A Case of Atypical Delayed and Prolonged Hematologic Toxicity With Azacitidine in Chronic Myelomonocytic Leukemia (CMML) and Review of Literature

Hypomethylating drugs are useful and have been approved for the treatment of myelodysplastic syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS, have included only a small number of patients with CMML, and there are just a few specific reports on CMML patients. The Azacitidine is actually authorised for the treatment of CMML patients with 10–29% marrow blasts without myeloproliferative disorder, who are not eligible for haematopoietic stem cell transplantation. This hypomethylating agent in MDS is known for causing transient cytopenias, most often occurring during the first 2 cycles. Here we report a case of an atypical delayed and prolonged hematologic toxicity during Azacitidine treatment in a CMML patient; furthermore we also reviewed the literature regarding the efficacy of the drug and the management of hematologic adverse effects, in term of dose adjustments or alternative schedule of administration, in specific CMML setting

Successful treatment with T depleted autologous peripheral blood stem cell transplantation of refractory chronic autoimmune thrombocytopenic purpura

Autoimmune thrombocytopenia (AITP) is a disorder due to specific platelet auto-antibodies directed against platelet surface glycoproteins. AITP in adults is usually chronic, idiopathic and frequently refractory to conventional treatments. Myelo- and immuno- suppressive chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation is an experimental approach for severe chronic refractory AITP. We report a case of a woman with AITP, refractory to the conventional therapy, submitted to T-cell-depleted autologous PBSC transplantation, which obtained long term stable response on platelet count. We deem that the positive outcome of our patient depends on T-cells depletion of the graft, which reduces autoreactive T clones

Piani di cottura (parte di -)

Il progetto M-Stekio si è basato sullo sfruttamento dei brevetti d’invenzione di 3P Engineering. Tali brevetti consentono di ottenere un bruciatore a gas caratterizzato da: ingombri ridotti, maggior efficienza energetica, aumento della sicurezza, riduzione del consumo di gas, dei tempi di cottura e delle emissioni nocive. Poiché la novità tecnologica del prodotto è ciò che maggiormente lo caratterizza, i designer che hanno lavorato al progetto sono docenti del Politecnico, con ottime competenze dal punto di vista della tecnologia (di prodotto e di processo) e dell’ingegnerizzazione. Questo ha consentito al gruppo di ricerca di lavorare fianco a fianco con gli ingegneri di 3P Engineering, mantenendo ognuno le proprie specifiche competenze

Quality performance measures for small capsule endoscopy: Are the ESGE quality standards met?

Background and study aims The European Society of Gastrointestinal Endoscopy (ESGE) recently issued a quality performance measures document for small bowel capsule endoscopy (SBCE). The aim of this nationwide survey was to explore SBCE practice with ESGE quality measures as a benchmark. Patients and methods A dedicated per-center semiquantitative questionnaire based on ESGE performance measures for SBCE was created by a group of SBCE experts. One-hundred-eighty-one centers were invited to participate and were asked to calculate performance measures for SBCE performed in 2018. Data were compared with 10 ESGE quality standards for both key and minor performance measures. Results Ninety-one centers (50.3 %) participated in the data collection. Overall in the last 5 years (2014–2018), 26,615 SBCEs were performed, 5917 of which were done in 2018. Eighty percent or more of the participating centers reached the minimum standard established by the ESGE Small Bowel Working Group (ESBWG) for four performance measures (indications for SBCE, complete small bowel evaluation, diagnostic yield and retention rate). Conversely, compliance with six minimum standards established by ESBWG concerning adequate bowel preparation, patient selection, timing of SBCE in overt bleeding, appropriate reporting, reading protocols and referral to device-assisted enteroscopy was met by only 15.5%, 10.9%, 31.1%, 67.7%, 53.4%, and 32.2% of centers, respectively. Conclusions The present survey shows significant variability across SBCE centers; only four (4/10: 40 %) SBCE procedural minimum standards were met by a relevant proportion of the centers ( ≥ 80 %). Our data should help in identifying target areas for quality improvement programs in SBCE

Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment

Migration, Mobility and Human Rights at the Eastern Border of the European Union - Space of Freedom and Security

This edited collection of migration papers would like to emphasise the acute need for migration related study and research in Romania. At this time, migration and mobility are studied as minor subjects in Economics, Sociology, Political Sciences and European Studies only (mostly at post-graduate level). We consider that Romanian universities need more ‘migration studies’, while research should cover migration as a whole, migration and mobility being analysed from different points of view – social, economical, legal etc. Romania is part of the European Migration Space not only as a source of labourers for the European labour market, but also as source of quality research for the European scientific arena. Even a country located at the eastern border of the European Union, we consider Romania as part of the European area of freedom, security and justice, and therefore interested in solving correctly all challenges incurred by the complex phenomena of migration and workers’ mobility at the European level. The waves of illegal immigrants arriving continuously on the Spanish, Italian and Maltese shores, and the workers’ flows from the new Member States from Central and Eastern Europe following the 2004 accession, forced the EU officials and the whole Europe to open the debate on the economical and mostly social consequences of labour mobility. This study volume is our contribution to this important scientific debate. Starting with the spring of 2005, the Jean Monnet European Centre of Excellence and the School of High Comparative European Studies (SISEC), both within the West University of Timisoara, have proposed a series of events in order to raise the awareness of the Romanian scientific environment on this very sensitive issues: migration and mobility in the widen European Space. An annual international event to celebrate 9 May - The Europe Day was already a tradition for SISEC (an academic formula launched back in 1995 in order to prepare national experts in European affairs, offering academic post-graduate degrees in High European Studies). With the financial support from the Jean Monnet Programme (DG Education and Culture, European Commission), a first migration panel was organised in the framework of the international colloquium ‘Romania and the European Union in 2007’ held in Timisoara between 6 and 7 of May 2005 (panel Migration, Asylum and Human Rights at the Eastern Border of the European Union). Having in mind the positive welcoming of the migration related subjects during the 2005 colloquium, a second event was organised on 5 May 2006 in the framework of the European Year of Workers’ Mobility: the international colloquium Migration and Mobility: Assets and Challenges for the Enlargement of the European Union. In the same period, the Jean Monnet European Centre of Excellence, SISEC and The British Council in Bucharest have jointly edited two special issues of The Romanian Journal of European Studies, no.4/2005 and 5-6/2006, both dedicated to migration and mobility. Preliminary versions of many of the chapters of this volume were presented at the above mentioned international events. The papers were chosen according to their scientific quality, after an anonymously peer-review selection. The authors debate both theoretical issues and practical results of their research. They are renowned experts at international level, members of the academia, PhD students or experienced practitioners involved in the management of the migration flows at the governmental level. This volume was financed by the Jean Monnet Programme of the Directorate General Education and Culture, European Commission, throughout the Jean Monnet European Centre of Excellence (C03/0110) within the West University of Timisoara, Romania, and is dedicated to the European Year of Workers’ Mobility 2006. Timisoara, December 200

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings

Integrated Genomic, Functional, and Prognostic Characterization of Atypical Chronic Myeloid Leukemia

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1-negative clonal disorder, which belongs to the myelodysplastic/myeloproliferative group. This disease is characterized by recurrent somatic mutations in SETBP1, ASXL1 and ETNK1 genes, as well as high genetic heterogeneity, thus posing a great therapeutic challenge. To provide a comprehensive genomic characterization of aCML we applied a high-throughput sequencing strategy to 43 aCML samples, including both whole-exome and RNA-sequencing data. Our dataset identifies ASXL1, SETBP1, and ETNK1 as the most frequently mutated genes with a total of 43.2%, 29.7 and 16.2%, respectively. We characterized the clonal architecture of 7 aCML patients by means of colony assays and targeted resequencing. The results indicate that ETNK1 variants occur early in the clonal evolution history of aCML, while SETBP1 mutations often represent a late event. The presence of actionable mutations conferred both ex vivo and in vivo sensitivity to specific inhibitors with evidence of strong in vitro synergism in case of multiple targeting. In one patient, a clinical response was obtained. Stratification based on RNA-sequencing identified two different populations in terms of overall survival, and differential gene expression analysis identified 38 significantly overexpressed genes in the worse outcome group. Three genes correctly classified patients for overall survival