Increased phospho-mTOR expression in megakaryocytic cells derived from CD34+ progenitors of essential thrombocythaemia and myelofibrosis patients

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Quality control of B-lines analysis in stress Echo 2020

Background The effectiveness trial “Stress echo (SE) 2020” evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. Purpose To provide web-based upstream quality control and harmonization of B-lines reading criteria. Methods 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. Results All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). Conclusions Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.info:eu-repo/semantics/publishedVersio

La nostra esperienza nel trattamento chirurgico dei tumori mesenchimali dello stomaco

Gli Autori hanno eseguito lo studio retrospettivo di una serie di 22 malati operati per tumore mesenchimale gastrico nel periodo dal 1974 al 2003 al fine di rivedere i casi alla luce delle più moderne acquisizioni istopatologiche ed immunoistochimiche e di analizzare il valore diagnostico delle manifestazioni cliniche, delle indagini strumentali impiegate e dei principi che hanno regolato la tattica chirurgica. Gli Autori concludono sottolineando come non esistano segni e sintomi specifici della patologia che consentano un orientamento diagnostico. L’esame endoscopico svolge un ruolo diagnostico importante, mentre la TC è l’esame più attendibile per la definizione della sede, dei rapporti e della diffusione della neoplasia. L’obiettivo del trattamento deve essere la completa asportazione del tumore con un margine di clearance di 2-3 cm

<i>Leishmania</i> Infection during Ruxolitinib Treatment: The Cytokines-Based Immune Response in the Setting of Immunocompromised Patients

Ruxolitinib is a JAK1/2 inhibitor that has revolutionized the approach to myelofibrosis. On the one side, this drug can rapidly improve the symptoms related to the hematological disease; on the other side, the inhibition of JAK1/2 can lead to immunosuppression which may increase the risk of infections, due to a change in the cytokine balance in favor of anti-inflammatory cytokines, to direct inhibition of immune cells, and to the suppression in the production of specific antibodies. In this patient setting, much is known about possible viral and bacterial infections, while little is reported in the literature concerning parasitic infections, specifically leishmaniasis. Leishmania is a parasitic infection that can cause serious problems in immunosuppressed patients. The parasite can invade the bloodstream and cause a wide range of symptoms, including fever, weight loss, and anemia. In severe cases, it can lead to multi-organ failure and, rapidly, death. Early diagnosis and prompt treatment are essential especially for these patients, unable to respond adequately. In this case and the following review of the existing literature, the cytokine kinetics and the production of specific anti-Leishmania antibodies represent characteristic aspects capable of providing a more in-depth understanding of the mechanisms underlying these complex clinical cases in an immunocompromised patient

A case of high‐risk AML in a patient with advanced systemic mastocytosis

Abstract Aggressive SM + AML has limited therapeutic options. Even a strong combination of decitabine–venetoclax–midostaurin has a transient effect on AML and a mitigated effect on SM. Larger series are required to identify the best therapeutic strategy

Comparison of JAK2V617F-positive essential thrombocythaemia and early primary myelofibrosis: The impact of mutation burden and histology

An accurate histological diagnosis may distinguish essential thrombocythaemia (ET) from early primary myelofibrosis (early-PMF), which is associated with worse outcome. Outcome of ET is also negatively affected by the presence of the JAK2V617F mutation. To investigate the impact of JAK2V617F mutation burden and histology on outcome, we collected 475 WHO-diagnosed ET (69.2%) or early-PMF JAK2V617F -positive patients followed in 4 Italian haematology centers. JAK2V617F allele burden was ≤50% in 90% and 87% of ET and early-PMF patients, respectively (P = .34). During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28 (5.8%) patients had died. In early-PMF compared to ET, the 10-year mortality rates (6.7% and 4.3%, P = .73), leukemic transformation rates (1.4% and 1.2%, P = .45), and thrombosis rates (16.7% and 12.2%, P = .12) were comparable. Only progression to overt myelofibrosis at 10 years was significantly worse (11.4% and 1.5%, P = .004). In multivariate analysis, a higher (&gt;50%) JAK2V617F burden was significantly correlated with fibrotic progression and histology. Considering JAK2V617F -positive disease, a higher (&gt;50%) JAK2V617F burden and histological classification are independent prognostic risk factors for disease progression. These findings reinforce the need for standardized detection of this mutation

Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

1. We investigated the effects of prolonged exposure to copper (Cu(2+)) on vascular functioning of isolated rat aorta. 2. Aortic rings were exposed to CuSO(4) (3–24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu(2+). 3. Exposure to 2 μM Cu(2+) in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 μM PE by 30% (P<0.05) and impaired the relaxant response to 3 μM ACh or 1 μM A23187 (ACh, from 65.7±7.1 to 6.2±1.1%, n=8; A23187, from 74.6±8.2 to 12.0±0.8%, n=6; P<0.01 for both). Cu(2+) exposure did not affect the relaxant response to NO-donors. 4. Impairment of vasorelaxation appeared 3 h after incubation with 2 μM Cu(2+) and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2±6.4%, n=10, P<0.01 vs Cu(2+) alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. 5. Twenty-four hour-exposure to 2 μM Cu(2+) did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8±1.1 to 18.9±2.9 ng mg(−1) wet weight, n=8; P<0.01. 6. Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu(2+) impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions