Multiple or metastatic clear cell chondrosarcoma: a case report

We report multiple synchronous clear-cell chondrosarcomas in a 43-year-old patient. The patient had a lesion in the right proximal humerus and in the left femoral condyle. Bone scintigraphy revealed increased uptake in both foci. Pathological analysis confirmed the diagnosis in both locations. In the proximal humerus, wide resection of the tumour was performed with allograft reconstruction of the joint with osteosynthesis. The femoral condyle was treated with curettage, phenolization, and cementation. Over a follow-up of 10 years no recurrence or metastasis was observed

HUMAN MESENCHYMAL STEM CELLS AS A MODEL OF STUDY FOR NEW BIOMATERIALS IN BONE TISSUE REGENERATION

The reconstruction of large bone segments remains a critical clinical problem in the case of extensive bone loss due to traumatic or pathological events. Due to its ideal biocompatibility and osteogenic properties, autologous bone is still considered the gold standard for bone replacement applications, however its use has limitations such as supply amount and unpredictable healing kinetics. These limitations and recent progress in biotechnology have driven the development of materials/scaffolds for bone repair. Biocompatibility issues and materials/scaffolds features need to be investigated and the usefulness of human cell cultures for biocompatibility testing is confirmed by experimental studies. In-vitro models employing human cells to study the interactions between the cell system and the biomaterial/device allow for a reasonable prediction of its performance in vivo. To study coral derived Hydroxyl-Apatite (HA) osteo-conductivity and cyto-toxicity we employed an engineered osteoblast-like cellular model named Saos-eGFP. Although the efficacy of this cellular model, the need of an in-vitro tool resembling a more physiological-like cellular response, led to the development of an adult human mesenchymal stem cell (hMSCs) model. This model was employed to assay porous stoichiometric HA and non-stoichiometric Mg-HA bone substitutes. Our studies showed how human cells may be employed to analyze osteo- conductivity/inductivity and cyto-toxicity, and specifically how hMSCs allow a more insightful understanding of the earliest phase of cell-biomaterial interaction, addressing the question of which type of biomaterials could be better for bone regeneration applications

Serum IgG antibodies from pregnant women reacting to mimotopes of simian virus 40 large T antigen, the viral oncoprotein

Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected from pregnant and non-pregnant women, with the same mean age. Women were in the range of 15-48 years old. Samples were assayed by an indirect ELISA employing specific SV40 LT mimotopes as antigens, whereas functional analysis was performed by neutralization of the viral infectivity in cell cultures. As a control, sera were analyzed for Ab against BK polyomavirus (BKPyV), which is a human polyomavirus homologous to SV40. Statistical analyses employed chi-square with Yates' correction, and Student's t tests. Indirect ELISAs indicated that pregnant women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non-pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were detected with a prevalence of 80% in pregnant women and with a prevalence of 78% in non-pregnant women. These data indicate that SV40 infects at a low prevalence pregnant women. We may speculate that SV40, or a close human polyomavirus still undetected, could be transmitted from mother to fetus

Optimized pipeline of MuTect and GATK tools to improve the detection of somatic single nucleotide polymorphisms in whole- exome sequencing data

Background: Detecting somatic mutations in whole exome sequencing data of cancer samples has become a popular approach for profiling cancer development, progression and chemotherapy resistance. Several studies have proposed software packages, filters and parametrizations. However, many research groups reported low concordance among different methods. We aimed to develop a pipeline which detects a wide range of single nucleotide mutations with high validation rates. We combined two standard tools – Genome Analysis Toolkit (GATK) and MuTect – to create the GATK-LODN method. As proof of principle, we applied our pipeline to exome sequencing data of hematological (Acute Myeloid and Acute Lymphoblastic Leukemias) and solid (Gastrointestinal Stromal Tumor and Lung Adenocarcinoma) tumors. We performed experiments on simulated data to test the sensitivity and specificity of our pipeline. Results: The software MuTect presented the highest validation rate (90 %) for mutation detection, but limited number of somatic mutations detected. The GATK detected a high number of mutations but with low specificity. The GATK-LODN increased the performance of the GATK variant detection (from 5 of 14 to 3 of 4 confirmed variants), while preserving mutations not detected by MuTect. However, GATK-LODN filtered more variants in the hematological samples than in the solid tumors. Experiments in simulated data demonstrated that GATK-LODN increased both specificity and sensitivity of GATK results. Conclusion: We presented a pipeline that detects a wide range of somatic single nucleotide variants, with good validation rates, from exome sequencing data of cancer samples. We also showed the advantage of combining standard algorithms to create the GATK-LODN method, that increased specificity and sensitivity of GATK results. This pipeline can be helpful in discovery studies aimed to profile the somatic mutational landscape of cancer genomes

Erratum to: Orally administered multispecies probiotic formulations to prevent uro-genital infections: a randomized placebo-controlled pilot study

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Lengthening Patients Previously Treated for Massive Lower Limb Reconstruction for Bone Tumors with the PRECICE 2 Nail

The objective of this study was to determine the efficacy of the PRECICE 2 (R) nail in the treatment of lower limb length discrepancy in patients with a history of bone tumors. This study reports on outcomes, complications, and the safety of the PRECICE 2 limb lengthening nail in a cohort of pediatric patients with limb length discrepancy after surgery for bone tumors. Seventeen patients were treated with intramedullary magnetic nails. The average patient age at the time of surgery was 19 (range 11-32). The PRECICE 2 nail was used on 14 femurs (6 retrograde and 8 anterograde) and 3 tibias. The average consolidation time was 141 days (range 50-360) with a mean CI of 31 +/- 12 days/cm. The ASAMI bone score showed 14 (82%) excellent results, 1 (6%) good result, and 2 (12%) poor results. The ASAMI functional score showed 13 (84.6%) excellent results, 3 (11.5%) good results, and 1 (3.8%) fair result. Patients treated with chemotherapy for bone cancer did not show any increase in distraction time or consolidation time. A total of 3 (17%) problems, 1 obstacle (5.5%), and 1 complication (5.5%) were encountered in our case series. The PRECICE 2 nail allows for effective and accurate lengthening preserving the range of motion in patients treated for bone tumors

Psychological Well-Being, Self-Esteem, Quality of Life and Gender Differences as Determinants of Post-Traumatic Growth in Long-Term Knee Rotationplasty Survivors: A Cohort Study

: Rotationplasty (RP) is a special surgical technique for bone tumors of the lower limb and is the chosen procedure for children under 6 with bone sarcoma in the distal femur. Leg reconstruction results in an unusual aspect of the limb potentially giving life-long emotional outcomes, especially considering the young age of most RP patients. Although the high level of the quality of life of these patients has been previously reported, aspects related to long-term psychological well-being, self-esteem and life satisfaction, particularly regarding the gender, procreation and parenting, have never been explored. The aim of this study was to assess the general degree of psychological well-being of RP patients, with specific reference to gender, procreation and parenting. Twenty long-term RP survivors of high-grade bone sarcoma participated in the study. They were administered the following validated questionnaires: HADS for psychological well-being (degree of anxiety and depression), Temperament and Character Inventory (TCI), RSES for self-esteem, SF-36 for quality of life, SWLS extended to life satisfaction, and ABIS for body image integration. Data on education, marriage, employment and parenthood were gathered. All the scores obtained were very close to normal references. The only gender difference was found for the TCI Cooperativeness scale, which was higher in women than in men. A satisfactory psychological well-being in terms of both self-esteem and integration of the prosthetic joint limb into one's body image, with relatively limited amount of anxiety/depression, good quality of life, and good temperament and character traits, was found. No major gender differences were reported

The Prognostic Value of Serum Biomarkers for Survival of Children with Osteosarcoma of the Extremities

Background: Osteosarcoma is a highly aggressive malignant bone tumor that affects mainly adolescents and young adults. We analyzed serum biomarkers for their prognostic significance in children with osteosarcoma. Methods: In this retrospective study, we investigated the prognostic factors in 210 children who were treated for appendicular osteosarcoma, including patient age and sex, tumor site and size (& GE;8 cm or <8 cm), presence of metastasis, chemotherapy-induced tumor necrosis, serum levels of alkaline phosphatase (AP), C-reactive protein, serum hemoglobin, lactate dehydrogenase, erythrocyte sedimentation rate (ESR), leukocyte counts, platelet count, and neutrophil-lymphocyte ratio. Results: A multivariate Cox regression model showed that high level of AP [HR of 1.73; 95% CI, 1.02 to 2.94], poor chemotherapy-induced tumor necrosis [HR of 2.40; 95% CI, 1.41 to 4.08] and presence of metastases at presentation [HR of 3.71; 95% CI, 2.19 to 6.29] were associated with poor prognosis at 5 years (p < 0.05). Inadequate surgical margins [HR 11.28; 95% CI, 1.37 to 92.79] and high levels of ESR [HR 3.58; 95% CI, 1.29 to 9.98] showed a greater risk of local recurrence at 5 years follow-up (p < 0.05). Conclusions: AP and ESR can identify osteosarcoma-diagnosed children with a greater risk of death and local recurrence, respectively

Techniques and machines for conservation and organic agriculture: the S.M.O.C.A. project.

The combination of low environmental impact farming techniques and conservation agriculture techniques is considered not feasible due to some limitations, mainly including is the strong dependence of conservation cropping systems by chemical control of weeds and the use of mineral fertilizers, which are considered essential for supporting to acceptable levels of crop productions. In order to apply the techniques of reduced tillage also in organic and integrated agriculture, is therefore indispensable, on one hand, the availability of specific versatile and efficient machines for non-chemical cover-crop management, weed control and sod-seeding/planting, on the other hand, the optimization of cropping systems in function of improved nutrient cycling and preventive weed control. The SMOCA project (Smart Management Conservation of Organic Agriculture) aims to integrate organic cropping systems and conservation agriculture techniques in three different scenarios (arable open field, open field vegetables and orchards) thanks to development of machines and technical itineraries that allow to apply the reduced tillage techniques even in the absence of pesticides. Within this project, prototypes of machines were realized in order to implement conservation cropping systems with high energy efficiency. For each scenario, three technical itineraries were compared: - control (INT): based on integrated agriculture without use of conservation agriculture techniques. The use of agrochemicals is allowed in accordance with the disciplinary for integrated production; - organic system (ORG): based on the organic agriculture, involves the use of cover crops (managed as green manure) and soil tillage. The non chemical management of weed flora is achieved with preventive methods and direct methods (mechanical and thermal weed control); - organic and conservation system (ORG +): based on the deep integration between the principles of conservation agriculture and organic farming. The system aims to achieve an almost continuous coverage of the soil through the use of no-tillage techniques and cover crops managed as living or dead mulches. The study of the overall sustainability of the different systems in comparison is conducted by means of a detailed analysis of the following aspects: - agronomic; - energy and environmental; - economic. The environmental effect of the compared systems will be mainly assessed through the study of the following aspects: greenhouse gas emissions, nutrient balance, preservation of soil quality, biological nitrogen fixation, conservation of water resources in the soil and the life cycle assessment (LCA). The efficiency and the impact of different management techniques are also continuously monitored on the orchard and vegetable crops through the study of the fruits of growth dynamics, thanks to an innovative methodology that uses a network of growth sensors spatially distributed in the field. The final product quality is also evaluated through the analysis of their levels of nutraceutical compounds. The research project is still ongoing and the prototypes of machines realized are presented in this paper