61 research outputs found

    Standardization of BCR-ABL1 p210 Monitoring: From Nested to Digital PCR

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    The introduction of tyrosine kinase inhibitors in 2001 as a targeted anticancer therapy has significantly improved the quality of life and survival of patients with chronic myeloid leukemia. At the same time, with the introduction of tyrosine kinase inhibitors, the need for precise monitoring of the molecular response to therapy has emerged. Starting with a qualitative polymerase chain reaction, followed by the introduction of a quantitative polymerase chain reaction to determine the exact quantity of the transcript of interest-p210 BCR-ABL1, molecular monitoring in patients with chronic myeloid leukemia was internationally standardized. This enabled precise monitoring of the therapeutic response, unification of therapeutic protocols, and comparison of results between different laboratories. This review aims to summarize the steps in the diagnosis and molecular monitoring of p210 BCR-ABL1, as well as to consider the possible future application of a more sophisticated method such as digital polymerase chain reaction

    ADDICTIONS SUBSTANCE FREE DURING LIFESPAN

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    The addictions substance free is an umbrella definition comprises internet addiction, sexual addiction, gambling pathological, workholism, videogames and computer addiction. Actually, the technological addictions is frequent in young adolescents. The term Digital Natives indicates the children born in an information system of learning and communication different from that of the generations previous. This temporal range was strongly characterized by growing presence of technological communication toolsin daily life. The effects of hyper-exposition to technological tools tend to create a relational virtuality without a body is born,therefore, already within the family ties and during adolescence he moved to the digital socialization network. The technological object it interacts between the adolescent and the world of peers and adults, becoming the facilitator object that as the psychotropic substance, it conveys new modes of communicatio

    The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRα-positive hypereosinophilic syndrome. Results of a multicenter prospective study

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    BACKGROUND AND OBJECTIVES: The hypereosinophilic syndrome (HES) may be associated with the fusion of the platelet derived growth factor receptor a (PDGFRalpha) gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated PDGFRalpha tyrosine kinase. These cases with FIP1L1-PDGFRalpha rearrangement have been reported to be very sensitive to the tyrosine kinase inhibitor imatinib mesylate. DESIGN AND METHODS: A prospective multicenter study of idiopathic or primary HES was established in 2001 (Study Protocol Registration no. NCT 0027 6929). One hundred and ninety-six patients were screened, of whom 72 where identified as having idiopathic or primary HES and 63 were treated with imatinib 100 to 400 mg daily. RESULTS: Twenty-seven male patients carried the FIP1L1-PDGFRalpha rearrangement. All 27 achieved a complete hematologic remission (CHR) and became negative for the fusion transcripts according to reverse transcriptase polymerase chain reaction (RT-PCR) analysis. With a median follow-up of 25 months (15-60 months) all 27 patients remain in CHR and RT-PCR negative, and continue treatment at a dose of 100 to 400 mg daily. In three patients imatinib treatment was discontinued for few months, the fusion transcript became rapidly detectable, and then again undetectable upon treatment reassumption. Thirty-six patients did not carry the rearrangement; of these, five (14%) achieved a CHR, which was lost in all cases after 1 to 15 months. INTERPRETATION AND CONCLUSIONS: All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFRalpha rearrangement. For all patients with this rearrangement, chronic imatinib treatment at doses as low as 100 mg daily ensures complete and durable responses

    Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

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    Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

    MULTICOMPONENT BIOMIMETIC SYSTEMS FOR BONE AND OSTEOCHONDRAL DEFECTS

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    The extracellular matrix of bone has been described as a composite material made constituted by collagen type I fibrils mineralized with nanocrystals of hydroxyapatite. Approximately 70% of bone by weight is composed of calcium salts, with hydroxyapatite Ca10(PO4)6(OH)2 as the primary mineral constituent. Bone formation occurs in two phases: matrix synthesis followed by extracellular mineralization. An impaired balance of bone resorption and formation by osteoclasts and osteoblasts, respectively, induces osteoporosis. Other bone defects can be caused by tumor removal, fractures (especially in the hip, wrist, knee and spine) or congenital defects. A more complex substrate is represented by osteochondral tissue, where defects penetrate the subchondral bone. To mimic natural structure, we propose different approaches to repair bone and osteochondral defects and to promote a potential bone healing filler. In general, injectable materials (cements/natural polymer) hold great promise in tissue engineering applications due to the ability of these systems to conform to complex bone shapes, contours, and defects with less invasive surgery. The target is the osteogenic differentiation induced by bioactive component (natural polymers and/or modified hydroxyapatite) of the injectable systems. In this work, we proposed the following bone filler materials: 1. Strontium-substituted hydroxyapatite cement (to contrast bone resorpsion). 2. Bioactive hydroxyapatite - graphene oxide (to support high viability and osteogenic differentiation of hMSC cells). 3. Modified-cellulose hydrogels crosslinked by citric acid (to increase hydrophilicity and roughness surface in order to stimulate osteogenic differentiation of hMSC). Osteocondral region has two distinct tissues (bone and cartilage) with different properties: to mimic its structure, we realized two different gelatin scaffolds biomineralized by HA. The use of a 3D scaffold depends on the necessity to provide a shape control, while the biological signals are induced by HA presence, realized by bulk sol-gel transition, and surface biomimetic treatment, as reported in the two type of scaffolds realized: 1. Gelatin scaffold crosslinked by EDC solution, and biomineralized by modified Kokubo treatment (to increase osteogenic proliferation and differentiation); 2. Gelatin/hydroxyapatite scaffold realized by in situ sol-gel synthesis and crosslinked by EDC solution (where the biological signals occur into the scaffold as a gradient and crystalline degree is modulated by gelatin/hydroxyapatite ratio)
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