ABSTRACT
ABSTRACT: A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Adult , Humans , Prednisone/adverse effects , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Dexamethasone , Platelet Count , Disease-Free SurvivalABSTRACT
This comment presents Maria Montessori (1870-1952) and highlights that her child-centered method of education is based on brilliant intuitions, which were confirmed by neuroscience research many decades later, such as the distinction of three critical periods in children's psychobiological development; the importance of the environment in supporting cerebral development and in promoting learning, as well as of affective stimulation in psychological growth and maturation; the specific neural structure of humans that specifically enables the acquisition of a language; the vital role of fine object manipulation in neuropsychological development, and of the physical exercise in brain and nervous system development.
Subject(s)
Brain/physiology , Child Development/physiology , Language/history , Learning/physiology , Child , Female , History, 19th Century , History, 20th Century , Humans , Neurosciences/historyABSTRACT
The use of generic drugs after patent expiration of their originators is a relative novelty in the treatment of chronic cancer patients in Western countries. In this observational study we analyzed a cohort of 294 Italian chronic phase chronic myeloid leukemia patients treated frontline with branded imatinib (Glivec®) for at least 6 months and then uniformly switched to generic imatinib upon requirement of health authorities in early 2017. Median age at diagnosis was 57 years (range 19-87). Sokal risk was low/intermediate/high in 55%, 32% and 8% of cases, respectively. Median duration of branded imatinib treatment was 7.4 years (range 0.5-16.7). At a median follow-up of 7.5 months after switch to generic imatinib, 17% of patients reported new or worsening side effects, but grade 3-4 non-hematological adverse events were rare. Six patients switched back to branded imatinib, with improvement in the side effect profile, and 4 pts moved to bosutinib or nilotinib for resistance/intolerance. The majority of patients were in major (26%) or deep molecular response (66%) at the time of switch. Molecular responses remained stable, improved or worsened in 61%, 25% and 14% of patients, respectively. We conclude that switch to generic imatinib for patients who have been receiving branded imatinib appears to be effective and safe. Molecular responses may continue to improve over time. Some patients experienced new or worsened side effects but less than 5% of the whole cohort needed to switch back to branded imatinib or move to other treatments. Savings were around 3 million Euros.
Subject(s)
Drugs, Generic/administration & dosage , Imatinib Mesylate/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Adult , Aged , Aged, 80 and over , Drugs, Generic/adverse effects , Female , Follow-Up Studies , Humans , Imatinib Mesylate/adverse effects , Italy/epidemiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Time FactorsABSTRACT
Most patients affected by chronic lymphocytic leukemia are diagnosed by flow cytometry. Several immunophenotypic markers have been identified as significant and independent prognostic variables, especially from retrospective cohorts. However, while attractive because their detection is inexpensive and feasible in most laboratories, only few have been validated by independent series. The expression of leukocyte-associated immunoglobulin-like receptor-1 (also known as LAIR1, LAIR-1 or CD305), an inhibitor of B-cell receptor-mediated signaling, has been reported to be lacking in high-risk chronic lymphocytic leukemia. However, its correlation with biological variables and its prognostic significance remain unknown. We investigated 311 consecutive patients, prospectively enrolled since 2007. Methods for studying patients were standardized and included clinical assessment, immunophenotype, fluorescence in situ hybridization, and status of immunoglobulin heavy chain variable region genes. Overall, 22.1% of patients had Binet stage B or C disease, 38.5% had unmutated immunoglobulin genes, 15.1% had high-risk cytogenetic abnormalities, 23.4% were CD38(+), 37.8% CD49d(+), and 59.8% LAIR1(+). Expression of LAIR1 was inversely related to that of CD38 (P=0.0005), but was not associated with CD49d expression (P=0.96). A significantly lower expression of LAIR1 was observed in patients with Binet stage B or C disease (P=0.023), and in the presence of high-risk cytogenetic abnormalities (P=0.048) or unmutated immunoglobulin heavy chain variable region genes (P<0.0001). At univariate analysis LAIR1(+) was significantly associated with longer time to first treatment (P=0.0002). This favorable effect of LAIR1(+) was confirmed by multivariate analysis (hazard ratio=2.1, P=0.03 for LAIR1). Our results indicate that LAIR1 expression is a reliable and inexpensive marker capable of independently predicting time to first treatment in newly diagnosed unselected patients with chronic lymphocytic leukemia.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Receptors, Immunologic/metabolism , Adult , Aged , Aged, 80 and over , Chromosome Aberrations , Disease Progression , Female , Flow Cytometry , Follow-Up Studies , Gene Expression , Humans , Immunoglobulin Heavy Chains/genetics , Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Mutation , Neoplasm Staging , Patient Outcome Assessment , Prognosis , Prospective Studies , Receptors, Immunologic/geneticsABSTRACT
The oxygen sensing pathway modulates erythropoietin expression. In normal cells, intracellular oxygen tensions are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins. PHD2 isozyme has a key role in tagging hypoxia-inducible factor (HIF)-α subunits for polyubiquitination and proteasomal degradation. Erythrocytosis-associated PHD2 mutations reduce hydroxylation of HIF-α. The investigation of 67 patients with isolated erythrocytosis, either sporadic or familial, allowed the identification of three novel mutations in the catalytic domain of the PHD2 protein. All new mutations are germ-line, heterozygous and missense, and code for a predicted full length mutant PHD2 protein. Identification of the disease-causing genes will be of critical importance for a better classification of familial and acquired erythrocytosis, offering additional insight into the erythropoietin regulating oxygen sensing pathway.
Subject(s)
Germ-Line Mutation , Polycythemia/genetics , Procollagen-Proline Dioxygenase/genetics , Adult , Amino Acid Substitution , Base Sequence , Heterozygote , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases , Male , Middle Aged , Models, Molecular , Procollagen-Proline Dioxygenase/chemistry , Protein ConformationSubject(s)
Cerebral Cortex/physiology , Cognition/physiology , Neurosciences/history , Brain Mapping , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , History, Ancient , History, Medieval , Human Characteristics , Humans , Models, NeurologicalABSTRACT
The treatment of polycythemia vera in young adults is challenging, requiring one to run a balance between the increased risk of vascular complications, if left untreated, versus the potential of promoting secondary leukemia/myelodysplasia or cancer, if actively managed with chemotherapy. We report the results of a 20-year retrospective analysis in a cohort of 30 young adults with PV (median age 37 years, range 19-45) treated exclusively with phlebotomy, aspirin and hydroxyurea only in case of vascular complications occurring in the presence of thrombocytosis (platelet count > 600 × 10(9)/L). With this approach, vascular complications were no higher than in other published series, and secondary leukemia/myelodysplasia or cancer was not observed during a follow-up of 14 years.
Subject(s)
Aspirin/therapeutic use , Fibrinolytic Agents/therapeutic use , Janus Kinase 2/genetics , Phlebotomy , Polycythemia Vera/drug therapy , Thrombosis/prevention & control , Adult , Antineoplastic Agents/therapeutic use , Cohort Studies , Combined Modality Therapy , Disease Progression , Female , Humans , Hydroxyurea/therapeutic use , Male , Middle Aged , Polycythemia Vera/complications , Retrospective Studies , Thrombosis/etiology , Young AdultABSTRACT
The De purgantium medicamentorum facultate is a short pharmacological polemic work, written by Galen against the Asclepiades' and Erasitratus' thought about a supposed attractive power of evacuating pharmaka. The work is an important contribution to the defence of Hippocratic humoralism. The article deals with a Latin translation of the Galenic text from Greek, earlier dating than Niccolò da Reggio's ones, examining the autenticity and dating, the Greek and Latin translation, the Greek texts and its medioeval tradition.
Subject(s)
Manuscripts, Medical as Topic/history , Cathartics/history , History, Medieval , Italy , Language , Pharmacology/historyABSTRACT
The article deals with the history of medical thermalism in the Italian region Marche. Therapeutical uses of water is well known in Greek and Roman medicine; the most ancient text devoted to a medical possible use of natural waters is Airs, Waters and Places by Hippocrates. The author examines the history of Marchigian baths, according to the testimony of Andrea Bacci in his De thermis, quoted in the Roman editon of 1622.
Subject(s)
Balneology/history , History, 15th Century , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, Ancient , History, Medieval , ItalyABSTRACT
Clinical definitions and terminology vary greatly in clinical studies on idiopathic thrombocytopenic purpura (ITP). An objective assessment of this heterogeneity may be of interest, providing a basis for standardizing ITP terminology. A systematic review of the recent literature on ITP in adults was carried out. The following items were extracted from the articles for comparison: platelet count cut-off values to decide treatment and type of response; timing for evaluating the response to treatment; evaluation of bleeding symptoms; criteria to define initial, chronic and refractory forms. A total of 79 papers, among those published or referenced from 2000 to 2006, were considered eligible. No consensus among the different authors was found on several issues, including:platelet count for definition of ITP; grading of severity; definition of chronic ITP; platelet threshold to start treatment; platelet count to define response to treatment and timing for evaluating the response to therapy. There was only major consensus for the length of disease duration required to diagnose chronic ITP, the criteria for splenectomy and the definition of refractory ITP. Confusing terminology and an unacceptable heterogeneity of clinical definitions used for management decisions and to describe outcomes were evident in recent ITP literature. This makes it very difficult to compare different studies and to share data and clinical experiences. A standardization of terminology and definitions used in ITP is urgently needed.
Subject(s)
Blood Platelets/cytology , Hematology/methods , Purpura, Thrombocytopenic, Idiopathic/classification , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Adult , Chronic Disease , Diagnosis, Differential , Humans , Immunoglobulins, Intravenous/therapeutic use , Middle Aged , Platelet Count , Prognosis , Risk , Splenectomy/methods , Terminology as Topic , Treatment OutcomeABSTRACT
Peter of Abano translated from Greek at least six works of Galen. These translations did not widely circulate either in manuscripts or printed editions. The previous Latin translations from Arabic were preferred in the University medical teaching, and the successive translations from Greek by Niccolò of Reggio obscured the ones by Peter of Abano. Moreover, the Greek sources used by Peter of Abano do not seem to belong to a tradition different from that of the preserved manuscripts. Nevertheless, Peter of Abano stands out as an original investigator of Greek medical texts.
Subject(s)
History of Medicine , Language , Manuscripts, Medical as Topic/history , Translations , Greek World , History, Ancient , History, Medieval , Humans , ItalyABSTRACT
We have carried out a literature review on diagnosis and treatment of idiopathic thrombocytopenic purpura (ITP) in adults, based on the articles published during the years 2000-2005, aimed at assessing the variability in the terminology and clinical definitions. A total of 85 articles were considered eligible. In particular, the platelet level for initiating treatment, the definition of response to treatment in terms of platelet count and timing, the evaluation of bleeding symptoms, the criteria to define chronic and refractory forms were compared in the different articles. The study revealed confounding terminology and an unacceptable heterogeneity for clinical definitions relevant to management decisions and outcomes reporting.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Terminology as Topic , Adult , Humans , Platelet Count , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/therapy , Severity of Illness Index , Time FactorsABSTRACT
This article provides an examination of the Latin complete editions of Galen, from 1490 to 1528, which are not all pointed out and described by Richard Durling in his census published in 1961, in the Journal of the Warburg and Courtauld Institutes. They present the first large circulation of Galen in the Renassaince, which was in Latin, not in Greek, as well as the constitution of the Galenic corpus. At first it was formed by Medieval translations. The humanistic translations, often of the same known texts, were printed from the edition by Pietro Antonio Rustico in 1515-16; they occupy a separate volume in both the editions of 1528, and the two supplementary volumes of the Giuntine of 1528, printed in 1531 and 1533.
Subject(s)
Rare Books/history , Catalogs as Topic , History, 15th Century , History, 16th Century , ItalyABSTRACT
During the Modern Age, in the Marche, in the Pontifical State, it was possible to study medicine and to obtain a degree in medicine in Macerata, Fermo, Urbino, Camerino and Fano. In these cities, from the end of the XVII century to the beginning of the XIX century, public libraries were founded also to support academic teaching. Private collections of medical books, generally formed in Rome, arrived in the Marche to increase the newborn public libraries. In 1720 Pope Clemens XI founded a public library in the monastery of Saint Francis in Urbino. In this library the medical books were bequeathed by the famous Roman physician Giovanni Maria Lancisi. The present article provides the first results of a research, which aims at identifying Lancisi's medical books.