Donor-transmitted Triple-Hit Lymphoma in a Renal Allograft Recipient

simultaneous appearance of DLBCL in the donor and recipient after renal transplantatio

Digital droplet PCR is a specific and sensitive tool for detecting IDH2 mutations in acute myeloid leukemia patients

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) interfere with cellular metabolism contributing to oncogenesis. Mutations of IDH2 at R140 and R172 residues are observed in 20% of acute myeloid leukemias (AML), and the availability of the IDH2 inhibitor Enasidenib made IDH2 mutational screening a clinical need. The aim of this study was to set a new quantitative polymerase chain reaction (PCR) technique, the drop-off digital droplet PCR (drop-off ddPCR), as a sensitive and accurate tool for detecting IDH2 mutations. With this technique we tested 60 AML patients. Sanger sequencing identified 8/60 (13.5%) mutated cases, while ddPCR and the amplification refractory mutation system (ARMS) PCR, used as a reference technique, identified mutations in 13/60 (21.6%) cases. When the outcome of IDH2-mutated was compared to that of wild-type patients, no significant difference in terms of quality of response, overall survival, or progression-free survival was observed. Finally, we monitored IDH2 mutations during follow-up in nine cases, finding that IDH2 can be considered a valid marker of minimal residual disease (MRD) in 2/3 of our patients. In conclusion, a rapid screening of IDH2 mutations is now a clinical need well satisfied by ddPCR, but the role of IDH2 as a marker for MRD still remains a matter of debate

Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation

Background: The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient’s inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation. Methods: Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume. Results: Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods. Conclusions: Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions

The assessment of minimal residual disease versus that of somatic mutations for predicting the outcome of acute myeloid leukemia patients

Background: In addition to morphological and cytogenetic features, acute myeloid leukemias are characterized by mutations that can be used for target-therapy; also the minimal/measurable residual disease (MRD) could be an important prognostic factor. The purpose of this retrospective study was to investigate if somatic mutations could represent an additional prognostic value in respect of MRD alone. Method: At baseline, 98 patients were tested for NPM1, FLT3, and for WT1 expression; 31 for ASXL1, TET2, IDH1, IDH2, N-RAS, WT1, c-KIT, RUNX1, and DNMT3A. The same genes have been also tested after induction and consolidation. Results: Overall, 60.2% of our patients resulted mutated: 24.5% carried mutations of FLT3-ITD, 38.7% of NPM1, 48.4% of c-KIT, 25.8% of N-RAS and 19.3% of IDH2. The probability of achieving a complete response (CR) was higher for younger patients, with low ELN risk score, NPM1-mutated, with low WT1 levels, and without FLT3. The presence of additional mutations represented a poor predictive factor: only 19% of these cases achieved CR in comparison to 43% of subjects without any of it. Concerning survival, it was conditioned by a lower ELN risk score, younger age, reduction &gt; 1 log of the NPM1 mutational burden, disappearance of FLT3 mutations and lower WT1 expression. Regarding the role of the additional mutations, they impaired the outcome of 20% of the already MRD-negative patients. Concerning the possibility of predicting relapse, we observed an increase of the NPM1 mutational burden at the time-point immediately preceding the relapse (about 2 months earlier) in 50% of subjects. Similarly concerning WT1, an increase of its expression anticipated disease recurrence in 64% of cases. Conclusions: We demonstrated that additional somatic mutations are able to impair outcome of the already MRD-negative subjects. About MRD, we suggest a prognostic role also for the WT1 expression. Finally, we considered as relevant the assessment of NPM1 quantity clearance instead of the presence/absence of mutations alone. Still remains in doubt the utility in terms of long-term prognosis of a baseline more complex mutational screening; we could hypothesize that it would be useful for those patients where other markers are not available or who reached the MRD negativity

Subjective well-being nel disturbo bipolare : uno studio prospettico preliminare

Aims: Recently numerous studies have focused their attention on the importance of patients' self evaluation of the impact of pharmacotherapy on quality of life. These aspects have led to the introduction of new assessments in psychiatric care in order to help clinicians in evaluating patients' perspective and subjective well-being. To date, several studies have investigated subjective well-being among schizophrenic patients, whereas there are few such studies in bipolar patients. This study aims at evaluating the association between subjective well-being and psychopathology in bipolar patients subjected to drug treatment with atypical antipsychotics and mood stabilizers at the time of admission to the psychiatric ward and during a follow-up period. Methods: A consecutive sample of thirty in-patients with a diagnosis of bipolar disorder (DSM IV-TR) was recruited in the psychiatric ward of the Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milan. They were studied on admission (TO), at discharge (T1) and then at 6 (T2), 12 (T3) and 18 weeks (T4) after discharge (Fig. 1). Psychopathology was rated with the Brief Psychiatric Rating Scale (BPRS), while subjective well-being was assessed with the Subjective Well-being under Neuroleptic treatment scale (SWN). Associations between BPRS and SWN scores were analyzed using Pearson's correlation coefficients. In addition, a linear regression analysis was conducted using SWN at the end of follow-up (T4) as the dependent variable and demographic and clinical characteristics as possible predictors. Results: Non-linear relations best described the associations between changes in BPRS and SWN scores over time: no association was found during the acute phase (from admission to T1), while cross-sectional Pearson's correlation coefficients indicate inverse associations between SWN and BPRS scores at T2 (r = -0.598, p = 0.014) and between SWN at T2 and BPRS score at T4 (r = -0.84 7, p = 0.009) (Table I). Moreover, linear regression showed that variance in SWN at T4 was mostly accounted for by the effect of number of admissions (standardized B -0.551, p = 0.021) and SWN score at T2 (standardized B 1.262; p = 0.001) (Table II). Conclusions: Our results point-out that modifications in subjective well-being and psychopathological state were not linearly related in bipolar patients, thus suggesting that subjective well-being could be considered in these patients as a personal variable associated to psychopathological state in a different way according to phase of illness. Further research including wider samples and longer follow-up periods are needed in to confirm our results and identify other possible correlations

Towards a more energy efficient stormwater management in smart Mediterranean cities

Escuder Bueno, I.; Andrés Doménech, I.; Perales Monparler, S.; Morales Torres, A.; Rossetto, R.; Bonari, E.; Ciabatti, S.... (2014). Verso una gestione più efficiente delle acque meteoriche nelle città del Mediterraneo. Acque Sotterranee. 3(2):59-60. doi:10.7343/AS-075-14-0101S59603

PO-0773: Reirradiation by extracranial stereotactic treatment: preliminary results of a dose escalation study

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The hOCT1 and ABCB1 polymorphisms do not influence the pharmacodynamics of nilotinib in chronic myeloid leukemia

First-line nilotinib in chronic myeloid leukemia is more effective than imatinib to achieve early and deep molecular responses, despite poor tolerability or failure observed in one-third of patients. The toxicity and efficacy of tyrosine kinase inhibitors might depend on the activity of transmembrane transporters. However, the impact of transporters genes polymorphisms in nilotinib setting is still debated. We investigated the possible correlation between single nucleotide polymorphisms of hOCT1 (rs683369 [c.480C > G]) and ABCB1 (rs1128503 [c.1236C > T], rs2032582 [c.2677G > T/A], rs1045642 [c.3435C > T]) and nilotinib efficacy and toxicity in a cohort of 78 patients affected by chronic myeloid leukemia in the context of current clinical practice. The early molecular response was achieved by 81% of patients while 64% of them attained deep molecular response (median time, 26 months). The 36-month event-free survival was 86%, whereas 58% of patients experienced toxicities. Interestingly, hOCT1 and ABCB1 polymorphisms alone or in combination did not influence event-free survival or the adverse events rate. Therefore, in contrast to data obtained in patients treated with imatinib, hOCT1 and ABCB1 polymorphisms do not impact on nilotinib efficacy or toxicity. This could be relevant in the choice of the first-line therapy: patients with polymorphisms that negatively condition imatinib efficacy might thus receive nilotinib as first-line therapy