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PURPOSE: To evaluate the retinal vessel density (VD) with optical coherence tomography angiography (OCTA) in asymptomatic patients affected by Waldenström macroglobulinemia (WM) without hyperviscosity syndrome (HVS) and to highlight the presence of microvascular damage in theese clinically asymptomatic WD patients. DESIGN: Prospective study. METHODS: A total of 43 eyes from 43 WM patients (24 females, 19 males, mean age 55.1 ± 13.6 years) were enrolled from January 2023 to December 2023 in the Eye Clinic of the University of Naples Federico II. Along with WM patients, 40 healthy subjects (HS) (20 females, 20 males, mean age 52.3 ± 15.6 years) with a normal ophthalmic examination and no history of intraocular surgery or retinal pathologic features were included as control group All patients and controls underwent OCTA RESULTS: The two groups were not significantly different for age and sex Visual acuity examination showed no statistically significant difference in BCVA between controls and patients Compared to HS, WD patients showed lower VD values in the SCP in the whole image (47.95 ± 5.17% vs. 52.99 ± 2.52 %; p < 0.001), as well as in the parafovea (53.01 ± 6.69% vs. 55.30 ± 2.61 %; p = 0.002), and fovea (21.38 ± 9.01% vs. 30.31 ± 5.84 %; p < 0.0001). On the other hand, in the DCP VD values were significantly higher in patients compared to controls in the whole image (55.82 ± 8.07% vs. 50.83 ± 5.46 %; p = 0.005), as well as in the parafovea (56.76 ± 6.26% vs. 52.59 ± 5.46 %; p = 0.0001), and fovea (38.75 ± 8.59% vs. 33.43 ± 8.68 %; p < 0.0001). CONCLUSION: The finding that OCTA confirmed the presence of widespread microvascular damage in WD patients clinically silent. Thus, OCTA is a safe rapid imaging technique that could represent a valid biomarker of systemic vascular dysfunction.
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OBJECTIVES: Erythropoiesis-stimulating agents (ESA) have an established role in treating anemia in hematological malignancies. However, their role, particularly biosimilar ESA (B-ESA), in myelofibrosis (MF) is not well established. METHODS: This study retrospectively collected data on 96 MF patients treated with B-ESA (alpha/zeta) for the management of anemia to assess safety, efficacy (anemia response [AR]), and survival. RESULTS: Seventy-seven patients (80%) obtained AR. The median time to AR was 2.5 months. In multivariate analysis, significant predictive factors of AR were transfusion independency (p = .006) and ferritin levels <200 ng/ml (p = .009) at baseline. After a median follow-up of 43.8 months from diagnosis, 38 patients (39%) died, 11 (28.9%) from leukemic evolution. Only two patients (2.5%) stopped B-ESA for toxicity. The 24-month survival was significantly affected by response to B-ESA (70.8% in AR vs. 55.3% in non-responder patients, p = .016). In multivariate analysis, age ≤ 70 years (p = .029) and Hb > 8.5 g/dl (p = .047) at baseline were significantly associated with improved survival, with a trend for longer survival in AR patients (p = .06). CONCLUSIONS: B-ESA seems to be an effective and well-tolerated option for anemia treatment in the MF setting. This strategy deserves further clinical investigation.
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Anemia , Biosimilares Farmacéuticos , Hematínicos , Mielofibrosis Primaria , Humanos , Anciano , Hematínicos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Eritropoyesis , Estudios Retrospectivos , Mielofibrosis Primaria/tratamiento farmacológico , Anemia/tratamiento farmacológico , HemoglobinasRESUMEN
Foetal spleen is described as a transient focus of haematopoiesis between the 3rd and 5th month of gestation: this function is however entirely replaced by the bone marrow before the end of pregnancy. This study identifies haematopoiesis in foetal spleen by exploring changes of echogenicity during its development throughout gestation. Two intervals of pregnancy were studied: Mid-Pregnancy (Mid-P, 19-23 weeks) and End-Pregnancy (End-P, 37-41 weeks). The foetal spleen was investigated in 80 pregnant women (41 vs 39). Due to quality criteria the comparison was made between 60 images (30 Mid-P vs 30 End-P). The acquisition of splenic parenchyma was followed by clustering segmentation. We identified two new parameters resulted from the clustering segmentation: Dark Ratio (DR) and Light Ratio (LR). These are related to splenic echogenicity expressing the percentage of dark and light signal in the clustered image, influenced by blood cellularity. The mean of DR value was different among the 2 groups (0.0631 vs 0.0483, P = 0.014), while LR did not show any significant differences. We conclude that DR may represent a reliable radiomic parameter in the determination of extramedullary haematopoiesis in the spleen.
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Polycythemia vera (PV) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) characterized by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow, mainly due to a Janus kinase 2 gene mutation (JAK2V617F). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2V617F cell growth, has demonstrated good efficacy and safety in three phase 1/2 studies in patients with PV. This manuscript focuses on the 4-year mean (2.8 year median) follow-up of an open-label, long-term study that enrolled 51 patients with PV (out of a total of 54 with MPN) who received clinical benefit from givinostat in these previous studies or on compassionate use, and who continued to receive givinostat at the last effective and tolerated dose. The primary objectives are to determine givinostat's long-term safety and tolerability, and efficacy evaluated by the investigators according to internationally recognized response criteria. During follow-up, only 10% of PV patients reported Grade 3 treatment-related adverse events (AEs), while none had Grade 4 or 5 treatment-related AEs. The overall response rate for the duration of follow-up was always greater than 80% in patients with PV. In conclusion, givinostat demonstrated a good safety and efficacy profile in patients with PV, data supporting long-term use in this population.
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Carbamatos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Adulto , Anciano , Carbamatos/efectos adversos , Femenino , Estudios de Seguimiento , Inhibidores de Histona Desacetilasas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out. The immunological analysis included extended B-cell immunophenotyping, evaluation of class switch recombination and somatic hypermutation, and next generation sequencing (NGS). Recurrent or severe infections and chronic lung changes at the diagnosis were reported in five out of six and two out of six patients, respectively. Five out of six patients showed signs of lymphoproliferation and four patients developed malignancies. Four patients showed impaired B-cell homeostasis. Class switch recombination was functional in vivo in all patients. NGS revealed, in one case, a pathogenic mutation in PIK3R1. In a second case, the ITPKB gene, implicated in B- and T-cell development, survival, and activity was identified as a potential candidate gene. Independent of the genetic basis, very high IgM levels represent a risk factor for the development of recurrent infections leading to chronic lung changes, lymphoproliferation, and high risk of malignancies.
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Bone marrow aspiration and biopsy (BMAB) is a painful procedure, and the routinely used local infiltration anesthesia (LIA) with lidocaine is unable to provide pain relief during the most uncomfortable phases. The primary endpoint of the present randomized, patient-blinded trial was to evaluate the efficacy of an opioid and benzodiazepine combination plus LIA (sedoanalgesia) in patients undergoing BMAB for hematological malignancies. The secondary endpoint was the safety of the procedure in an outpatient setting. Ancillary assessments were anticipatory anxiety related to pain recall in the event of re-biopsy, and adequacy of bone tissue harvested. Patients were randomly assigned to one of 2 arms to receive either sedoanalgesic placebo plus LIA (standard group) or oral fentanyl citrate 200 µg plus oral midazolam 5 mg plus LIA (combo group) during BMAB. Pre-procedural anxiety and procedural pain were assessed according to the Numerical Rating Scale (NRS: 0-10), dividing the time of the procedure into five intervals (T0, T1, T2a, T2b and T3) and evaluating the degree of discomfort at each time (T) in both groups. One hundred and sixteen patients were eligible for the study. At T2b (time of biopsy) and T3 (time after biopsy), a significantly lower perception of pain was registered in the combo group. Moreover, there were no significant sedoanalgesia-related side-effects. Finally, histological specimens were higher in quality in the combo group. Sedoanalgesia was highly effective in reducing pain during biopsy, diminished anticipatory anxiety in patients undergoing re-biopsy and led to fewer non-diagnostic specimens being harvested.
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Cytarabine, the 4-amino-1-(ß-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.
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Citarabina/química , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/química , Antimetabolitos Antineoplásicos/economía , Cromatografía Líquida de Alta Presión , Ahorro de Costo , Citarabina/administración & dosificación , Citarabina/economía , Costos de los Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Cumplimiento de la Medicación , Resonancia Magnética Nuclear Biomolecular/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Soluciones/químicaRESUMEN
Ruxolitinib is the only commercially available JAK1/2 inhibitor approved for the treatment of myelofibrosis-related splenomegaly and symptoms. During treatment, as rare conditions, leukocytosis and/or thrombocytosis could develop and the management of these situations is not well established. We report here 53 myelofibrosis patients that received a combination of hydroxyurea and ruxolitinib because of uncontrolled myeloproliferation. Both drugs were administered outside clinical trials. At 48 weeks, a significant reduction in leucocyte and platelet counts was observed (p = 0.02 and p = 0.04, respectively). Additionally, the spleen volume decreased from a median value of 10 cm below the left costal margin (range, 0-10) to 6 cm (range, 0-15). The rate of spleen response increased from 14% at the start of the combination to 45% after 48 weeks. The safety profile of the combination was consistent with that observed with ruxolitinib single agent. These data require further confirmation in large cohorts of patients prospectively assessed.
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Plaquetas/efectos de los fármacos , Hidroxiurea/uso terapéutico , Leucocitos/efectos de los fármacos , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Esplenomegalia/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Plaquetas/patología , Recuento de Células , Proliferación Celular/efectos de los fármacos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Leucocitos/patología , Masculino , Persona de Mediana Edad , Nitrilos , Seguridad del Paciente , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/patología , Pirimidinas , Estudios Retrospectivos , Esplenomegalia/complicaciones , Esplenomegalia/mortalidad , Esplenomegalia/patología , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Ruxolitinib, an orally bioavailable and selective inhibitor of Janus kinase 1 (JAK1) and JAK2, significantly reduces splenomegaly and disease-related symptoms in patients with myelofibrosis (MF). However, no clear survival benefit has been demonstrated, which may in part reflect suboptimal drug exposure related to lower dosages needed to minimize hematological toxicity, specifically cytopenias. Furthermore, the optimal management of specific conditions such as leukocytosis or thrombocytosis in patients under ruxolitinib therapy is still undefined. In these cases, combining ruxolitinib with a cytoreductive agent like hydroxyurea might improve hematological response. This observational multi-center study enrolled 20 adult patients with intermediate- or high-risk primary MF, post- polycythemia vera MF, or postessential thrombocythemia MF with hyperproliferative manifestations of the disease and WBC and/or platelet counts not controlled by ruxolitinib therapy. The patients received treatment with a combination of ruxolitinib and hydroxyurea. A clinical response of any type was obtained in 8 patients (40%) during ruxolitinib monotherapy and in 17 patients (85%) during ruxolitinib-hydroxyurea combination (P = 0.003). After a median duration of 12.4 months of combination therapy, 16/20 patients had a hematological response; 14/17 patients who had started combination therapy to control WBC count and 2/3 who started in order to reduce platelets count. The number of patients requiring ruxolitinib dosage reduction or discontinuations was lower during combination therapy and, at the end of follow-up the median ruxolitinib dose was increased in 50% of patients. In conclusion, the combination of hydroxyurea with ruxolitinib yielded a high clinical response rate and increased ruxolitinib exposure in patients with hyperproliferative forms of MF.
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Hidroxiurea/uso terapéutico , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Biomarcadores , Quimioterapia Combinada , Femenino , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Inhibidores de las Cinasas Janus/administración & dosificación , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Masculino , Persona de Mediana Edad , Nitrilos , Mielofibrosis Primaria/metabolismo , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirimidinas , Estudios RetrospectivosRESUMEN
Essentials The BCR-ABL negative myeloproliferative neoplasms are subjected to unknown phenotypic modifiers. GATA-1 is upregulated in ET patients, regardless of treatment regimen or mutational status. Myelofibrosis (MF) megakaryocytes displayed decreased GATA-1 staining. GATA-1 may have utility as a diagnostic marker in ET and in its differential diagnosis from MF. ABSTRACT: Background The BCR-ABL-negative myeloproliferative neoplasms, i.e., polycythemia vera, essential thrombocythemia (ET), and myelofibrosis (MF), are characterized by mutations in JAK2, CALR, or MPL. However, an as yet unknown factor drives the precise disease phenotype. The hematopoietic transcription factor GATA-1 and its downstream targets NFE2 and FLI1 are responsible for determining erythroid and megakaryocyte lineages during hematopoietic stem cell differentiation. Previous studies have demonstrated a low level of GATA-1 expression in megakaryocytes from patients with MF. Objectives and methods The expression of GATA-1, NFE2 and FLI1 was studied for changes in the peripheral blood (PB) of ET patients. Peripheral blood samples were obtained from 36 ET patients, 14 MF patients, and seven healthy control donors. Total RNA from PB mononuclear cells (PBMCs) was extracted, and quantitative polymerase chain reaction was used to determine relative changes in gene expression. Protein levels of GATA-1 were also determined in bone marrow sections from ET and MF patients. Results GATA-1 mRNA was upregulated in ET patients, regardless of treatment regimen or mutational status. FLI1 expression was significantly downregulated, whereas NFE2 expression was unaffected by changes in GATA-1 mRNA levels. Megakaryocytes from ET patients showed increased protein levels of GATA-1 as compared with those from MF patients. Conclusions Our results confirmed, in PB, our previous data demonstrating elevated levels of GATA-1 mRNA in total bone marrow of ET patients. GATA-1 mRNA levels are independent of cytoreductive therapies, and may have utility as a diagnostic marker in ET and in its differential diagnosis from MF.
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Factor de Transcripción GATA1/metabolismo , Mielofibrosis Primaria/diagnóstico , Trombocitemia Esencial/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Médula Ósea/metabolismo , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Factor de Transcripción GATA1/genética , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Subunidad p45 del Factor de Transcripción NF-E2/genética , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/metabolismo , Proteína Proto-Oncogénica c-fli-1/genética , ARN Mensajero/sangre , ARN Mensajero/genética , Trombocitemia Esencial/genética , Trombocitemia Esencial/metabolismoRESUMEN
Erythropoiesis-stimulating agents (ESAs) were combined with ruxolitinib in 59 anaemic myelofibrosis patients (93% with Dynamic International Prognostic Scoring System [DIPSS] intermediate-2/high risk; 52·5% transfusion-dependent). Anaemia response (AR) rate was 54% and 76% of patients responded at 5 years. A further 15% displayed minor improvement in anaemia and 78% of patients reduced spleen size. Endogenous erythropoietin levels <125 u/l correlated with a higher AR rate (63% vs. 20%, P = 0·008). No thrombotic events or other toxicities occurred. Overall survival was 62% at 4 years, influenced by DIPSS and transfusion dependency. ESAs seem effective in improving anaemia in ruxruxolitinib-treated myelofibrosis patients.
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Anemia/tratamiento farmacológico , Manejo de la Enfermedad , Hematínicos/uso terapéutico , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Anemia/etiología , Transfusión Sanguínea , Humanos , Nitrilos , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/mortalidad , Pirazoles/efectos adversos , Pirimidinas , Bazo/patología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Renal impairment (RI) is a relevant complication of patients affected by multiple myeloma (MM); it can be present in up to 30-35% of newly diagnosed MM and is linked to a poor outcome. However, early recognition and early treatment with novel agents can overcome the negative impact of RI and even reverse kidney damage in most cases. Lenalidomide, available as an oral compound, is an immunomodulatory drug with both antiproliferative and immunomodulatory activity that is largely used in the management of MM. Dose reduction is mandatory in RI; however, there is no theoretical assumption against the possibility that protracting the time of full standard doses can be equally effective and tolerated by patients requiring reduced doses. In this report, we describe our retrospective experience, in 18 patients, with the administration of lenalidomide 25 mg every other day for patients with MM and RI. The overall response ratio was 66.5%. More than half (61.1%) of the patients had a renal response. The median progression-free survival was 8 months (range: 3-18 months). No serious adverse event occurred during treatment, and it was never necessary to disrupt or delay treatment for toxicity. These preliminary observations point to a significant therapeutic effect of lenalidomide, at the dose of 25 mg every other day for 21 days, with logistic and economic advantages. However, these results should be validated by controlled studies involving larger numbers of patients.
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Factores Inmunológicos/uso terapéutico , Inmunomodulación , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Insuficiencia Renal/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Lenalidomida/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/inmunología , Supervivencia sin Progresión , Insuficiencia Renal/etiología , Estudios RetrospectivosRESUMEN
A 56-year-old man developed disseminate lymphadenopathies, associated with hepato-splenomegaly, fever, nocturnal sweating and weight loss. Imaging studies in particular FDG-PET/CT raised the suspicion of a malignant disease. But blood flow cytometry assay for B/T cell clonality was negative and fine-needle biopsy of enlarged laterocervical lymph node showed a not specific "reactive hyperplasia". Four months later, the patient developed a non-itching rash; since a further anamnestic investigation revealed an history of high-risk sexual intercourse, the patient underwent serological tests for Treponema pallidum that were positive at high titer, after a first negative screening. Made the diagnosis of secondary syphilis, the patient responded to the treatment with benzyl penicillin with complete resolution of symptoms. This case highlights the importance of carefully screening the patients with suspected lymphoadenopathies also for lue, particularly in presence of behavioral risk factors.
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Enfermedades Pulmonares/diagnóstico , Sífilis/diagnóstico , Antibacterianos/uso terapéutico , Diagnóstico Diferencial , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sífilis/diagnóstico por imagen , Sífilis/tratamiento farmacológicoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Transfusión Sanguínea , Caquexia/prevención & control , Hidroxiurea/administración & dosificación , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/administración & dosificación , Esplenomegalia/tratamiento farmacológico , Caquexia/etiología , Esquema de Medicación , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Mielofibrosis Primaria/complicaciones , Pirimidinas , Esplenomegalia/etiologíaRESUMEN
In patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), the anti-thrombotic and/or cytoreductive treatment in the follow-up may affect the evaluation of the pro-thrombotic weight of the clinical and biological characteristics at diagnosis. In order to avoid this potential confounding effect, we investigated the relationship between prior thrombosis (PrTh: thrombosis occurred before diagnosis and before treatment) and the characteristics at diagnosis in 977 thrombocythemic patients with MPN, reclassified according to the WHO 2008 criteria. PrTh occurred in 194 (19.9%) patients, with similar rates in the different MPNs. In multivariate analysis, PrTh rate was significantly related to minor thrombocytosis (platelets ≤700×10(9)/L), leukocytosis (leukocytes >10×10(9)/L), higher hematocrit (HCT >45%), JAK2 V617F mutation, older age, and cardiovascular risk factors (CVRFs). The highest PrTh rate (33.9%) was associated with the coexistence of minor thrombocytosis and leukocytosis. Of note, the inverse relationship between PrTh rate and platelet count is consistent with the hemostatic paradox of thrombocytosis. In conclusion, this analysis in MPN patients disclosed the unbiased characteristics at diagnosis with a pro-thrombotic effect. Moreover, it suggests that the optimal control of blood cells counts, and CVRFs might be of utmost importance in the prevention of thrombosis during the follow-up.
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Trastornos Mieloproliferativos/complicaciones , Trombocitosis/complicaciones , Trombofilia/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Leucocitosis , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/diagnóstico , Recuento de Plaquetas , Factores de Riesgo , Trombosis/prevención & control , Adulto JovenRESUMEN
Givinostat, a histone-deacetylase inhibitor (HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms (MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera (PV), unresponsive to the maximum tolerated doses (MTD) of hydroxycarbamide (HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients.
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Carbamatos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Hidroxiurea/uso terapéutico , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carbamatos/administración & dosificación , Carbamatos/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Inhibidores de Histona Desacetilasas/administración & dosificación , Inhibidores de Histona Desacetilasas/efectos adversos , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Masculino , Persona de Mediana Edad , Inhibidores de la Síntesis del Ácido Nucleico/administración & dosificación , Inhibidores de la Síntesis del Ácido Nucleico/efectos adversos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
The prevalence and causes of erythrocytosis after liver transplantation have never been studied, even though this condition is known to predispose patients to thrombosis leading to graft failure or death. Erythrocytosis after orthotopic liver transplantation (OLT) can be defined as an increase in the red cell mass >125% in patients without a pre-OLT history of this condition. The study population was composed of 96 patients: 33 had undergone transplantation for a hepatitis B virus (HBV) infection (18 had a hepatitis D virus coinfection), 43 had undergone transplantation for a hepatitis C virus infection, 9 had undergone transplantation for alcohol abuse, and 11 had undergone transplantation for other causes [autoimmune liver disease (6), Wilson's syndrome (1), or cryptogenetic liver cirrhosis (4)]. Idiopathic erythrocytosis was reported in 11 male patients with a history of HBV infection. Patients with the diagnosis of erythrocytosis underwent phlebotomy every 3 weeks until the hematocrit level reached 45%, and this was repeated if the level exceeded 49%, so no patient presented with cardiovascular accidents during the follow-up. In conclusion, a history of HBV infection, male sex, and hepatitis B immune globulin therapy are all possible cofactors for an increased risk of erythrocytosis in OLT patients.
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Hospitales Universitarios , Trasplante de Hígado/efectos adversos , Policitemia/etiología , Adyuvantes Inmunológicos/efectos adversos , Adulto , Anciano , Femenino , Hematócrito , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Humanos , Inmunoglobulinas/efectos adversos , Italia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Flebotomía , Policitemia/sangre , Policitemia/diagnóstico , Policitemia/terapia , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoRESUMEN
Hydroxyurea (Hydroxycarbamide; HU) is commonly used for the long-term treatment of patients with Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPNs). It is considered a first-choice agent for the treatment of these disorders as underlined by the European Leukemia Net Consensus Conference [1], although it is formally approved for this indication in some countries only. The drug is reportedly well tolerated in the large majority of subjects, although systemic and/or localized toxicities have been reported. Consensus criteria for definition of "intolerance" to HU have been described;patients who develop intolerance are candidate for second-line therapy and, more recently, for investigational drugs. However, no epidemiologic information about the occurrence of the most clinically significant HU-associated adverse events is yet available. In this study, the authors report on a multicenter series of 3,411 patients who were treated with HU among which 184, accounting for 5% of total, developed significant drug-related toxicities. These data provide an estimate of the frequency and a detailed characterization of clinically significant HU-related toxicities; these information have relevance for the management of MPN patients who require second-line therapy after developing HU-related intolerance.
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Antimetabolitos/efectos adversos , Erupciones por Medicamentos/etiología , Fiebre/inducido químicamente , Hidroxiurea/efectos adversos , Trastornos Mieloproliferativos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos/uso terapéutico , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma de Células Escamosas/epidemiología , Erupciones por Medicamentos/epidemiología , Femenino , Fiebre/epidemiología , Humanos , Hidroxiurea/uso terapéutico , Queratosis Actínica/inducido químicamente , Queratosis Actínica/epidemiología , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Neumonía/epidemiología , Neumonía/etiología , Estudios Retrospectivos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiología , Úlcera Cutánea/inducido químicamente , Úlcera Cutánea/epidemiología , Adulto JovenRESUMEN
This retrospective study of the thrombocythemia Italian registry (RIT) documented that 71 (30.6%) out of 232 ET patients experienced 88 cardiovascular adverse events (CV-AEs) during anagrelide treatment (522 pt-y). The rate of CV-AEs was: 24.1% for palpitations, 4.3% for angina, 3.5% for arterial hypertension, 3.0% for congestive heart failure, 1.8% for arrhythmia, 0.9% for AMI, 0.4% for pericardial effusion. CV-AEs led to treatment discontinuation in nine (3.9%) patients, while in the remaining cases they were managed by pharmacological intervention and/or patient life style improvement. CV-AEs had no relationship with patient characteristics (including older age). A significant relationship was found only with a higher anagrelide induction dose. In the absence of any agreed protocol, a cardiovascular instrumental evaluation (CV-IE) was performed in 102 (44%) patients before commencement of anagrelide (with higher rate after the anagrelide/Xagrid EMA approval of 2004), and in 84 (36%) patients during treatment. Patients with and without CV-IEs, who resulted completely balanced for all their characteristics, did not significantly differ in the occurrence of CV-AEs. In conclusion, this study on ET patients treated with anagrelide shows that CV-AEs, equally distributed in younger and older subjects, were mostly mild and easily manageable, allowing safe treatment continuation in the majority of cases. Moreover, routinely performing a CV-IE did not appear to anticipate the occurrence of CV-AEs.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Trombocitemia Esencial/tratamiento farmacológico , Trombocitemia Esencial/epidemiología , Privación de Tratamiento/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/inducido químicamente , Niño , Estudios de Cohortes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inducido químicamente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Quinazolinas/administración & dosificación , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The recent evolution of nursing management of cardiovascular disease has led to significant changes in specific healthcare processes. The aim of this study is to present the first nursing survey of Italian intensive cardiac care units (ICCUs). METHODS: In March and April 2007, a questionnaire investigating the main problems concerning ICCU organization, specifically addressed to nursing care, has been mailed to all the operative Italian ICCUs. The questionnaire investigated staff characteristics, education and training, daily work organization, risk management strategies, and nursing research. RESULTS: For a more detailed analysis, the ICCUs were divided into three levels (standard, medium and high) based on their technological equipment, and in particular mechanical ventilatory assistance and intra-aortic balloon pumping availability. A high proportion of ICCUs (347/385, 90%) answered to the questionnaire and an analysis of the responses revealed no significant differences between the three main geographical areas of Italy (North, Center, South). CONCLUSIONS: Despite some organizational and staffing problems, the survey confirmed the high level of routine nursing care, the strong tendency towards the integration of different professional competencies among the staff, and the high degree of standardization.