39 research outputs found
Selected essays of Henk F. Moed
No full textThis part presents a collection of the most important publications by Henk F. Moed. This collection characterises the author as a researcher personality with a broad spectrum of activities and a multifaceted research profile. As Henk Moed has contributed to the advancement of the field in many topics, an overview of the development of his career is, to a considerable extent, also a survey of the research field. We grouped his publications into seven topics in the field at the intersection of bibliometrics, informetrics, science studies and research assessment. The main topics are the following
Monitoring Chronic Myeloid Leukemia: How Molecular Tools May Drive Therapeutic Approaches
No full textMore than 15 years ago, imatinib entered into the clinical practice as a "magic bullet"; from that point on, the prognosis of patients affected by chronic myeloid leukemia (CML) became comparable to that of aged-matched healthy subjects. The aims of treatment with tyrosine kinase inhibitors (TKIs) are for complete hematological response after 3 months of treatment, complete cytogenetic response after 6 months, and a reduction of the molecular disease of at least 3 logs after 12 months. Patients who do not reach their goal can switch to another TKI. Thus, the molecular monitoring of response is the main consideration of management of CML patients. Moreover, cases in deep and persistent molecular response can tempt the physician to interrupt treatment, and this "dream" is possible due to the quantitative PCR. After great international effort, today the BCR-ABL1 expression obtained in each laboratory is standardized and expressed as "international scale." This aim has been reached after the establishment of the EUTOS program (in Europe) and the LabNet network (in Italy), the platforms where biologists meet clinicians. In the field of quantitative PCR, the digital PCR is now a new and promising, sensitive and accurate tool. Some authors reported that digital PCR is able to better classify patients in precise "molecular classes," which could lead to a better identification of those cases that will benefit from the interruption of therapy. In addition, digital PCR can be used to identify a point mutation in the ABL1 domain, mutations that are often responsible for the TKI resistance. In the field of resistance, a prominent role is played by the NGS that enables identification of any mutation in ABL1 domain, even at sub-clonal levels. This manuscript reviews how the molecular tools can lead the management of CML patients, focusing on the more recent technical advances
Combining Directional Distances and ELECTRE Multicriteria Decision Analysis for Preferable Assessments of Efficiency
No full textTraditional nonparametric frontier models used to asses technical, allocative, cost, and scale efficiencies, based on Data Envelopment Analysis (DEA), reflect not only the most favorable way of weighing outputs over inputs but also tradeoffs of compensations among the many production possibilities. When managers or policy makers have an explicit preference over some production resources or products, such tradeoffs and the resulting estimated efficiency measure may not represent the most appropriate scenario of evaluation. The good performance of some decision units on some production variables may offset the bad performance on others, and this may be sufficient to qualify such decision units as efficient (or less inefficient) in most DEA rankings, but not under the subjective perspective of the decision maker. This is particularly important in the case of non-discretionary inputs, bad outputs, or less desirable production configurations. In this chapter, we discuss this issue offering a perspective on how we can advance in this avenue by developing multicriteria non-compensatory directions for the expansion of outputs or contraction of inputs. A numerical example is reported at the end of this discussion. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG
CALR-positive myeloproliferative disorder in a patient with Ph-positive chronic myeloid leukemia in durable treatment-free remission: a case report
No full textCurrent diagnostic criteria for Philadelphia-negative myeloproliferative neoplasia (MPN) have been redefined by the discovery of Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL) and calreticulin (CALR) genetic alterations. Only few cases of coexistence of CALR-mutated MPN and Philadelphia-positive chronic myeloid leukemia (CML) have been described so far. Here we report the case of a patient with CML diagnosed in 2001, treated with imatinib and pegylated interferon (IFN) frontline. She reached complete molecular remission (CMR) and discontinued imatinib, maintaining treatment free remission. Due to persistent thrombocytosis, we repeated bone marrow (BM) analysis and diagnosed CARL-mutated essential thrombocythemia (ET). A CALR-positive clone was found to be present since 2001, and was unaffected by imatinib treatment, possibly representing a molecular abnormality arising at stem cell level
Treatment-free remission in Chronic Myeloid Leukemia harboring atypical BCR-ABL1 transcripts.
No full textDiscontinuation of tyrosine kinase inhibitors (TKI) is the main goal today in the field of Philadelphia positive chronic myeloid leukemia (Ph + CML) and the criteria to attempt the interruption of therapy are well defined and rely on the possibility to regularly monitor the BCR-ABL1 transcript. Patients harboring atypical transcripts are automatically excluded from protocols due to the absence of a standardized method of quantification of their minimal residual disease (MRD). We report here the outcome of 6 patients with atypical transcripts with a long follow up whose MRD was followed in three cases with digital PCR during their treatment free remission (TFR)
Mechanical modeling of the bandgap response of tensegrity metamaterials
No full textWe investigate the acoustic band structure of tensegrity mass-spring chains as a function of the applied, local and global states of prestress. We first study the bandgap response of linear monoatomic chains, which show lumped masses connected to tensegrity prisms acting as mechanical springs. Next, we present a numerical study on the nonlinear wave dynamics of the examined systems in the geometrically nonlinear regime that is induced by the presence of moderately large relative displacements between the lumped masses. Such a study confirms the results of the linear analysis in the case of an elastically hardening system. © 2019 Author(s)
Evaluation of Cepheid Xpert® BCR-ABL Monitor Assay in Three Italian Reference Centers for Monitoring of BCR-ABL Transcript Levels in CML Patients
No full textEffective management of tyrosine kinase inhibitor (TKI) therapy for patients with CML requires frequent patient testing to monitor patient disease status. The gold standard for this testing is a PCR measurement of the BCR-ABL/ABL transcript ratio. Hence, standardized, accurate and reproducible molecular analyses are fundamental for clinicians in order to correctly address therapeutic decision and to achieve a better patient management. Based on these clinical needs, it is widely recognized that inter-laboratory reproducibility is a crucial issue that requires standardization and strict alignment of BCR-ABL values on the international scale (IS), as established by the International Randomized Study of Interferon and STI571 (IRIS) laboratories. In addition to this, another important aspect in terms of patient management is the availability of a rapid response, improving patient quality of life by reducing anxiety linked to delay in results delivery.
Xpert® BCR-ABL Monitor, developed and manufactured by Cepheid (Sunnyvale, CA), is a cartridge-based automated assay for quantification of BCR-ABL1 mRNA, reporting results in International Scale (IS). Alignment to the IS, based upon the quality control standards derived from the WHO BCR-ABL Standards, is performed lot to lot automatically by the software of the Cepheid GeneXpert® DX Instrument.
Xpert® BCR-ABL Monitor automates and integrates sample processing, nucleic acids extraction and amplification and target sequence detection in peripheral blood specimens collected either in EDTA or PAXgene tubes using real-time RT-PCR. The cartridge includes reagents to detect BCR-ABL fusion genes resulting from two major breakpoints, translocation e13a2 (b2a2) and e14a2 (b3a2) and the ABL transcript as an endogenous control.
In the following study, Xpert® BCR-ABL Monitor was independently evaluated in the three Italian reference centers for BCR-ABL mRNA monitoring of the LabNet project. A total of 150 peripheral blood samples from CML patients, equally divided between centers, were analyzed both with the standard laboratory method and with Xpert® BCR-ABL Monitor Assay, in order to compare the results expressed in International Scale. BCR-ABL mRNA of the specimens covered a broad IS range, allowing to compare data also at low levels of disease (MR 4.5, 0.00316% BCR-ABL/ABL).
Overall, linear regression demonstrated that there was a good correlation between Xpert® BCR-ABL Monitor and reference centers data (R2= 0.92). Correlation slightly increased when the data produced with Xpert® BCR-ABL Monitor were refined using a correction tool not automatically adopted by the current version of the assay software (R2= 0.93). Moreover, using assay comparison criteria proposed by Müller et al. (Leukemia 2009), Xpert® BCR-ABL Monitor was considered comparable to the standard laboratory methods of the reference centers, considering that all the three acceptance criteria were satisfied (58% of the samples between 0.5 and 2-fold variation, 78% of the samples between 0.33 and 3-fold variation, 91% of the samples between 0.2 and 5-fold variation).
In conclusion, Xpert® BCR-ABL Monitor demonstrated to be a rapid, reliable and accurate test for monitoring of BCR-ABL mRNA transcript levels. Results were available within approximately 2 hours, potentially allowing clinicians to report results to patient the same day of the visit. From the technical point of view, cartridge-based automated system significantly reduced operator hands-on time from several hours to approximately 15 minutes.
Concerning the assay comparative performance, Xpert® BCR-ABL showed to have a good inter-laboratory reproducibility, with no significant differences between the three reference centers standard methods
Second-Generation Tyrosine Kinase Inhibitors Can Induce Complete Molecular Response in Ph-Positive Acute Lymphoblastic Leukemia After Allogeneic Stem Cell Transplant
No full textGrowth hormone (GH)‐induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome.
No full textClin Endocrinol (Oxf). 2004 Oct;61(4):437-40.
Growth hormone (GH)-induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome.
Porto G, Cruz E, Miranda HP, Porto B, Vasconcelos JC, Lacerda R, Roetto A, Daraio F, Bacelar C.
Santo António General Hospital, Porto, Portugal. [email protected]
Abstract
This paper describes a rare case of Turner's syndrome associated with Juvenile Haemochromatosis and severe lymphopenia, followed-up for a period of 5 years. Because of the indication for treatment with growth hormone (GH), this case was observed as a model to analyse the effects of GH on growth, iron mobilization and lymphocyte reconstitution. For this purpose, a serial study of the T lymphocyte subpopulations CD4+, CD8+, CD8+ CD28+ and CD8+ CD28- was performed by immunophenotyping during the follow-up period. Besides the impact of both phlebotomy treatment and GH on the rapid growth and mobilization of 20.8 g of iron in 136 weeks, the most relevant observation was the finding of a significant expansion of CD8+ T lymphocytes expressing the costimulatory marker CD28 in the setting of the severe lymphopenia. These findings constitute new clinical evidence supporting the notion that the GH/IGF-1 system has an important role on the maintenance of T cell homeostasis in vivo, and that GH may be regarded as a putative therapeutic agent in T lymphocyte reconstitution.
PMID: 15473875 [PubMed - indexed for MEDLINE
One Step Quantitative Molecular Approach for Detection of BCR/ABL Translocation and for Monitoring and Follow up of the Minimal Residual Disease in CML Patients Under Tyrosine Kines Inhibitors Treatment.
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