Osteosarcoma of the mobile spine†

Background The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine. Patients and methods Since 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome. Results The median age was 29 years (range 5-58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1-22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05). Conclusions Osteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcoma

Transgenic expression of human glial cell line-derived neurotrophic factor (hGDNF) from integration-deficient lentiviral vectors is neuroprotective in a rodent model of Parkinson's disease

Standard integration-proficient lentiviral vectors (IPLVs) are effective at much lower doses than other vector systems and have shown promise for gene therapy of Parkinson's disease (PD). Their main drawback is the risk of insertional mutagenesis. The novel biosafety-enhanced integration-deficient lentiviral vectors (IDLVs) may offer a significant enhancement in biosafety, but have not been previously tested in a model of a major disease. We have assessed biosafety and transduction efficiency of IDLVs in a rat model of PD, using IPLVs as a reference. Genomic insertion of lentivectors injected into the lesioned striatum was studied by linear amplification-mediated polymerase chain reaction (PCR), followed by deep sequencing and insertion site analysis, demonstrating lack of significant IDLV integration. Reporter gene expression studies showed efficient, long-lived, and transcriptionally targeted expression from IDLVs injected ahead of lesioning in the rat striatum, although at somewhat lower expression levels than from IPLVs. Transgenic human glial cell line-derived neurotrophic factor (hGDNF) expression from IDLVs was used for a long-term investigation of lentivector-mediated, transcriptionally targeted neuroprotection in this PD rat model. Vectors were injected before striatal lesioning, and the results showed improvements in nigral dopaminergic neuron survival and behavioral tests regardless of lentiviral integration proficiency, although they confirmed lower expression levels of hGDNF from IDLVs. These data demonstrate the effectiveness of IDLVs in a model of a major disease and indicate that these vectors could provide long-term PD treatment at low dose, combining efficacy and biosafety for targeted central nervous system applications

Influence of Cu(СH[3]COO)[2] promoting additive on bituminous coal oxidation process

The process of coal oxidation with applied Cu(СH[3]COO)[2] additive was studied by the capillary incipient wetness impregnation method with 5% mass concentration. The experiment was conducted by thermogravimetric analysis at a heating rate of 2.5°C/min to a maximum temperature of 600°C in atmospheric air. It was established that application of the initiation additive leads to a significant reduction in the initial temperature of sublimation and active oxidation of volatile compounds ([tau]Ti=78°C) and the oxidation end temperature ([tau]T[f]=64°C). It was established that in the presence of copper acetate the nature of coal oxidation reaction significantly changes (DTG data). The parameters of the coals oxidation process in the presence of copper acetate were determined, and an assumption was made about the presence of a composite catalytic effect

Whole-body magnetic resonance imaging in pediatric oncology — recommendations by the Oncology Task Force of the ESPR

The purpose of this recommendation of the Oncology Task Force of the European Society of Paediatric Radiology (ESPR) is to indicate reasonable applications of whole-body MRI in children with cancer and to address useful protocols to optimize workflow and diagnostic performance. Whole-body MRI as a radiation-free modality has been increasingly performed over the last two decades, and newer applications, as in screening of children with germ-line mutation cancer-related gene defects, are now widely accepted. We aim to provide a comprehensive outline of the diagnostic value for use in daily practice. Based on the results of our task force session in 2018 and the revision in 2019 during the ESPR meeting, we summarized our group’s experiences in whole-body MRI. The lack of large evidence by clinical studies is challenging when focusing on a balanced view regarding the impact of whole-body MRI in pediatric oncology. Therefore, the final version of this recommendation was supported by the members of Oncology Task Force

High-Grade Osteosarcoma of the Foot: Presentation, Treatment, Prognostic Factors, and Outcome of 23 Cooperative Osteosarcoma Study Group COSS Patients

Osteosarcoma of the foot is a very rare presentation of a rare tumor entity. In a retrospective analysis, we investigated tumor- and treatment-related variables and outcome of patients registered in the Cooperative Osteosarcoma Study Group (COSS) database between January 1980 and April 2016 who suffered from primary high-grade osteosarcoma of the foot. Among the 23 eligible patients, median age was 32 years (range: 6-58 years), 10 were female, and 13 were male. The tarsus was the most commonly affected site (n=16). Three patients had primary metastases. All patients were operated: 5 underwent primary surgery and 18 received surgery following preoperative chemotherapy. In 21 of the 23 patients, complete surgical remission was achieved. In 4 of 17 patients, a poor response to neoadjuvant chemotherapy was observed in the resected primary tumors. Median follow-up was 4.2 years (range: 0.4-18.5). At the last follow-up, 15 of the 23 patients were alive and 8 had died. Five-year overall and event-free survival estimates were 64% (standard error (SE) 12%) and 54% (SE 13%), which is similar to that observed for osteosarcoma in general. Event-free and overall survival correlated with primary metastatic status and completeness of surgery. Our findings show that high-grade osteosarcoma in the foot has a similar outcome as osteosarcoma of other sites

The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis

This article is available open access through the publisher’s website at the link below. Copyright @ 2013 The American Society of Gene & Cell Therapy.Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.Imperial College London, the Wellcome Trust, and Brunel University

Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR).

BACKGROUND Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. METHODS Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018) were retrospectively analyzed. RESULTS Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively. CONCLUSION Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups

HLA II class alleles in juvenile idiopathic arthritis patients with and without temporomandibular joint arthritis

Publisher Copyright: © 2016 Davidsone et al. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.Background: Temporomandibular joint (TMJ) arthritis is seen very often (38-87 %) in children with juvenile idiopathic arthritis (JIA). With contrast enhanced magnetic resonance imaging (MRI) we can detect more cases of TMJ arthritis than ever before. Previous studies show that HLA II class alleles may have protective or risk importance in JIA subtypes. Our objective is to identify HLA II class alleles of risk and protection in JIA patients with TMJ arthritis. Methods: During the period from 2010 to 2015 MRI for TMJ was performed in 85 JIA patients who were genotyped for HLA- DRB1; DQB1 and DQA1 using RT-PCR with sequence-specific primers. As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. Associations of DRB1; DQB1; DQA1 alleles in patients were examined individually using the χ 2 test. P-value (<0.05) and odds ratio were calculated using EPI INFO 6.0 software. Results: Out of 85 JIA patients with mean age of 13.7 ± 3.0 years (range 6.9-17.9 years), 59 (69 %) were girls and 26 (31 %) were boys. The mean duration of the disease was 3.07 ± 2.35 years (range 0.2-11.0 year). JIA subtypes were as follows: seronegative polyarthritis 51 (60 %), seropositive polyarthritis 6(7 %), oligoarthritis extended 7(8 %), oligoarthritis persistent 2 (2 %) arthritis with enthesitis 14 (17 %), undifferentiated 3 (4 %) and 2 (2 %) systemic arthritis. Two groups where separated after TMJ MRI exam: first with at least two signs of active inflammation and/or any structural damage (n = 62); second with no pathologic signs or with slight contrast enhancement (n = 23). We discovered that there are risk alleles that are found in all JIA patient's groups (MRI positive and negative groups) versus controls such as DRB1*07:01, DQB1*03:03; DQB1*05:01. Also some protective alleles as DRB1*18:01, DQB1*06:02-8 were found in overall JIA group. Alleles DRB1*12:01, DQB1*03:01; DQA1*05:01 were found to be protective for TMJ arthrits. Conclusion: In our study there were no convincing risk alleles, but there are alleles that probably are protective for TMJ arthritis like DRB1*12:01, DQB1*03:01; DQA1*05:01.publishersversionPeer reviewe

Teledermatology: Comparison of Store-and-Forward Versus Live Interactive Video Conferencing

A decreasing number of dermatologists and an increasing number of patients in Western countries have led to a relative lack of clinicians providing expert dermatologic care. This, in turn, has prolonged wait times for patients to be examined, putting them at risk. Store-and-forward teledermatology improves patient access to dermatologists through asynchronous consultations, reducing wait times to obtain a consultation. However, live video conferencing as a synchronous service is also frequently used by practitioners because it allows immediate interaction between patient and physician. This raises the question of which of the two approaches is superior in terms of quality of care and convenience. There are pros and cons for each in terms of technical requirements and features. This viewpoint compares the two techniques based on a literature review and a clinical perspective to help dermatologists assess the value of teledermatology and determine which techniques would be valuable in their practice