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The ability of SiC devices to switch at high speed allows increasing significantly the power density in both converters and passive components, reducing their required size. To mitigate harmonic injection form inverters into the grid, in order to comply with power quality standards, an accurate filter design is required. Given its excellent performance, an LCL filter is the configuration most suitable in grid-connected power converters. Several parameters must be considered when designing an effective LCL filter, and the inverter-side inductor assumes a special importance because of its relevance to suppress high frequency harmonic content at the inverter side. One of the most relevant issues to be considered in the process of designing the LCL filter is the evaluation of core losses in the inverter-side inductor, which will determine the final temperature of the inductor. This paper analyses the core losses of the inverter-side inductor of an LCL filter. The proposed method is based on the computation of the current harmonics generated by the inverter and on Steinmetz’s empirical equation. As a result, core losses calculated taking into account several carrier and sideband harmonics show good agreement with the experimental values. When current harmonics are estimated by simulation, as it is done in the proposed design procedure, results are less accurate, but precise enough for a design procedure.

The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBXI) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBXI showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBXI had a significantly higher cumulative incidence of relapse, especially among patients aged >= 35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of >3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with >3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corre-sponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying kar-yotypes with >3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), inde-pendently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Addi-tional molecular analyses of patients carrying >3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel tar-geted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9–8.6) months, with a 4-year OS probability of 18% (95% CI, 9%–27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109–3.362), 2.958 (1.640–5.334), and 2.976 (1.157–7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL., La Caixa" Foundation and ISCIII, Grant/ Award Number: PI19/01828; Generalitat de Catalunya (GRC), Grant/Award Number: 2017 SGR288

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high-risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome-negative B-cell progenitor ALL patients treated according to the Programa Espanol de Tratamientos en Hematologia protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD-negative after induction therapy.

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day).

In the present paper we have used a three-color immunofluorescence procedure combined with flow cytometry cell analysis and sorting for the identification and enumeration of human mast cells in both normal and pathological bone marrow samples. Our results show that bone marrow mast cells are clearly identifiable on the basis of their light-scatter properties and strong CD117 expression. These cells were negative for the CD34, CD38, and BB4 antigens. In addition, they were CD33+ and displayed a high reactivity for the anti-IgE monoclonal antibody. The identity of the CD117-strong+ cells (mast cells) was confirmed by both microscopic examination and flow cytometry analysis. The overall frequency of mast cells in the bone marrow samples analyzed in the present study was constantly lower than 1%. The lowest frequencies corresponded to normal human bone marrow samples (0.0080 +/- 0.0082%) and the highest to those patients suffering from indolent systemic mast cell disease (0.40 +/- 0.13%). In summary, our results show that the identification and enumeration of bone marrow mast cells can be achieved using multiparametric flow cytometry. Moreover, once identified, mast cells are suitable for being characterized from the phenotypic and the functional point of view, facilitating the comparison between normal and abnormal mast cells.

Out of a group of 220 acute lymphoblastic leukaemias (ALL) with phenotypic study at diagnosis, 18 were selected on which sequential studies were performed due to relapse (15 cases) or to lack of achievement of complete remission (primary resistant ALL, 3 cases). The purpose of this study was to analyse the incidence and characteristics of the possible antigenic changes with regard to the diagnosis. Along with the classic markers, a panel comprised of 20 monoclonal antibodies against lymphoid and myeloid antigens was used. Major phenotypic changes (acquisition of myeloid antigens CD13 and CD33) were found only in one case amongst the relapsing ALL (7%). Seven other patients (47%) showed minor phenotyping changes, including: 1) acquisition or loss of antigens (2 cases); 2) changes in more then 50% of any antigen's expression (4 cases); 3) both (1 case). These results might suggest that antigenic changes are rather frequent in relapsing ALL; however, none of such changes modified in our experience the phenotypic diagnosis so any change of this last should be regarded as an exceptional event. The majority of these antigenic changes consisted of the loss of maturation antigens (CD20) or acquisition of early markers (TdT, HLA-DR) or activation markers (CD38); this would mean that the relapsing blast cells show a functional status of activation and proliferation, with a phenotype more immature than that of the diagnosis, thus explaining the poorer prognosis of the patients in relapse. No phenotypic changes were found in the primary resistant ALL, which may indicate the persistence of the original cell clone without any alteration.

INTRODUCTION Multiple cranial neuropathy or polineuritis cranealis is rarely seen in everyday clinical practice. It is considered to be a topographically circumscribed form of the Guillain-Barre syndrome. The cases described have a wide range of clinical and biological characteristics. Some of these may be due to infectious agents. CLINICAL CASE We present the case of a 50 year old man with acute onset of diplopia, dysphagia, anarthria, cervical and right arm flexor-extensor muscle weakness due to involvement of many motor cranial nerves and superior cervical nerve roots. On neurological examination there was mixed involvement, mainly of the axons of the nerve trunks involved. Studies to determine aetiology did not show any demonstrable agent. DISCUSSION AND CONCLUSIONS Different topographical varieties of the Guillain-Barre syndrome have been described, including: Fisher's syndrome, pharyngo-cervico-brachial paralysis, arreflexive paraparesia, bilateral facial paralysis with paraesthesias, hyporeflexia and bilateral lumbar polyradiculopathy. We compare the clinical characteristics of our patient with those described in the literature. We found a degree of heterogenicity in the clinical and biological characteristics of the cases described, which may mean that they had different aetiologies. Therefore, we consider that before labelling these conditions as atypical variants of the Guillain-Barre syndrome, a thorough search should be made for a precise aetiology.

INTRODUCTION The mesencephalic alternating syndromes or syndromes of Weber, Benedikt and Claude are uncommon in clinical practice. They are caused by a lesion in the mesencephalus which affects the third cranial nerve bundle, together with the corticospinal pathway, subthalamic nucleus and the dentato-rubric path. CLINICAL CASE We present the case of a normotensive patient who, as a consequence of a hematoma in the mesencephalic tegmentum, had the association of these three syndromes consecutively. The clinical course was favorable, so that after three months of follow-up only paralysis of the third cranial nerve bundle persisted. DISCUSSION In the syndromes of Weber, Benedikt and Claude there is the association of ophthalmoplegia with hemiplegia, or a cerebellar hemisyndrome or contralateral abnormal movements compatible with hemiballismus, respectively. Amongst the commonest causes are expansive processes, tumors and arteriovenous malformations. More rarely they are due to cerebrovascular accidents, which are usually ischemic and occasionally hemorrhagic in aetiology. CONCLUSIONS Spontaneous mesencephalic hematomas are infrequent. They make up approximately 1% of all intracranial hematomas. The commonest site is the tegmentum followed by the peduncle and tectum. They have better prognosis than other hematomas of the brainstem.