How Do Metal Ion Levels Change over Time in Hip Resurfacing Patients? A Cohort Study

Metal-on-metal hip resurfacing (MOM-HR) is offered as an alternative to traditional hip arthroplasty for young, active adults with advanced osteoarthritis. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting increase in metal ion levels. We evaluated three cohorts of patients with Birmingham hip resurfacing (BHR) at an average follow-up of 2, 5, and 9 years. We asked whether there would be differences in ion levels between the cohorts and inside the gender. Nineteen patients were prospectively analyzed. The correlation with clinical-radiographic data was also performed. Chromium, cobalt, nickel, and molybdenum concentrations were measured by atomic absorption spectrophotometry. Chromium and cobalt levels demonstrated a tendency to decrease over time. Such tendency was present only in females. An inverse correlation between chromium, implant size, and Harris hip score was present at short term; it disappeared over time together with the decreased ion levels. The prospective analysis showed that, although metal ion levels remained fairly constant within each patient, there was a relatively large variation between subjects, so mean data in this scenario must be interpreted with caution. The chronic high exposure should be carefully considered during implant selection, particularly in young subjects, and a stricter monitoring is mandatory

Blocking Tumor-Educated MSC Paracrine Activity Halts Osteosarcoma Progression

Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets.Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography.Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGF\u3b2, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGF\u3b2-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGF\u3b2 are increased in osteosarcoma patients.Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGF\u3b2-blocking agents as new therapeutic options for osteosarcoma patients. Clin Cancer Res; 23(14); 3721-33. \ua92017 AACR

Effect of acetabular cup design on metal ion release in two designs of metal-on-metal hip resurfacing

The purpose of this observational prospective cohort study was to evaluate the serum concentrations of cobalt (Co), chromium (Cr), and nickel (Ni) at a 2-year followup in patients operated on with a novel design of hip resurfacing: Romax resurfacing system (RRS). RRS is characterized by the presence of an acetabular notch which theoretically provides a wider range of motion and a reduced incidence of groin pain. The presence of radiolucencies and functional outcome, assessed using the Harris hip score (HHS) and the University of California Activity scale (UCLA), were secondary endpoints. Moreover, these results were compared with those obtained in our previous study from a similar cohort of patients implanted using the Birmingham Hip Resurfacing (BHR) system. At a 2-year follow-up, the serum levels of Co in patients operated on using the RRS were five times higher (p50.0002) than those found before surgery (Co, means: 1.04 and 0.20 ng/mL, respectively); similarly, Cr levels were 13 times higher (p<0.0001) at a 2-year follow-up than before surgery (Cr, means: 1.69 and 0.13 ng/mL, respectively). Ni concentrations (0.42 and 0.78 ng/mL) were not significantly different (p50.16), even if they increased 86% after surgery. In the RRS patients, an inverse correlation was found between Co and Cr concentrations and length of follow-up (Co: r520.64, p50.0096; Cr: r5 20.45, p50.08). The serum levels of Co and Cr were not significantly different between RRS (Co: 1.04 ng/mL and Cr: 1.69 ng/mL) and BHR (Co: 1.39 ng/mL and Cr: 2.30 ng/mL) patients at 2 years (p50.95 and 0.26 for Co and Cr, respectively). Our results showed that RRS patients achieved an excellent clinical outcome with limited metal ion release

Fetal sex identification in maternal plasma by means of short tandem repeats on chromosome X

Analysis of fetal DNA in maternal plasma has recently been introduced as a new method for noninvasive prenatal diagnosis. In the majority of cases, the Y chromosome-specific sequences are commonly used as a fetus-specific marker with a high risk of false-negative cases. We attempted to develop a sensitive and reliable X chromosome short tandem repeat (STR) multiplex PCR amplification system that is suitable for the amplification of short-sized templates of free fetal DNA. Because of specific characteristics of fetal DNA in maternal plasma, cell-free fetal DNA is smaller than corresponding maternal DNA, and so we selected 10 X-STR loci in which the allele size was 250 bp. In addition, fetal sex was also investigated using the amelogenin gene in the same multiplex assay. Twenty-six women were enrolled in the study. Eight of 26 total fetuses analyzed were male and 18 were female. In the whole sample, X-STRs were informative with a mean of 4.84 ± 1.43. A mean of 2.67 ± 1.28 X-STR markers per sample (range 1-5) of paternally inherited fetal alleles were detected in pregnant women carrying a female fetus. In all cases, blind determination of fetal sex by means of the identification of amelogenin and X-STR markers was confirmed by fetal karyotyping. This study showed that this noninvasive technique is a reliable and accurate tool to investigate free fetal DNA in pregnancies within the first trimester and could be widely used in clinical research and diagnosis. © 2008 New York Academy of Sciences

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique

Long-Term Follow-Up of Elderly Patients with Acute Myeloid Leukemia Treated with Decitabine: A Real-World Study of the Apulian Hematological Network

Decitabine, a DNA hypomethylating agent, was approved for use in adults with acute myeloid leukemia (AML) not eligible for standard chemotherapy and is now widely accepted as standard treatment. Although a number of clinical trials demonstrated its benefits in elderly AML patients, older adults and patients with frequent comorbidities are typically under-represented in such settings. Thus, the aim of the present study is to evaluate, in a real-world setting, the effectiveness and toxicity of decitabine administered as a single agent in unselected previously untreated elderly AML patients not eligible for intensive chemotherapy. In nine hematological departments of the Apulian Hematological Network (REP), we enrolled 199 patients (median age: 75.4 years; range: 61&ndash;91) with de novo (n = 94) or secondary/therapy-related (n = 105) AML treated with decitabine 20 mg/m2 for five days every 4 weeks. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using multivariate Cox regression. The average number of cycles administered per patient was 6.3 (SD: 6.0; median: 5 cycles). Complete response was achieved by 31 patients (15.6%) and partial response by 57 (28.6%), for a total of 88 responders overall (44.2%). After a median follow-up of 33.6 months, median OS was 8.7 months (95% CI: 7.4&ndash;10.3), and the 6-month, 1-year, and 3-year OS rates were 62.7%, 37.0%, and 7.1%, respectively. Mortality was increased in AML patients with &ge;3 comorbidities (HR = 2.45; 95% CI: 1.18&ndash;5.08) vs. no comorbidities and in those with adverse karyotype (HR = 1.58; 95% CI: 1.05&ndash;2.38) vs. favourable or intermediate profile. Infection was the main registered adverse event (46.0%). In conclusion, this REP real-life study demonstrates, after a follow-up of almost 3 years, how decitabine administered to AML patients not suitable for intensive chemotherapy is effective and well tolerated, even in a population of truly elderly patients with frequent comorbidities