of time saved and improved productivity. Preconceived concerns of providing take-home methadone in terms of its overdose, diversion, or accidental ingestion by others are not commonly seen when individuals are provided take-home doses of methadone.

Epidemiology of Osteoporosis.

Background: India has a population capacity of 1.2 billion people. With a worldwide aging population, the prevention and management of osteoporosis has become a significant healthcare challenge. It is crucial to recognize the factors impacting poor bone health and appreciate the many hurdles to treat the disease to provide a better quality of life and decrease the financial burden on healthcare. Purpose: In this review article, we discuss the epidemiology of osteoporosis and address the definition, incidence, and prevalence, geographical variation in the occurrence of osteoporosis, and the risk factors for osteoporosis. Methods: Search terms using various combinations of the keywords 'osteoporosis,' 'epidemiology,' 'incidence,' 'prevalence,' 'fracture,' 'India,' 'world,' 'screening,' and 'FRAX' was done to review all relevant literature till June 2023. Results & Conclusion: India has a recent estimate of population capacity of 1.2 billion people. Various studies have revealed an osteoporosis prevalence in Indian women ranging from 8% to 62%. Poor dietary calcium intake, low vitamin D, and lifestyle changes contribute to osteoporosis.

Total Hip Arthroplasty in Neglected Acetabular Fracture with Pipkin Type 4 Femoral Head Fracture. A Case Report.

Introduction: Pipkin type 4 fracture is defined as hip dislocation with femoral head fracture and concomitant acetabular rim fracture. These fractures are rare. Neglected fractures develop adaptive changes in the acetabulum, femoral head, and soft tissues around the hip joint, leading to hip arthritis. Total hip arthroplasty is preferred in such cases. After an extensive literature review, we did not find any guidelines for managing neglected Pipkin type 4 fractures. Case Report: A 47-year-old male presented with pain in his left hip and an inability to bear weight on his left lower limb. He had a road traffic accident 1 year ago. On clinical examination, there was a shortening of 3 cm and reduced hip range of motion on 3D computed tomography posterosuperior defect of the acetabular wall along with Pipkin type 4 femoral head fracture was detected. Total hip arthroplasty with acetabular reconstruction using a femoral head autograft was done. At 1 year of follow-up, the patient was pain-free and could walk without any assistance with a normal gait. Conclusion: Uncemented total hip arthroplasty with an autologous structural femoral head graft is a suitable method of treatment for neglected Pipkin type 4 fractures. It preserves bone stock and does not add any financial burden.

Short-term Follow-up of Autologous Adult Live-Cultured Osteoblasts Implantation in Avascular Necrosis of Femoral Head Secondary to Sickle Cell Anemia-Case Series.

Introduction: The prevalence of avascular necrosis (AVN) of the femoral head in sickle cell anemia is 50% whereas untreated cases lead to total hip replacement. The recent development in cellular therapy paves the way to utilize autologous adult live-cultured osteoblasts (AALCO) in the management of AVN of the femoral head secondary to sickle cell anemia. Case Report: We performed AALCO implantation in sickle cell anemia cases with AVN of the femoral head and were followed up for 6 months with the regular recording of visual analog score and modified Harris Hip Score. Conclusion: AALCO implantation for the management of AVN of the femoral head due to sickle cell anemia appears to be the biological management of choice as it results in pain reduction and improvement in function.

Structurally Altered, Not Wild-Type, Pentameric C-Reactive Protein Inhibits Formation of Amyloid-ß Fibrils.

The structure of wild-type pentameric C-reactive protein (CRP) is stabilized by two calcium ions that are required for the binding of CRP to its ligand phosphocholine. CRP in its structurally altered pentameric conformations also binds to proteins that are denatured and aggregated by immobilization on microtiter plates; however, the identity of the ligand on immobilized proteins remains unknown. We tested the hypotheses that immobilization of proteins generated an amyloid-like structure and that amyloid-like structure was the ligand for structurally altered pentameric CRP. We found that the Abs to amyloid-ß peptide 1-42 (Aß) reacted with immobilized proteins, indicating that some immobilized proteins express an Aß epitope. Accordingly, four different CRP mutants capable of binding to immobilized proteins were constructed, and their binding to fluid-phase Aß was determined. All CRP mutants bound to fluid-phase Aß, suggesting that Aß is a ligand for structurally altered pentameric CRP. In addition, the interaction between CRP mutants and Aß prevented the formation of Aß fibrils. The growth of Aß fibrils was also halted when CRP mutants were added to growing fibrils. Biochemical analyses of CRP mutants revealed altered topology of the Ca2+-binding site, suggesting a role of this region of CRP in binding to Aß. Combined with previous reports that structurally altered pentameric CRP is generated in vivo, we conclude that CRP is a dual pattern recognition molecule and an antiamyloidogenic protein. These findings have implications for Alzheimer's and other neurodegenerative diseases caused by amyloidosis and for the diseases caused by the deposition of otherwise fluid-phase proteins.

IL-6 regulates induction of C-reactive protein gene expression by activating STAT3 isoforms.

C-reactive protein (CRP) is synthesized in hepatocytes. The serum concentration of CRP increases dramatically during the acute phase response. In human hepatoma Hep3B cells, maximal CRP expression occurs in cells treated with the combination of IL-6 and IL-1ß. IL-6 induces transcription of the CRP gene and IL-1ß synergistically enhances the effects of IL-6. We investigated the role of IL-6-activated transcription factor STAT3, also known as STAT3α, in inducing CRP expression since we identified four consensus STAT3-binding sites centered at positions - 72, - 108, - 134 and - 164 on the CRP promoter. It has been shown previously that STAT3 binds to the site at - 108 and induces CRP expression. We found that STAT3 also bound to the other three sites, and several STAT3-containing complexes were formed at each site, suggesting the presence of STAT3 isoforms and additional transcription factors in the complexes. Mutation of the STAT3 sites at - 108, - 134 or - 164 resulted in decreased CRP expression in response to IL-6 and IL-1ß treatment, although the synergy between IL-6 and IL-1ß was not affected by the mutations. The STAT3 site at - 72 could not be investigated employing mutagenesis. We also found that IL-6 activated two isoforms of STAT3 in Hep3B cells: STAT3α which contains both a DNA-binding domain and a transactivation domain and STAT3ß which contains only the DNA-binding domain. Taken together, these findings raise the possibility that IL-6 not only induces CRP expression but also regulates the induction of CRP expression by activating STAT3 isoforms and by utilizing all four STAT3 sites.

Plasma Interleukin-33 Cannot Predict Hip Osteonecrosis in Patients With Sickle Cell Disease: A Case-Control Study.

Background Plasma interleukin-33 (IL-33), a cytokine associated with inflammatory and autoimmune disease, has been described to be significantly raised in osteonecrosis of the femoral head (ONFH) and hence was recommended for use as a marker for ONFH. The concentration of plasma interleukin-33 level has not been estimated in any studies conducted in patients with sickle cell disease (SCD); hence, we investigated the levels of plasma interleukin-33 in patients with sickle cell disease with or without ONFH to assess whether it can be used as a marker for the early detection of ONFH in this disease also. Methods Forty-four consecutive patients with sickle cell disease with osteonecrosis of the femoral head and matched controls without ONFH were evaluated for plasma interleukin-33 levels by enzyme-linked immunosorbent assay (ELISA). All patients were confirmed for sickle cell disease using high-performance liquid chromatography (HPLC). ONFH was diagnosed in patients with sickle cell disease using clinical-radiological findings. Univariate and multivariate analyses were performed using the IL-33 level as the dependent variable. Results Plasma IL-33 levels were comparable in 44 patients with sickle cell disease with osteonecrosis of the femoral head as compared with 24 patients with sickle cell disease without ONFH (2.05 ± 4.57 pg/mL versus 1.50 ± 2.89 pg/mL, p-value = 0.590). There was no significant difference in IL-33 levels in different stages of avascular necrosis (AVN). Conclusions Plasma interleukin-33 levels cannot act as a marker of ONFH as were being considered in idiopathic ONFH or ONFH caused by other causes such as trauma and chronic steroid or alcohol usage.

Congenital Elbow Dislocation: A Case Report.

CASE: We present a case of a 12-day-old male baby who presented with right elbow deformity and inability to flex the elbow. Radiographs and computed tomography scan of the elbow revealed loss of humeroulnar alignment, superior migration of olecranon, and posteromedial displacement, suggesting an elbow dislocation. The child was successfully managed with open reduction and Kirschner wire fixation of the elbow joint. At 1-year follow-up, the child has a well-reduced and stable elbow joint with a functional range of movements. CONCLUSION: Congenital dislocation of the ulnohumeral joint can occur because of hypoplasia of the skeletal components or tissue interposition within the joint articulation.

Pathological Fractures of Bilateral Neck of Femur in Geriatric Population: Our Experience and Review of Literature.

Introduction: Bilateral neck of femur stress fractures is rare clinical presentation in elderly population. Diagnosis of such fractures when presented can be difficult with inconclusive radiographs and hence their early diagnosis by high index of suspicion and their management can avoid further complications in this age group. In this case series, we report three elderly patients with different predisposing factors for their fractures and treatment options chosen with detailed discussion about the management. Case Report: These case series of three elderly patients with bilateral neck of femur fracture were associated with different predisposing factors. Grave's disease or primary thyrotoxicosis, steroid induced osteoporosis, and renal osteodystrophy were the identified risk factors in these patients. Biochemical evaluation for osteoporosis in these patients revealed significant derangement in levels of vitamin D, Alkaline phosphatase, and serum calcium. One of these patients was operated with hemiarthroplasty and osteosynthesis with percutaneous screw fixation on the other side. Management of osteoporosis, dietary modifications, and lifestyle changes in these patients also had significant impact on their prognosis. Conclusion: Stress fractures occurring in elderly individuals with simultaneous bilateral presentation are rare and can be prevented if taken care on their risk factors. As radiographs remain inconclusive few times in these kinds of fracture, a high degree of suspicion is to be kept in mind. With advanced diagnostic tools and surgeries, they carry good prognosis if timely intervention is provided.

Usage of Accessory Anteromedial Portal for Anatomical Placement of Femoral Tunnel in Transportal Anterior Cruciate Ligament Reconstruction: A Prospective Study.

Background and objective The anterior cruciate ligament (ACL) has an essential role in preserving the function and stability of the knee joint. It acts primarily to prevent anterior tibial translation. Arthroscopic ACL reconstruction using quadrupled hamstring graft is the widely practiced modality for treating ACL injuries nowadays. The objective of this study was to assess the functional outcomes of ACL reconstruction using the transportal approach for a femoral tunnel through an accessory anteromedial portal (AAM). Materials and methods This prospective study included 35 patients who met the inclusion criteria. All patients underwent arthroscopic reconstruction of ACL using quadrupled hamstring tendon graft via transportal technique for femoral canal reaming through AAM. Patients were assessed for the functional outcome for a year using the Tegner-Lysholm knee scoring system. Results The analysis of the studied cases revealed that the mean age of the patients was around 27 years. Males were affected more than females. The left side (77.14%) was affected more than the right side (22.86%); 54.28% of patients had a history of road traffic accidents (RTAs). Preoperatively, 19 (54.28%) patients had poor and 16 (45.72%) patients had fair Tegner-Lysholm scores. After one year of follow-up, 29 (82.85%) of the patients had an excellent score as per the Tegner-Lysholm scoring system. Three patients had knee pain and thigh muscle wasting (2-3 cm), and two of them also had a sense of giving away during follow-up. Conclusion Anatomical reattachment of tendon graft for ACL reconstruction at femoral and tibial footprints is indispensable for good functional outcome and knee kinematics, and the usage of the AAM provides good visualization of femoral footprint and ease to surgeons during ACL reconstruction for making a near-accurate femoral tunnel and thereby achieving better outcomes.

Mammoth Giant Cell Tumor of the First Metacarpal: A Case Report and Management Trends.

Giant cell tumor (GCT) is classically described as a locally aggressive, epiphyseo-metaphyseal osteolytic tumor occurring in young adults. They are mostly seen in long bones while some are also found in the iliac bone and spine and a very small proportion occurs in hand bones. Due to the rarity of GCT in metacarpal, there is a paucity of treatment options available. In an extensive literature search on PubMed, Embase, Medline, and Ovid from 2004 till date, very few cases were reported. The various treatment options available are intralesional curettage with or without adjuvant therapy, wide resection, free osteoarticular metatarsal transfer, and, occasionally, ray amputation may also be done. After simple curettage, a reasonably high recurrence rate also imposes comprehensive en-bloc excision, but still, there are many case reports of recurrence. Experience with a case of GCT of the whole first metacarpal extending from the carpometacarpal to the metacarpophalangeal joint is not thoroughly described in the literature. We hereby report a mammoth GCT of the first metacarpal treated by excision and reconstruction by free fibular graft and adjacent joint fusion with an excellent functional outcome at one-year follow-up.

Giant Cell Tumor of the Distal Radius: Wide Resection, Ulna Translocation With Wrist Arthrodesis.

Giant cell tumor (GCT) of the bone is a locally aggressive neoplasm and usually managed with extended curettage and adjuvant therapy, which is associated with reduced risk of recurrence. The juxta-articular distal radius giant cell tumor is challenging due to the destruction of subchondral bone and articular cartilage, making it difficult to salvage the wrist joint anatomy and function. Various methods described include wide resection and reconstruction of allograft or centralization of the ulna with wrist arthrodesis. We present the functional outcome of distal end radius GCT, which was successfully managed with wide local excision, ulna translocation, and wrist arthrodesis. At the two years follow-up, the patient shows excellent functional outcome with supination and pronation movements and no local recurrence.

The Successful Management of a Repetitively Infected Recurrent Proximal Humerus Giant Cell Tumour of 20 Years' Duration With Two-Staged Surgery: A Rare Case Report.

The recurrence of giant cell tumour of bone (GCTB) is quite well known. It is mainly attributed to the presence of microscopic tumour remnants left behind after tumour treatment by intralesional curettage. This condition becomes more serious and alarming when the lesion gets infected postoperatively. Several studies have indicated that the role of adjuvants in preventing the recurrence of GCTs is limited, and complete removal of malignant cells is often mandatory. We present a rare case GCT of the proximal humerus in a female patient who developed repetitive recurrences of the tumour; her salvage procedures were also complicated by the development of infection after every treatment procedure for over 20 years. The patient was finally treated successfully with a two-stage revision and reconstruction procedure.

Congenital Posterior Dislocation of Fibula with Pes Valgus Deformity.

Congenital posterior dislocation of fibula with pes valgus deformity is a rare disorder in children and has not been reported in English literature. The parents recognize it when the child starts to bears weight as the foot appears normal non-weight bearing but on standing or bearing weight it goes into valgus. As the foot is manually correctable to neutral plaster correction does not suffice and surgery becomes essential. The differential diagnosis of this condition is the well-described congenital diastasis of inferior tibiofibular joint, where the foot is with equinovarus deformity. We are reporting a child of 2 years of age who presented to us walking on the medial border of sole, a valgus deformity on walking and no other congenital anomalies. We operated upon this case of congenital posterior dislocation of fibula with pes valgus deformity and are reporting it for the abnormal patho-anatomy, surgical steps followed and treatment protocol adopted by us.

Calcaneal Osteomyelitis Treated with Antibiotic Mixed Calcium Sulphate Pellets. A Case Report.

Background: Calcaneal osteomyelitis is a complicated entity and much more challenging to treat. We present a case of calcaneal osteomyelitis treated with debridement, curettage and filling bone defect with antibiotic mixed calcium sulphate pellets. Case Report: A female patient presented with pain, swelling and purulent discharge from the left heel. Culture studies and magnetic resonance imaging findings were suggestive of osteomyelitis of the calcaneum. The patient was planned for definitive treatment, and remission was achieved with systemic antibiotics, debridement, curettage, and filling dead space with antibiotic mixed calcium sulphate pellets. Conclusion: Calcaneal osteomyelitis is very resistant to treatment and results in poor functional outcome. Management of calcaneal osteomyelitis with single-stage strategy using antibiotic mixed calcium sulphate effectively eradicates the disease to attain overall good functional outcome for the patient.