Nanomedicine at the Pulmonary Frontier: Immune-Centric Approaches for Respiratory Disease Treatment.

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.

Advanced Overview of Biomarkers and Techniques for Early Diagnosis of Alzheimer's Disease.

The development of early non-invasive diagnosis methods and identification of novel biomarkers are necessary for managing Alzheimer's disease (AD) and facilitating effective prognosis and treatment. AD has multi-factorial nature and involves complex molecular mechanism, which causes neuronal degeneration. The primary challenges in early AD detection include patient heterogeneity and lack of precise diagnosis at the preclinical stage. Several cerebrospinal fluid (CSF) and blood biomarkers have been proposed to show excellent diagnosis ability by identifying tau pathology and cerebral amyloid beta (Aß) for AD. Intense research endeavors are being made to develop ultrasensitive detection techniques and find potent biomarkers for early AD diagnosis. To mitigate AD worldwide, understanding various CSF biomarkers, blood biomarkers, and techniques that can be used for early diagnosis is imperative. This review attempts to provide information regarding AD pathophysiology, genetic and non-genetic factors associated with AD, several potential blood and CSF biomarkers, like neurofilament light, neurogranin, Aß, and tau, along with biomarkers under development for AD detection. Besides, numerous techniques, such as neuroimaging, spectroscopic techniques, biosensors, and neuroproteomics, which are being explored to aid early AD detection, have been discussed. The insights thus gained would help in finding potential biomarkers and suitable techniques for the accurate diagnosis of early AD before cognitive dysfunction.

Quorum sensing inhibitors as Therapeutics: Bacterial biofilm inhibition.

The overuse and inappropriate use of antibiotics to treat bacterial infections has led to the development of multiple drug resistant strains. Biofilm is a complex microorganism aggregation defined by the presence of a dynamic, sticky, and protective extracellular matrix made of polysaccharides, proteins, and nucleic acids. The infectious diseases are caused by bacteria that flourish within quorum sensing (QS) mediated biofilms. Efforts to disrupt biofilms have enabled the identification of bioactive molecules produced by prokaryotes and eukaryotes. The QS system is quenched predominantly by these molecules. The phenomenon is also termed as quorum sensing (QS). Both synthetic and natural substances have been discovered to be useful in QS. This review describes natural and synthetic quorum sensing inhibitors (QSIs) with the potential to treat bacterial infections. It includes the discussion on quorum sensing, mechanism of quorum sensing, effect of substituents on the activity. These discoveries could result in effective therapies using far lower dosages of medications, particularly antibiotics, are currently needed.

Overexpression of gamma-glutamyl cyclotransferase 2;1 (CsGGCT2;1) reduces arsenic toxicity and accumulation in Camelina sativa (L.).

KEY MESSAGE: Overexpressing CsGGCT2;1 in Camelina enhances arsenic tolerance, reducing arsenic accumulation by 40-60%. Genetically modified Camelina can potentially thrive on contaminated lands and help safeguard food quality and sustainable food and biofuel production. Environmental arsenic contamination is a serious global issue that adversely affects human health and diminishes the quality of harvested produce. Glutathione (GSH) is known to bind and detoxify arsenic and other toxic metals. A steady level of GSH is maintained within cells via the γ-glutamyl cycle. The γ-glutamyl cyclotransferases (GGCTs) have previously been shown to be involved in GSH degradation and increased tolerance to toxic metals in plants. In this study, we characterized the GGCT2;1 homolog from Camelina sativa for its role in arsenic tolerance and accumulation. Overexpression of CsGGCT2;1 in Camelina under CaMV35S constitutive promoter resulted in strong tolerance to arsenite (AsIII). The overexpression (OE) lines had 2.6-3.5-fold higher shoots and sevenfold to tenfold enhanced root biomass on media supplemented with AsIII, relative to wild-type plants. The CsGGCT2;1 OE lines accumulated 40-60% less arsenic in root and shoot tissues compared to wild-type plants. Further, the OE lines had ~ twofold higher chlorophyll content and 35% lesser levels of malondialdehyde (MDA), an indicator of membrane damage via lipid peroxidation. There was a slight but non-significant increase in 5-oxoproline (5-OP), a product of GSH degradation, in OE lines. However, the transcript levels of Oxoprolinase 1 (OXP1) were upregulated, indicating the accelerated conversion of 5-OP to glutamate, which is further utilized for the resynthesis of GSH to maintain GSH homeostasis. Overall, this research suggests that genetically modified Camelina may have the potential for cultivation on contaminated marginal lands to reduce As accumulation; thereby could help in addressing food safety issues as well as future food and biofuel needs.

Quality by design-steered development and validation of analytical and bioanalytical methods for raloxifene: Application of Monte Carlo simulations and variance inflation factor.

A sensitive, rapid, reproducible, and economical HPLC method is reported for the quantification of raloxifene hydrochloride employing Quality by Design (QbD) principles. Factor screening studies, employing Taguchi design, indicated buffer volume percentage and isocratic flow rate as the critical method parameters (CMPs), which significantly influence the chosen critical analytical attributes, that is, tailing factor and theoretical plate number. Method conditions were subsequently optimized using face-centered cubic design with magnitude of variance inflation factor for assessing multicollinearity among CMPs. Method operable design region (MODR) was earmarked and liquid chromatographic separation optimized using 0.05 M citrate buffer, acetonitrile, and methanol (57:40:3 v/v/v) as ggmobile phase at 0.9 mL min-1 flow rate, λmax of 280 nm, and column temperature of 40°C. Validation of the developed analytical method was accomplished as per International Council on Harmonization (ICH) guidelines confirming high levels of linearity, precision, accuracy, robustness, and sensitivity. Application of Monte Carlo simulations enabled the attainment of best plausible chromatographic resolution and corroboration of the demarcated MODR. Establishment and validation of the bioanalytical method using rat plasma samples, along with forced degradation and stability studies, corroborated the aptness of developed HPLC methods for drug quantification in the biological fluids, as well as in bulk and marketed dosage forms.

A glass matrices-assisted quantum dots-based biosensor for selective capturing and detection of Escherichia coli.

Bacterial contamination of water and food is a grave health concern rendering humans quite vulnerable to disease(s), and proving, at times, fatal too. Exploration of the novel diagnostic tools is, accordingly, highly called for to ensure rapid detection of the pathogenic bacteria, particularly Escherichia coli. The current manuscript, accordingly, reports the use of silane-functionalized glass matrices and antibody-conjugated cadmium telluride (CdTe) quantum dots (QDs) for efficient detection of E. coli. Synthesis of QDs (size: 5.4-6.8 nm) using mercaptopropionic acid (MPA) stabilizer yielded stable photoluminescence (∼62%), corroborating superior fluorescent characteristics. A test sample, when added to antibody-conjugated matrices, followed by antibody-conjugated CdTe-MPA QDs, formed a pathogen-antibody QDs complex. The latter, during confocal microscopy, demonstrated rapid detection of the selectively captured pathogenic bacteria (10 microorganism cells/10 µL) with enhanced sensitivity and specificity. The work, overall, encompasses establishment and design of an innovative detection platform in microbial diagnostics for rapid capturing of pathogens in water and food samples.

Nanoscale Sulfur Improves Plant Growth and Reduces Arsenic Toxicity and Accumulation in Rice (Oryza sativa L.).

Rice is known to accumulate arsenic (As) in its grains, posing serious health concerns for billions of people globally. We studied the effect of nanoscale sulfur (NS) on rice seedlings and mature plants under As stress. NS application caused a 40% increase in seedling biomass and a 26% increase in seed yield of mature plants compared to untreated control plants. AsIII exposure caused severe toxicity to rice; however, coexposure of plants to AsIII and NS alleviated As toxicity, and growth was significantly improved. Rice seedlings treated with AsIII + NS produced 159 and 248% more shoot and root biomass, respectively, compared to plants exposed to AsIII alone. Further, AsIII + NS-treated seedlings accumulated 32 and 11% less As in root and shoot tissues, respectively, than the AsIII-alone treatment. Mature plants treated with AsIII + NS produced 76, 110, and 108% more dry shoot biomass, seed number, and seed yield, respectively, and accumulated 69, 38, 18, and 54% less total As in the root, shoot, flag leaves, and grains, respectively, compared to AsIII-alone-treated plants. A similar trend was observed in seedlings treated with AsV and NS. The ability of sulfur (S) to alleviate As toxicity and accumulation is clearly size dependent as NS could effectively reduce bioavailability and accumulation of As in rice via modulating the gene expression activity of As transport, S assimilatory, and glutathione synthesis pathways to facilitate AsIII detoxification. These results have significant environmental implications as NS application in agriculture has the potential to decrease As in the food chain and simultaneously enable crops to grow and produce higher yields on marginal and contaminated lands.

Global trends in pesticides: A looming threat and viable alternatives.

Pesticides are widely used chemical compounds in agriculture to destroy insects, pests and weeds. In modern era, they form an indispensable part of agricultural and health practices. Globally, nearly 3 billion kg of pesticides are used every year with a budget of ~40 billion USD. This extensive usage has increased the crop yield as well as led to significant reduction in harvest losses and thereby, enhanced food availability. On the other hand, indiscriminate usage of these chemicals has led to several environmental implications and caused adverse effects on human health. Epidemiological evidences have revealed the harmful effects of pesticides exposure on various organs including liver, brain, lungs and colon. Recent investigations have shown that pesticides can also lead to fatal consequences such as cancer among individuals. These chemicals enter ecosystem, thus hampering the sensitive environmental equilibrium through bio-accumulation. Due to their non-biodegradable nature, they can persist in nature for years and are regarded as potent biohazard. Worldwide, very few surveillance methods have been considered, which can bring awareness among the individuals, therefore the present review is an attempt to delineate consequences induced by various types of pesticide exposure on the environment. Further, the prospective of biopesticides use could facilitate the increase of crop production without compromising human health.

Impact of cyclodextrin derivatives on systemic release of duloxetine HCl via buccal route.

Aim: The aim of this work was to develop buccoadhesive tablets for the systemic delivery of duloxetine HCl (DXT) using more soluble derivatives of ß-cyclodextrin, i.e. hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD) and to investigate enhanced cellular uptake of inclusion complexed drug.Materials and methods: Freeze dried and spray dried complexes of both cyclodextrin derivatives with DXT (1:1 molar) were prepared and characterized with DSC, FTIR, and PXRD techniques. C971 and PC, on the basis of swelling behavior, erosion and in vitro residence time, were selected for further study at different levels (-1, 0, +1) to optimize the formulation in terms of enhanced drug release and ex vivo permeation.Results: SBEßCD based complexes show more aqueous solubility of DXT (0.782 and 0.958 mM) and more complexation efficiency compared to HPßCD at 25 °C and 37 °C, respectively. Apparent stability constant was reported to be higher (1109.94 and 1693.25 M-1) for DXT-SBEßCD at 25 °C and 37 °C, respectively, than the corresponding values for DXT-HPßCD systems. Enhanced cellular uptake using fibroblast cells was revealed for complexed drug compared to free drug .Conclusion: Both cyclodextrin derivatives are able to enhance drug release and permeation in vitro and ex vivo.

Screw Track Osteolysis in the Cementless Total Knee Replacement Design.

BACKGROUND: There is a paucity of reports on osteolysis associated with tibial screw fixation in cementless total knee arthroplasty (TKA), and the pathophysiology is not clear. This study aimed to describe the pathology related to screw track osteolysis around the tibia in cementless TKA. METHODS: The study cohort comprised 100 revised cementless TKAs with tibial screw fixation. Screw track osteolysis and various screw angles were analyzed radiologically. Tissue samples from the joint capsule and the osteolytic cavity were investigated for metal/polyethylene wear. The type of tissue response was determined using immunohistochemistry. Retrieved tibial polyethylene inserts were analyzed for screw hole impression and mode of wear. Tissue metal content was measured by inductively coupled plasma optical emission spectrometry. Electrochemical reactions between the tibial tray and the cancellous screws were investigated. RESULTS: Radiological analysis showed screw track osteolysis predominantly at the medial aspect of the tibial component, and the severity of osteolysis positively correlated with smaller medial proximal tibial screw angles. Osteolysis was associated with high titanium concentrations but not with polyethylene particles. An open circuit potential between the screw and the tibial base plate was measured. Necrosis, osteolytic cyst formation and macrophages, T and B cells, and dendritic cells were present. CONCLUSION: The present study highlights the risk for screw track osteolysis in cementless TKA with screw fixation. Our data collectively suggest that titanium wear may contribute to screw track osteolysis in the cementless TKA design. The contribution of screw angles is difficult to prove.

Present Scenario of Bioconjugates in Cancer Therapy: A Review.

Cancer is one of the deadliest diseases and poses a risk to people all over the world. Surgery, chemo, and radiation therapy have been the only options available until today to combat this major problem. Chemotherapeutic drugs have been used for treatment for more than 50 years. Unfortunately, these drugs have inherent cytotoxicities and tumor cells have started inducing resistance against these drugs. Other common techniques such as surgery and radiotherapy have their own drawbacks. Therefore, such techniques are incompetent tools to alleviate the disease efficiently without any adverse effects. This scenario has inspired researchers to develop alternative techniques with enhanced therapeutic effects and minimal side effects. Such techniques include targeted therapy, liposomal therapy, hormonal therapy, and immunotherapy, etc. However, these therapies are expensive and not effective enough. Furthermore, researchers have conjugated therapeutic agents or drugs with different molecules, delivery vectors, and/or imaging modalities to combat such problems and enhance the therapeutic effect. This conjugation technique has led to the development of bioconjugation therapy, in which at least one molecule is of biological origin. These bioconjugates are the new therapeutic strategies, having prospective synergistic antitumor effects and have potency to overcome the complications being produced by chemo drugs. Herein, we provide an overview of various bioconjugates developed so far, as well as their classification, characteristics, and targeting approach for cancer. Additionally, the most popular nanostructures based on their organic or inorganic origin (metallic, magnetic, polymeric nanoparticles, dendrimers, and silica nanoparticles) characterized as nanocarriers are also discussed. Moreover, we hope that this review will provide inspiration for researchers to develop better bioconjugates as therapeutic agents.

Basic concepts in metal work failure after metastatic spine tumour surgery.

PURPOSE: The development of spinal implants marks a watershed in the evolution of metastatic spine tumour surgery (MSTS), which has evolved from standalone decompressive laminectomy to instrumented stabilization and decompression with reconstruction when necessary. Fusion may not be feasible after MSTS due to poor quality of graft host bed along with adjunct chemotherapy and/or radiotherapy postoperatively. With an increase in the survival of patients with spinal tumours, there is a probability of an increase in the rate of implant failure. This review aims to help establish a clear understanding of implants/constructs used in MSTS and to highlight the fundamental biomechanics of implant/construct failures. METHODS: Published literature on implant failure after spine surgery and MSTS has been reviewed. The evolution of spinal implants and their role in MSTS has been briefly described. The review defines implant/construct failures using radiological parameters that are practical, feasible, and derived from historical descriptions. We have discussed common modes of implant/construct failure after MSTS to allow further understanding, interception, and prevention of catastrophic failure. RESULTS: Implant failure rates in MSTS are in the range of 2-8%. Variability in patterns of failure has been observed based on anatomical region and the type of constructs used. Patients with construct/implant failures may or may not be symptomatic and present either as early (< 3months) or late failures (> 3months). It has been noted that not all the implant failures after MSTS result in revisions. CONCLUSION: Based on the observed radiological criteria and clinical presentations, we have proposed a clinico-radiological classification for implant/construct failure after MSTS.

What Is the Role of Diagnostic and Therapeutic Sonication in Periprosthetic Joint Infections?

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most dreaded complications in joint replacement surgery. Diagnosis and treatment can be difficult and biofilms are of major concern due to their low susceptibility toward antibiotics. METHODS: This review focuses on the use of sonication as an evolving diagnostic and adjunct treatment modality in the context of PJI. Therapeutic application of sonication is discussed separately for its (i) direct action on bacteria, (ii) synergistic effects with antibiotics, and (iii) effects on release of antibiotics from bone cement. RESULTS: Used as a diagnostic tool, sonication shows promising results with respect to sensitivity and specificity when compared to conventional methods, notably after previous administration of antibiotics. As an adjunct treatment modality, the chemical, physical, and mechanical effects of sonication are primarily driven by cavitation and recognized as the main cause for bactericidal effects but the exact underlying mechanisms have not been identified yet. Sonication alone does not have the ability to completely eradicate biofilms but synergistic effects when used in conjunction with antibiotics have been reported. There is also evidence for enhanced antibiotic release from bone cement. CONCLUSION: Sonication is as an evolving modality in the context of PJIs. As a diagnostic tool, it has not been introduced in routine clinical practice and sonication as a treatment modality in PJIs is still in an experimental stage. Factors such as frequency, pressure, chemical activity, intensity, and exposure time need to be evaluated for optimal application of sonication and may also improve study comparison.

Cancer Cell Targeting Using Folic Acid/Anti-HER2 Antibody Conjugated Fluorescent CdSe/CdS/ZnS-Mercaptopropionic Acid and CdTe-Mercaptosuccinic Acid Quantum Dots.

CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.

Intraoperative cell salvage in metastatic spine tumour surgery reduces potential for reinfusion of viable cancer cells.

PURPOSE: This study aimed at evaluating our hypothesis that tumour cells, which pass through the intraoperative cell salvage (IOCS) machine, lose viability due to possible injury to the cell membrane during centrifugation and filtration, enabling safe reinfusion even without filtration. METHODS: Thirteen patients who underwent metastatic spine tumour surgery (MSTS) at our institution were recruited. Blood samples (5 ml each) were collected at five different stages during surgery, namely, stage A and B: from patients' vein during induction and at the time of maximum tumour manipulation; stage C, D and E: from the operative blood prior to IOCS processing, after IOCS processing and after IOCS-LDF (leucocyte depletion filter) processing, respectively. The samples were then analysed for viability of tumour cells using microwell-based culture. RESULTS: The median age of the patients was 65 years (range 37-77 years). The most common primary tumour was lung, followed by breast, hepatocellular and renal cell carcinoma. The median blood loss was 680 ml (range 300-1500 ml). Analysis of cultured blood samples showed that CTC-containing clusters were developed from some samples before IOCS-LDF processing (stage A: three patients, stage B: three patients and stage C: one patient). None of the samples from stages D and E generated clusters after culture, suggesting the absence of viable cancer cells after IOCS processing. CONCLUSIONS: The salvaged blood may contain some tumour cells after processing with IOCS machine, but these cells are damaged and hence unable to replicate and unlikely to metastasise. The results of this study support the hypothesis that salvaged blood in MSTS is safe for transfusion.

Ballooning osteolysis in 71 failed total ankle arthroplasties.

Background and purpose - Aseptic loosening is a major cause of failure in total ankle arthroplasty (TAA). In contrast to other total joint replacements, large periarticular cysts (ballooning osteolysis) have frequently been observed in this context. We investigated periprosthetic tissue responses in failed TAA, and performed an element analysis of retrieved tissues in failed TAA. Patients and methods - The study cohort consisted of 71 patients undergoing revision surgery for failed TAA, all with hydroxyapatite-coated implants. In addition, 5 patients undergoing primary TAA served as a control group. Radiologically, patients were classified into those with ballooning osteolysis and those without, according to defined criteria. Histomorphometric, immunohistochemical, and elemental analysis of tissues was performed. Von Kossa staining and digital microscopy was performed on all tissue samples. Results - Patients without ballooning osteolysis showed a generally higher expression of lymphocytes, and CD3+, CD11c+, CD20+, and CD68+ cells in a perivascular distribution, compared to diffuse expression. The odds of having ballooning osteolysis was 300 times higher in patients with calcium content >0.5 mg/g in periprosthetic tissue than in patients with calcium content ≤0.5 mg/g (p < 0.001). Interpretation - There have been very few studies investigating the pathomechanisms of failed TAA and the cause-effect nature of ballooning osteolysis in this context. Our data suggest that the hydroxyapatite coating of the implant may be a contributory factor.

Cancer Cell Targeting Using Folic Acid/Anti-HER2 Antibody Conjugated Fluorescent CdSe/CdS/ZnS-MPA and CdTe-MSA Quantum Dots.

CdSe/CdS/ZnS and CdTe quantum dots (QDs) were synthesized by successive ion layer adsorption and reaction (SILAR) technique and direct aqueous synthesis respectively using thiol stabilizers. Synthesized CdSe/CdS/ZnS and CdTe QDs stabilized with 3-mercaptopropionic acid (MPA) and mercaptosuccinic acid (MSA) were used as fluorescent labels after conjugation with folic acid (FA) and anti-HER2 antibodies. Photoluminescence quantum yield of folated CdSe/CdS/ZnS-MPA and CdTe-MSA QDs was 59% and 77% than that of non-folated hydrophilic QDs. The folate receptor-mediated delivery of folic acid-conjugated CdTe-MSA and CdSe/CdS/ZnS-MPA QDs showed higher cellular internalization as observed by confocal laser scanning microscopic studies. Folated and non-folated CdTe-MSA QDs were highly toxic and exhibited only 10% cell viability as compared to > 80% cell viability with CdSe/CdS/ZnS-MPA QDs over the concentration ranging from 3.38 to 50 pmoles. Immunohistochemistry (IHC) results of human breast cancer tissue samples showed positive results with anti-HER2 antibody conjugated CdSe/CdS/ZnS-MPA QDs with better sensitivity and specificity as compared to conventional IHC analysis using diaminobenzedene staining.

Stump lengthening procedure with modular endoprostheses - the better alternative to disarticulations of the hip joint?

We report outcomes of 28 patients after stump-lengthening procedures (SLPs) with modular tumor endoprostheses following high-thigh amputation and hip disarticulation over 11years. Mean follow up was 41.3months (range 7.4 to 133.6months). Mean Musculoskeletal Tumour Society Score was 56% (n=11); ten out of eleven patients alive used an exoprosthesis regularly. Complications occurred in 15 patients with infection being most common. In 2 cases, the prostheses had to be explanted. Our data suggest that SLP facilitates post-operative rehabilitation and prosthesis usage. Modular endoprostheses for stump-lengthening allow optimization of remnant soft-tissue envelope, reducing the risk of stump perforation.

Modular tumor endoprostheses in surgical palliation of long-bone metastases: a reduction in tumor burden and a durable reconstruction.

BACKGROUND: Surgical treatment of bone metastases has become increasingly important as patients live longer with metastatic cancer and one of the main aims is a long-lasting reconstruction which survives the patient. Conventional osteosynthesis may not be able to achieve this objective in the context of modern day cancer care. METHODS: This study evaluates the oncological outcomes, treatment-related complications, and function after resection of metastases and reconstruction with modular tumor endoprostheses in 80 patients. All patients who underwent surgical treatment with modular tumor prostheses for bone metastases from 1993 to 2008 were traced by our tumor database and clinical information was recorded from patient case. RESULTS: Mean age was 63 years. The most common primary tumors were renal cell (47%), breast (21%), and lung (8%). The proximal femur was affected in 45%, proximal humerus in 26%, and the distal femur in 17% of cases. In 22 cases, the tumor prosthesis was implanted during a revision operation. Mean overall survival after surgery was 2.9 years. Overall survival rate was 70% at one year and 20% at five years. Implant survival was 83% after one year and 74% at five years. Overall rate of operative revision was 18%. CONCLUSIONS: Our data collectively suggest that despite higher costs, implantation of modular tumor endoprostheses may be a suitable treatment for bone metastases with a low complication rate and rapid improvement in function in appropriately selected patients.

Ceramic femoral component fracture in total knee arthroplasty: an analysis using fractography, fourier-transform infrared microscopy, contact radiography and histology.

Ceramic components in total knee arthroplasty (TKA) are evolving. We analyze the first case of BIOLOX delta ceramic femoral component fracture. A longitudinal midline fracture in the patellar groove was present, with an intact cement mantle and no bony defects. Fractographic analysis with laser scanning microscopy and white light interferometry showed no evidence of arrest lines, hackles, wake hackles, material flaws, fatigue or crack propagation. Analysis of periprosthetic tissues with Fourier-transform infrared (FT-IR) microscopy, contact radiography, histology, and subsequent digestion and high-speed centrifugation did not show ceramic debris. A macrophage-dominated response was present around polyethylene debris. We conclude that ceramic femoral component failure in this case was related to a traumatic event. Further research is needed to determine the suitability of ceramic components in TKA.