124 research outputs found
Erratum: Envisioning translational hyperscanning: how applied neuroscience might improve family-centered care (Social Cognitive and Affective Neuroscience (2022) (nsac061) DOI: 10.1093/scan/nsac061)
No full textThis is a correction to: Elisa Roberti, Elena Capelli, Livio Provenzi Envisioning translational hyperscanning: how applied neuroscience might improve family-centered care, Social Cognitive and Affective Neuroscience, 2022; nsac061, https://doi.org/10.1093/scan/nsac061 In the originally published version of this manuscript, the order of authors and the authors’ affiliations were incorrectly given as follows: Livio Provenzi,1,2 Elisa Roberti,2 and Elena Capelli2 1Department of Brain and Behavioral Sciences, University of Pavia, Pavia 27100, Italy 2Developmental Psychobiology Lab, IRCCS Mondino Foundation, Pavia 27100, Italy The Publisher apologizes for this error, which occurred during the production process. The author list and authors’ affiliations have now been corrected, as follows: Elisa Roberti,1 Elena Capelli,1 and Livio Provenzi2,1 1Developmental Psychobiology Lab, IRCCS Mondino Foundation, Pavia 27100, Italy 2Department of Brain and Behavioral Sciences, University of Pavia, Pavia 27100, Ital
Secondary Acute Myeloid Leukemia: Pathogenesis and Treatment
No full textSecondary acute myeloid leukemia includes acute myeloid leukemia that arises either from a previous myeloid hematologic disease such as myelodysplastic syndrome, chronic myeloproliferative syndrome, or myelodysplastic/myeloproliferative overlap syndromes or from a previous chemotherapy or radiotherapy performed for another disease. Secondary acute myeloid leukemia is characterized by a worse prognosis than its de novo counterparts, with a 5-year overall survival of <30% despite an advanced insight into pathogenesis and new available treatments. The best therapeutic strategy is to achieve complete remission with a negative minimal residual disease followed by hematopoietic stem cell transplantation; however, advanced age of patients at diagnosis, multiple comorbidities, and lower rate of complete remission makes these approaches available only for a small fraction of secondary acute myeloid leukemia patients. In this chapter, we discuss the epidemiology, pathogenesis, and prognostic factors of secondary acute myeloid leukemia. Also, we discuss the main treatments currently available for eligible patients (fit patients) and non-eligible patients (unfit patients) for intensive chemotherapy and future treatment perspectives.
Copyright: The Authors.; The authors confirm that the materials included in this chapter do not violate copyright laws. Where relevant, appropriate permissions have been obtained from the original copyright holder(s), and all original sources have been appropriately acknowledged or referenced
Il processo di Parigi del 1240 contro il Talmud: verso un’edizione critica del testo ebraico
No full textThe article summarizes the main events of the trial held at Paris in 1240 under Louis IX against the Babylonian Talmud; the trial resulted in the first burning of the Talmud in European history (1242 or 1244). The author deals with the textual history of the Hebrew statement of the trial, which has still not received a proper critical edition. Four extant manuscripts of this work are held in the National Libraries at Paris, Hamburg and Moscow and in the Bodleian Libary at Oxford; besides, the Hebrew text provided by J.Chr. Wagenseil in his Tela Ignea Satanae (1681) dwelt on a Strassburg manuscript nowadays lost
The Time Has Come for Targeted Therapies for AML: Lights and Shadows
No full textAcute myeloid leukemia (AML) is a complex disease characterized by genetic and clinical heterogeneity and high mortality. After 40 years during which the standard of care for patients evolved very little, the therapeutic landscape has recently seen rapid changes, with the approval of eight new drugs by the Food and Drug Administration (FDA) within the last 2 years, providing new opportunities, as well as new challenges, for treating clinicians. These therapies include FLT3 inhibitors midostaurin and gilteritinib, CPX-351 (liposomal cytarabine and daunorubicin), gemtuzumab ozogamicin (GO, anti-CD33 monoclonal antibody conjugated with calicheamicin), IDH1/IDH2 inhibitors ivosidenib and enasidenib, Hedgehog inhibitor glasdegib, and BCL-2 inhibitor venetoclax. In this review, we summarize currently available data on these new drugs and discuss the rapidly evolving therapeutic armamentarium for AML, focusing on targeted therapies
Determination of Arsenic, Cadmium, Cobalt, Chromium, Nickel, and Lead in Cosmetic Face-Powders: Optimization of Extraction and Validation.
No full textL'Equity based crowdfunding e la c.d. «dematerializzazione» delle quote di s.r.l.
No full textEquity based crowdfunding
and the “dematerializzazione” of private companies’ shares.
The d.l. 24 January 2015, n. 3 (so-called Investment Compact) has introduced a new share transfer system in private companies (Italian s.r.l.) which have the qualification of “start-up innovative” or the qualification of “PMI innovative”. This new system is based on the financial intermediaries’ activity, under the control of Consob, and allows the private companies with these qualifications to easily transfer their shares during an operation of equity based crowdfunding. This system is projected as an alternative to the ordinary rules related to the transfer of private companies’ shares, as it permits the transfer of shares without the typical legal obligations in regard to the “Registro delle Imprese” (the Italian Commerce register). The new rules aim to simplify business bureaucracy and to create better conditions for the growth of a secondary market of the shares. In this analysis the author will weigh up the multifaceted problems in the coordination between the new rules and the general system of the Italian private companies (s.r.l.) and scrutinize the effectiveness of the new rules, specifically the possibility that a sensible secondary market will be created due to the new alternative system
L’amministrazione delle società di persone tra continuità e rinnovamento: questioni aperte e prospettive evolutive
No full textIl contributo offre una dettagliata analisi della disciplina dell’amministrazione nelle società di persone, ponendola in relazione con le trasformazioni che hanno interessato il diritto dell’impresa, tra la tradizionale flessibilità propria delle società di persone e le esigenze connesse all’adeguatezza degli assetti organizzativi. Dopo aver ricostruito l’evoluzione sto-rica della figura dell’amministratore, l’A. si sofferma sulle tensioni interpretative emerse in seguito ai mutamenti del contesto economico-sociale e all’introduzione di norme soprav-venute al codice civile. Punto di partenza dell’indagine è il rapporto problematico tra la tradizionale agilità strutturale delle società di persone e la crescente centralità dei profili organizzativi, che impongono di dotare la società di un “assetto strutturato e coerente”, funzionale al raggiungimento di quegli standard di “serietà imprenditoriale e correttezza” già evocati dai progetti di riforma Di Sabato e Rovelli. L’esame si articola attorno a diversi profili, tra cui il riparto di competenze tra soci e amministratori, i limiti al potere di rappre-sentanza derivanti dall’oggetto sociale, i doveri di informazione e l’emersione di tratti pro-pri delle società di capitali. Tali ambiti sono accomunati da incertezze applicative e tensio-ni ermeneutiche che richiedono una rielaborazione sistematica aggiornata e coerente. In questo quadro si inserisce anche il tema, tanto discusso quanto attuale, dell’ammissibilità della figura dell’amministratore non socio: una possibilità oggi teoricamente sostenibile al-la luce dell’evoluzione normativa e comparatistica, ma che richiede, de iure condendo, una disciplina organica e puntuale. Tale disciplina dovrebbe riguardare, in particolare, i profili connessi alla revoca degli amministratori e alla loro responsabilità verso i creditori sociali, in un equilibrio rinnovato che valorizzi al contempo la storica flessibilità del modello per-sonalistico e la sempre più marcata rilevanza dei profili relativi all’organizzazione interna.This article provides an in-depth analysis of the rules governing management in partner-ships, framing it within the broader transformations that have affected business law. It highlights the tension between the original flexibility characteristic of partnership and the increasingly pressing regulatory requirements aimed at ensuring adequate organizational structures. After tracing the historical evolution of the role of the directors, the author fo-cuses on the interpretive tensions that have emerged in the wake of changes in the socio-economic context and the introduction of provisions adopted after the civil Code. The in-quiry begins with the problematic relationship between the traditional structural agility of partnerships and the growing centrality of organizational elements. This shift demands that firms be equipped with a “structured and coherent” framework designed to meet those standards of “entrepreneurial seriousness and propriety” already evoked by the Di Sabato and Rovelli reform proposals. The discussion addresses several key issues, including the allocation of powers between partners and directors, the limits on representational author-ity imposed by the company’s purpose, duties of disclosure, and the emergence of traits characteristic of corporations. All these areas are marked by uncertainties in application and interpretative tensions that call for a coherent and up-to-date systematic reconsidera-tion. Against this backdrop, the article also examines the much-debated and timely ques-tion of whether a non-partner can serve as a director–a possibility that is now theoretically tenable considering legislative and comparative developments, but one that, de iure condendo, still requires a comprehensive and precise regulatory framework. Such a framework should address issues relating to the removal of directors and their liability to-wards the partnership’s creditors, within a renewed balance that gives due weight to both the model’s historic flexibility and the increasingly marked importance of organizational arrangements
Prise d’espace ? Patriarcat, féminisme et transgression autour de Con il vento nei capelli de Salwa Salem
No full textThis article is aimed on the analysis of Con il vento nei capelli (“With the wind in one’s head”), an autobiography of Salwa Salem that is among the first works of migrant literature in Italy.
The interesting point of this autobiography is the space of autonomy and of identity, as it is perceived by the novel’s author. This search for private space is placed, as we’ll try to proof, in between the tradition and modernity, patriarchal living and feminism, the choice that the author has to make between staying at home and migrating elsewher
Low-dose Gemtuzumab-Ozogamicin as post-consolidation therapy in elderly patients with acute myeloid leukaemia: a pilot study.
No full textThe incidence of acute myeloid leukemia (AML) increases with
advancing age, and in older patients the chance of cure has not
substantially improved recently. In the elderly the incidence of
secondary AML is high, and is often associated with both high-
risk cytogenetic abnormalities and expression of the multidrug
resistance protein (MDR1) and p-glycoprotein (p-gp), both of
which are associated with poor outcomes (Appelbaum et al,
2006).
Gemtuzumab-Ozogamicin (GO) is a humanized anti-CD33
monoclonal antibody conjugated to Calicheamicin that is
rapidly internalized after binding to CD33. GO seems to be
more selective than conventional chemotherapy, as CD33 is
expressed on AML cells but not in normal haematopoietic
stem cells (SCs) or in non-haematopoietic tissues (Sievers et al,
2001). In a series of phase II studies including 142 patients
with AML in first relapse, GO monotherapy was associated
with a 30% overall complete remission (CR) rate, including a
26% rate in patients over 60 years of age (Sievers et al, 2001;
Larson et al, 2002). These results led to US Food and Drug
Administration approval of GO for the treatment of patients
over 60 years with relapsed AML (Bross et al, 2001). As a
consequence of these results, there is interest in extending the
use of GO to a frontline treatment for AML in combination
with conventional chemotherapy.
Little is known about the usefulness of GO as consolidation
and/or maintenance therapy, and no data on the topic have
been published to date. In particular, there are no data
concerning the safety and efficacy of GO in the setting of
post-consolidation therapy in AML patients except for a short
report concerning the effects after autologous stem cell
transplantation (ASCT) (Cascavilla et al, 2008). GO mono-
therapy has typically been administered as a 2-h infusion at a
dose of 9 mg/m2 on days 1 and 15 of treatment, but the
administration of fractionated doses has recently been reported
to have a better safety profile (Taksin et al, 2007).
We evaluated the efficacy of low-dose GO as late
consolidation therapy after CR in a subset of fit elderly
patients who were enrolled in a prospective study. From June
1999 to December 2007, 125 patients of 60 years of age or
older with morphologically-confirmed AML and non-acute
promyelocytic leukaemia were observed in our institution. The
preliminary results from 42 patients were reported in 2007
(Olivieri et al, 2007). Fit patients, selected according to
previously published inclusion criteria (Olivieri et al, 2007),
were treated with intensive chemotherapy, followed by SC
mobilization and ASCT (Olivieri et al, 2007). Patients who
successfully mobilized SCs underwent ASCT, while poor
mobilisers received a further consolidation including standard
chemotherapy or investigational immunotherapy with GO.
Among the initial 125 patients, 79 fulfilled the inclusion
criteria; of those, 56 (72Æ1%) achieved CR, and 52 received the
first intensive consolidation course followed by G-CSF to
collect SC for ASCT. In cases of mobilisation failure, patients
were allowed to chose between an experimental approach
B J H 8 1 6 8 B Dispatch: 8.3.10 Journal: BJH CE: Varun Kumar
Journal Name Manuscript No. Author Received: No. of pages: 3 PE: Subhashree
Table I. Clinical and biological characteristics of the three groups of
patients receiving consolidation with GO (A), ASCT (B), Chemo-
therapy (CHT) (C) and Allogeneic Transplantation (D).
A (%) B (%) C (%) D (%) P
Gender
Male 8 (62) 8 (42Æ1) 3 (50) 3 (60) N.S.
Female 5 (38) 11 (57Æ9) 3 (50) 2 (40)
Age (years)
Median = 70 (range, 61–76)
£70 7 (54) 10 (52Æ6) 5 (83Æ3) 4 (80) N.S.
>70 6 (46) 9 (47Æ4) 1 (16Æ7) 1 (20)
FAB subtype
M0 0 5 (26Æ5) 0 0 N.S.
M1 3 (23) 4 (21) 2 (33Æ3) 2 (40)
M2 3 (23) 8 (42) 4 (66Æ7) 2 (40)
M4 3 (23) 2 (10Æ5) 0 1 (20)
M5 3 (23) 0 0 0
M6 1 (8) 0 0 0
M7 0 0 0 0
Leucocytosis (·109/l)
WBC <10 8 (61Æ5) 9 (47Æ4) 4 (66Æ7) 4 (80) N.S.
WBC 10–50 5 (38Æ5) 6 (31Æ6) 1 (16Æ7) 1 (20)
WBC >50 0 4 (21) 1 (16Æ7) 0
Karyotype
Poor 2 (15Æ4) 7(36Æ8) 1 (16Æ7) 4 (80) N.S.
Intermediate 6 (46Æ2) 8 (42Æ1) 4 (66Æ7) 0
Favourable 2 (15Æ4) 0 1 (16Æ7) 1 (20)
NE 3 (15Æ4) 4 (21Æ1) 0 0
Secondary disease*
Yes 3 (23) 8 (42) 2 (33Æ3) 1 (20) N.S.
No 10 (77) 11 (58) 4 (66Æ7) 4 (80)
FAB, French-American-British classification; NE, not evaluated; WBC,
white blood cell.
*To chemotherapy or Myelodysplastic Syndrome.
correspondence
a 2010 Blackwell Publishing Ltd, British Journal of Haematology doi:10.1111/j.1365-2141.2010.08168.x
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including low-dose GO or a further conventional consolidation
course. GO was administered on a compassionate basis, and the
costs were charged to our department. Among the 52 patients
who received intensive consolidation, two died and seven
relapsed; thus, 43 patients were evaluable for post-remission
treatment after the SC mobilization attempt. Of those, 19
patients (44%) successfully mobilized SC and received ASCT.
Of the 24 that did not mobilise SC, 13 received GO, six patients
refused GO and received a second consolidation with chemo-
therapy, and five patients received reduced intensity
conditioning allogeneic transplant from sibling donors.
The current analysis did not include all patients receiving
allogeneic transplant because of the poor prognosis of the
disease. The disease characteristics of the remaining patients
were equally distributed in the three groups, and the data are
shown in Table I.
All the patients received GO at a dose of 3 mg/m2 three
times monthly on an outpatient basis and received common
antimicrobial prophylaxis. No patients needed hospitalisation
for infections or other major toxicities; the median duration of
neutropenia (PMN <0Æ5 · 109/l) after GO was 12 d (range
0–33 d). The main toxicities (World Health Organization
grade III–IV) were myelosuppression (n = 9), hypertransam-
inasaemia (n = 1) and anaphylaxis (n = 3); no major unex-
pected adverse events were observed. With a median follow up
of 58 months (range 19–89), a total of 15 patients were alive
and in CR: five received ASCT (median follow-up 77 months,
range 45-89), nine received GO (median follow-up 38 months,
range: 19–75 months), and one, who received chemotherapy,
has been followed for 72 months. Two patients receiving GO
relapsed and eventually died after 13 and 19 months from CR
after the first consolidation. Two more patients relapsed after
15 and 32 months after a second CR after salvage chemother-
apy, followed by three doses of GO 3 mg/m2 administered as
consolidation therapy.
In conclusion, nine of the 13 patients who received GO as
late consolidation therapy were alive and in continuous CR
(including two patients with secondary AML and two with a
complex karyotype). The Landmark survival analysis showed
better overall survival (OS) and disease-free survival (DFS)
(P = 0Æ017 and 0Æ01 respectively) in the 13 patients that
received GO (5-year OS, 60%; 5-year DFS, 67%) compared
with patients that received either ASCT (5-year OS and DFS:
26%) or chemotherapy (5-year OS and DFS: 17%) (Fig 1).
Our preliminary data support a potential role for low-dose
GO in consolidation therapy in elderly patients with AML
who are able to achieve CR after intensive induction. Late
consolidation with low-dose GO seems to be safe and easily
manageable; the myelosuppression was relevant, but generally
short. All patients received the 3 GO infusions on an
outpatient basis without further readmissions and without
fatal events.
These preliminary data encourage the use of low-dose GO as
late consolidation therapy to eliminate the minimal residual
disease (MRD) in older patients with AML. Larger studies are
needed for confirmation, possibly including monitoring of
MRD during treatment. It also remains to be established if SC
collection failure after CR represents an independent favour-
able prognostic factor in AML patients, as suggested by some
retrospective data (Keating et al, 2003).
Antonella Poloni1
Debora Capelli1
Silvia Trappolini1
Benedetta Costantini1
Mauro Montanari1
Guido Gini1
Ilaria Scortechini1
Giorgia Mancini1
Giancarlo Discepoli2
Pietro Leoni1
Attilio Olivieri3
1Dipartimento di Scienze Mediche e Chirurgiche, Sezione di Ematologia,
Universita` Politecnica delle Marche and Azienda Ospedaliera Ospedali
Riuniti, 2Laboratorio di Citogenetica e Genetica Molecolare, Clinica di
Pediatria, Ospedali Riuniti, Ancona, and 3Azienda Ospedaliera San
Carlo, Potenza, Italy.
E-mail: [email protected]
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80
100
0 12 24 36 48 60 72 84 96
Cumulative probability (%)
Months
OS
GO
ASCT
CHT
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20
40
60
80
100
0 12 24 36 48 60 72 84 96
Cumulative probability (%)
Months
DFS
Fig 1. Comparison of the outcome (OS and DFS) of patients receiving late consolidation with Gemtuzumab-Ozogamicin (GO), autologous stem cell
transplantation (ASCT) or chemotherapy (CHT) (log rank test).
Correspondence
2 a 2010 Blackwell Publishing Ltd, British Journal of Haematology
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References
Appelbaum, F.R., Gundacker, H., Head, D.R., Slovak, M.L., Willman,
C.L., Godwin, J.E., Anderson, J.E. & Petersdorf, S.H. (2006) Age and
acute myeloid leukaemia. Blood, 107, 3481–3485.
Bross, P.F., Beitz, J., Chen, G., Chen, X.H., Duffy, E., Kieffer, L., Roy,
S., Sridhara, R., Rahman, A., Williams, G. & Pazdur, R. (2001)
Approval summary: gemtuzumab ozogamicin in relapsed acute
myeloid leukemia. Clinical Cancer Research, 7, 1490–1496.
Cascavilla, N., D’Arena, G., Greco, M.M., Melillo, L., Merla, E. &
Carella, A.M. (2008) Gemtuzumab-Ozogamicin as maintenance
therapy after Autologous Stem Cell Transplantation in elderly
patients with Acute Myeloid Leukaemia. British Journal of Haematology
, 142, 852–853.
Keating, S., Suciu, S., de Witte, T., Zittoun, R., Mandelli, F., Belhabri,
A., Amadori, S., Fibbe, W., Gallo, E., Fillet, G., Varet, B., Meloni, G.,
Hagemeijer, A., Fazi, P., Solbu, G., Willemze, R., EORTC Leukemia
Group & GIMEMA Leukemia Group. (2003) The stem cell
mobilizing capacity of patients with acute myeloid leukemia in
complete remission correlates with relapse risk: results of EORTC-
GIMEMA AML 10 trial. Leukemia, 17, 60–67.
Larson, R.A., Boogaerts, M., Estey, E., Karanes, C., Stadtmauer, E.A.,
Sievers, E.L., Mineur, P., Bennett, J.M., Berger, M.S., Eten, C.B.,
Munteanu, M., Loken, M.R., Van Dongen, J.J., Bernstein, I.D.,
Appelbaum, F.R. & Mylotarg Study Group. (2002) Antibody-
targeted chemotherapy of older patients with acute myeloid
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Leukemia, 16, 1627–1636.
Olivieri, A., Capelli, D., Troiani, D., Poloni, A., Montanari, M.,
Offidani, M., Discepoli, G. & Leoni, P. (2007) A new intensive
induction schedule, including high-dose Idarubicin, high-dose
Aracytin and Amifostine, in older AML patients: feasibility and
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M.L., Berger, M.S., Eten, C.B., Loken, M.R., Van Dongen, J.J.,
Bernstein, I.D., Appelbaum, F.R. & Mylotarg Study Group. (2001)
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Keywords: AML, chemotherapy,
Feasibility and Outcome of a Phase II Study of Intensive Induction Chemotherapy in 91 Elderly Patients with AML Evaluated Using a Simplified Multidimensional Geriatric Assessment
No full textIntroduction: We prospectively tested in a phase II study high-dose aracytin and idarubicin plus amifostine as induction regimen in 149 patients with acute myeloid leukaemia (AML) aged ≥ 60 years, evaluated by a simplified multidimensional geriatric assessment (MGA).
Methods: Ninety-one fully or partially fit patients (61%) were allocated to intensive chemotherapy and 58 (39%) frail patients to best supportive care (BSC). Intensively treated patients, showing early death and complete response (CR) rate respectively of 5.5% and 73.6%, received 61 consolidations, followed by autologous transplant (ASCT), stem cell transplantation (SCT) or gemtuzumab ozogamicin, depending on mobilization outcome and donor availability.
Results: The 8-year overall survival (OS) of these patients was 20.4%, with median duration of 11.4 months significantly superior to the 1.5 months of BSC arm (p < 0.001). Hyperleukocytosis and cytogenetics were predictors of survival with a relative risk of 1.8 in patients with poor karyotype without hyperleukocytosis (p = 0.02) and 3 in those with hyperleukocytosis (≥ 50,000/μl) (p = 0.002).
Conclusion: MGA allowed tailored post-consolidation in 53.8% of patients after high-dose aracytin induction, with long-term survival doubling that reported in the literature after standard-dose cytarabine regimens
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