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.

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.

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.

Distal Femur Tumor Megaprosthesis for Non-union of Supracondylar Femur Fracture after Failed Osteosynthesis. An Ingenious Solution.

Introduction: Incidence of non-union of fracture involving the supracondylar region of femur in an elderly is increasing due to bone loss from trauma and availability of poor quality bone in geriatric population. Distal femur megaprosthesis can provide a single stage solution for resistant non-union of supracondylar femur. Case Report: We are reporting two cases of non-union of supracondylar femur with implant failure treated with distal femoral tumor megaprosthesis. We achieved excellent improvement of the Knee Society Score from 15 to 75; Knee Society Function Score from 0 to 60, good range of motion, and pain free ambulation without support at 3 months follow-up. Conclusion: Management of non-union of supracondylar femur with implant failure is challenging task. Distal femur replacement using tumor megaprosthesis is useful option for such resistant cases in achieving early ambulation and overall good functional outcome.

Outcomes of Tumor Resection and Reconstruction by Megaprosthesis around Knee: Our Experience.

Introduction: In this modern era, limb reconstructive surgeries have become a standardized procedure for malignant tumor of lower limbs. We performed limb salvage surgeries for tumor around the knee with en bloc resection and subsequent reconstruction with a megaprosthesis. Methods: A total of six cases of malignant and locally aggressive tumor around the knee were operated on from 2017 to 2018, with resection and mega prosthetic reconstruction. Interpretation of functional outcome after surgery was performed with musculoskeletal tumor society (MSTS) score. Complications such as infection, local recurrence of tumor, implant failure, and distant metastases were evaluated during each follow-up. Results: Postoperatively, one patient developed superficial infection; one local recurrence with metastasis and the rest cases were uneventful. Patients were regularly followed for atleast1 year, and none of them developed any sign of deep infection, implant failure,or loosening. At the beginning of treatment, the average MSTS score was 8.83, which showed a significant increment to 25.83 after 12 months of follow-up. Conclusion: Albeit few cases were operated on, we draw this inference from our short-term experience that mega prosthesis acts as a boon to orthopedic surgeons in musculoskeletal tumor management, thereby uplifting the quality of life of patients even during terminal care.

Giant Ewing's Sarcoma of the Body of the Scapula.

INTRODUCTION: Ewing sarcoma is a malignant neoplasm occurring usually in bones such as femur, tibia, and iliac wing. We are here reporting a case of same arising from scapula. Of all the tumors arising from scapula, Ewing's sarcoma contributed to only 8%. CASE REPORT: A male patient presented to us with pain and swelling over right scapular region. After initial investigation, biopsy was performed. Biopsy reveals uniform small-sized cells arranged in layers with high nucleus to cytoplasmic ratio. Provisional diagnosis of Ewing sarcoma was made which was later confirmed on immunohistochemistry. The patient underwent planned surgery after neoadjuvant chemotherapy, and swelling along with partial scapula was resected. CONCLUSION: Although Ewing sarcoma is common neoplasm, it rarely arises from flat bone-like scapula. Henceforth, reporting of such a case is not only imperative but also mandatory.

Estimating the size of substance using street children in Delhi using Respondent-Driven Sampling (RDS).

Street children as a population sub-group exist in significant numbers in the developing world and have been reported to be vulnerable to adverse health and risk behaviours that include physical and sexual risk behaviour. However, the estimation of prevalence for various psychoactive substances among the street children in a representative sample has not been attempted in the developing country like India. This is challenging due to the absence of an appropriate sampling frame, the population living in isolation, hiding their identity and concealing their behaviour. Use of psychoactive substances in street children is riddled with these challenges. The present investigation describes the findings from size estimation study on a representative sample of street child (n = 766) in Delhi, by implementing the Respondent Driven Sampling Methodology (RDS). The weighted prevalence for three commonest substances was found as Tobacco (31.1 %), alcohol (13.5 %) and inhalants (11.3 %) used during the last one year with the estimated number as -Tobacco (21,770), Alcohol (9450) and Inhalants (5600). Almost one third of street children were using some substance. Also, a large majority of ever users were also using substances currently. The study demonstrates successfully the implementation of RDS for the estimation of the prevalence of psychoactive substances in a representative manner. A large majority of street children use psychoactive substances, and there is a need for more of such studies in other metropolitan cities so that local level interventions and planning can be done for treatment and prevention of psychoactive substances among the street children. The important public health implications had been discussed.

Does Cannabis Use Influence Opioid Outcomes and Quality of Life Among Buprenorphine Maintained Patients? A Cross-sectional, Comparative Study.

OBJECTIVES: Use of various psychoactive substances can influence outcomes of patients on opioid agonist treatment (OAT). While use of alcohol and cocaine has shown to adversely affect OAT results, associated cannabis use shows mixed results. This study aimed to assess the pattern of cannabis use among opioid-dependent patients maintained on buprenorphine. Additionally, the study compared the dose of buprenorphine, opioid-related craving and withdrawals, productivity, and also quality of life between those with and without recent (past 90-day) cannabis use. METHODS: We collected data on demographic and drug use details in 100 randomly selected adult male patients attending a community drug treatment clinic, who were stabilized on buprenorphine for more than 3 months. Other measures included scores on World Health Organization (WHO)-Alcohol, Smoking and Substance Involvement Screening Tool and WHO-Quality of Life-Brief (WHOQOL-Bref) version. RESULTS: The average duration of maintenance treatment with buprenorphine was 96 months, with excellent compliance for buprenorphine (86.92 ±â€Š9.58 days in 90 days). Thirty-five per cent had used cannabis in past 90 days, with lifetime use of cannabis in 77%. Participants using cannabis currently were on lower doses of buprenorphine (mean dose per day: 7.9 mg vs 8.9 mg; P = 0.04). Yet, there was no significant difference in the rates of opioid use or opioid withdrawals and craving between the 2 groups. Compliance to OAT, number of days of employment, daily earning, and WHOQOL-Bref scores in all domains were comparable between those with and without cannabis use. Duration of cannabis use, current use of alcohol, and dose of buprenorphine predicted current cannabis use in multivariable logistic regression analysis. CONCLUSIONS: Cannabis use does not negatively influence opioid outcomes among patients receiving buprenorphine maintenance treatment. There is no difference in productivity and quality of life between individuals maintained on buprenorphine with and without current cannabis use.

Fat Embolism Syndrome in Fracture Tibia Treated By Unreamed Interlocking Nail.

Incidence of Fat embolism syndrome (FES) in fractures is about 16.3 but sometimes it is as high as 50% to 62%. The fat embolism is common in fatty bed ridden patients and in whom reamed interlocking is performed under tourniquet with prolonged injury-surgery interval. However in the case discussed here FES occurred under the exact opposite circumstances. In this 23 year lean and thin female with closed tibia fracture unreamed interlocking was performed without tourniquet & the operative procedure was done within 4 hours after trauma. Her pre-operative investigation were within normal limit. We want to discuss by this case report to highlight that even when risk factors are absent outlier events of FES can occur in any case and symptoms should not be discounted.

Oct-1 acts as a transcriptional repressor on the C-reactive protein promoter.

C-reactive protein (CRP), a plasma protein of the innate immune system, is produced by hepatocytes. A critical regulatory region (-42 to -57) on the CRP promoter contains binding site for the IL-6-activated transcription factor C/EBPß. The IL-1ß-activated transcription factor NF-κB binds to a κB site located nearby (-63 to -74). The κB site overlaps an octamer motif (-59 to -66) which is the binding site for the constitutively active transcription factor Oct-1. Oct-1 is known to function both as a transcriptional repressor and as an activator depending upon the promoter context. Also, Oct-1 can regulate gene expression either by binding directly to the promoter or by interacting with other transcription factors bound to the promoter. The aim of this study was to investigate the functions of Oct-1 in regulating CRP expression. In luciferase transactivation assays, overexpressed Oct-1 inhibited (IL-6+IL-1ß)-induced CRP expression in Hep3B cells. Deletion of the Oct-1 site from the promoter drastically reduced the cytokine response because the κB site was altered as a consequence of deleting the Oct-1 site. Surprisingly, overexpressed Oct-1 inhibited the residual (IL-6+IL-1ß)-induced CRP expression through the promoter lacking the Oct-1 site. Similarly, deletion of the Oct-1 site reduced the induction of CRP expression in response to overexpressed C/EBPß, and overexpressed Oct-1 inhibited C/EBPß-induced CRP expression through the promoter lacking the Oct-1 site. We conclude that Oct-1 acts as a transcriptional repressor of CRP expression and it does so by occupying its cognate site on the promoter and also via other transcription factors by an as yet undefined mechanism.

Correlation between MRI appearances and serum alkaline phosphatase levels in Osteogenic sarcoma.

INTRODUCTION: Magnetic resonance imaging is a pictorial depiction of the patho-anatomy of a bony lesion. As different parts of the tumor in Osteogenic sarcoma concurrently undergo various biological processes i.e. osteoblastic new bone formation, cell death, necrosis, bony destruction and revascularization etc., we hypothesized that the image seen in MRI could be used to assess the tumor behavior at that time. This study was done as a preliminary study with the aim to find whether the MRI pictures can have identifiable patterns and if present whether they can be linked to biological behavior. We could identify 2 distinct patterns in T2 weighted images which correlated well with serum alkaline phosphatase a serum marker and the duration of symptoms and so we are reporting our observations. MATERIAL AND METHOD: T2 weighted MRI pictures of 15 cases of Osteogenic sarcoma were studied for identifiable patterns in matrix. These patterns if found were to be linked to biological behavior in the form of serum alkaline phosphatase levels and duration of symptoms. RESULTS: We could identify 2 unique patterns named by us as Group 1 Heterogeneous type (4 cases) which had a raised serum alkaline phosphatase level and had a history at presentation of less than 3 months duration. In Group 2 homogenous type (5 cases) the serum alkaline phosphatase levels were low and the cases presented after 6 months. As we could not identify any logical pattern in rest of the cases we labeled them as miscellaneous. DISCUSSION: MRI patterns can be used as markers of disease activity as there are 2 clear poles correlating well with serum alkaline phosphatase levels (high or low). Intermediate patterns may be the natural biological behavior and waxing and waning of the tumor disease activity.

Pattern recognition by pentraxins.

Pentraxins are a family of evolutionarily conserved pattern-recognition proteins that are made up of five identical subunits. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver while PTX3 is produced in a variety of tissues during inflammation. The main functions of short pentraxins are to recognize a variety of pathogenic agents and then to either eliminate them or neutralize their harmful effects by utilizing the complement pathways and macrophages in the host. CRP binds to modified low-density lipoproteins, bacterial polysaccharides, apoptotic cells, and nuclear materials. By virtue of these recognition functions, CRP participates in the resolution of cardiovascular, infectious, and autoimmune diseases. SAP recognizes carbohydrates, nuclear substances, and amyloid fibrils and thus participates in the resolution of infectious diseases, autoimmunity, and amyloidosis. PTX3 interacts with several ligands, including growth factors, extracellular matrix component and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes. In addition, data in gene-targeted mice show that PTX3 is essential in female fertility, participating in the assembly of the cumulus oophorus extracellular matrix. PTX3 is therefore a nonredundant component of the humoral arm of innate immunity as well as a tuner of inflammation. Thus, in conjunction with the other components of innate immunity, the pentraxins use their pattern-recognition property for the benefit of the host.