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1.
Br J Haematol ; 185(4): 733-742, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30836432

RESUMEN

Multi-factorial causes jeopardize brain integrity in ß-thalassaemia. Intracranial parenchymal and vascular changes have been reported among young ß-thalassaemia patients but conventional magnetic resonance imaging (MRI) findings are contradictory making early MRI and magnetic resonance angiography (MRA)/venography monitoring a matter of debate. This study prospectively investigated 75 neurologically asymptomatic ß-thalassaemia patients (mean-age 35·2 ± 10·7 years; 52/75 transfusion-dependent; 41/75 splenectomised) using a 3T magnetic resonance scanner; clinical, laboratory and treatment data were also collected. White matter ischaemic-like abnormalities, intracranial artery stenoses, aneurysms and sinus venous thrombosis were compared between patients and 56 healthy controls (mean-age 33·9 ± 10·8 years). No patient or control showed silent territorial or lacunar strokes, intracranial artery stenoses or signs of sinus thrombosis. White matter lesions were found both in patients (35/75, 46·7%) and controls (28/56, 50·0%), without differences in terms of number (4·0 ± 10·6 vs. 4·6 ± 9·1, P = 0·63), size and Fazekas' Score. Intracranial aneurysms did not differ between patients and controls for incidence rate (7/75, 9·3% vs. 5/56, 8·9%), size and site. Vascular and parenchymal abnormality rate did not differ according to treatments or clinical phenotype. According to this study, asymptomatic ß-thalassaemia patients treated according to current guidelines do not seem to carry an increased risk of brain and intracranial vascular changes, thus weakening recommendations for regular brain MRI monitoring.


Asunto(s)
Isquemia Encefálica/patología , Encéfalo/irrigación sanguínea , Enfermedades del Sistema Nervioso/patología , Talasemia beta/patología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Humanos , Aneurisma Intracraneal/patología , Leucoencefalopatías/patología , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estudios Prospectivos , Sustancia Blanca/irrigación sanguínea , Adulto Joven
2.
Am J Hematol ; 94(3): 312-318, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30489651

RESUMEN

The management of iron overload in thalassemia has changed dramatically since the implementation of magnetic resonance imaging, which allows detection of preclinical iron overload and prevention of clinical complications. This study evaluated the effect of deferasirox (DFX), the newest once-daily oral chelator, on cardiac function, iron overload and cardiovascular events over a longer follow up in a "real world" setting. Longitudinal changes in cardiac magnetic resonance T2*, cardiac function parameters and cardiovascular clinical events were assessed in a cohort of 98 TM patients exposed to DFX for a mean of 6.9 years (range 1.8-11.6 years). No cardiac death or incident heart failure occurred. Cardiac T2* significantly increased (+2.6 ± 11.9 msec; P = 0.035) in the whole population, with a significantly greater increase (+11.6 ± 15.5 msec, P = 0.019) in patients with cardiac iron overload (T2* <20 ms). A significant improvement in left-ventricular ejection fraction (LVEF) (from 50.6 ± 6 to 60.2 ± 5; P = 0.001) was observed in 11 (84.6%) out of 13 patients who normalized cardiac function (LVEF >56%). Arrhythmias were the most frequent cardiac adverse event noted but none led to DFX discontinuation. Our data indicate that DFX is effective in maintaining cardiac iron level in the normal range and in improving cardiac iron overload. No heart failure or cardiac death was reported over this longer observation up to 12 years. For the first time, a DFX-induced improvement in LVEF was observed in a subgroup of patients with abnormal cardiac function at baseline, a preliminary observation which deserves further evaluation.


Asunto(s)
Arritmias Cardíacas/prevención & control , Deferasirox/uso terapéutico , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/terapia , Talasemia beta/terapia , Arritmias Cardíacas/diagnóstico por imagen , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Transfusión Sanguínea/métodos , Niño , Preescolar , Manejo de la Enfermedad , Femenino , Humanos , Lactante , Sobrecarga de Hierro/diagnóstico por imagen , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/fisiopatología , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Volumen Sistólico , Resultado del Tratamiento , Talasemia beta/complicaciones , Talasemia beta/diagnóstico por imagen , Talasemia beta/fisiopatología
3.
Br J Haematol ; 167(1): 121-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24992281

RESUMEN

The risk of developing hepatocellular carcinoma (HCC) in patients with thalassaemia is increased by transfusion-transmitted infections and haemosiderosis. All Italian Thalassaemia Centres use an ad hoc form to report all diagnoses of HCC to the Italian Registry. Since our last report, in 2002, up to December 2012, 62 new cases were identified, 52% of whom were affected by thalassaemia major (TM) and 45% by thalassaemia intermedia (TI). Two had sickle-thalassaemia (ST). The incidence of the tumour is increasing, possibly because of the longer survival of patients and consequent longer exposure to the noxious effects of the hepatotropic viruses and iron. Three patients were hepatitis B surface antigen-positive, 36 patients showed evidence of past infection with hepatitis B virus (HBV). Fifty-four patients had antibodies against hepatitis C virus (HCV), 43 of whom were HCV RNA positive. Only 4 had no evidence of exposure either to HCV or HBV. The mean liver iron concentration was 8 mg/g dry weight. Therapy included chemoembolization, thermoablation with radiofrequency and surgical excision. Three patients underwent liver transplant, 21 received palliative therapy. As of December 2012, 41 patients had died. The average survival time from HCC detection to death was 11·5 months (1·4-107·2 months). Ultrasonography is recommended every 6 months to enable early diagnosis of HCC, which is crucial to decrease mortality.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Talasemia/complicaciones , Adulto , Anciano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Comorbilidad , Femenino , Ferritinas/sangre , Humanos , Hierro/metabolismo , Italia , Estimación de Kaplan-Meier , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Prevalencia , Sistema de Registros , Talasemia/sangre , Resultado del Tratamiento
4.
Am J Hematol ; 89(12): 1102-6, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25197009

RESUMEN

Iron overload in ß-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n = 5) and hypoparathyroidism (n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased (P = 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre-exisisting was observed in a real clinical practice setting.


Asunto(s)
Benzoatos/uso terapéutico , Terapia por Quelación , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Osteoporosis/prevención & control , Triazoles/uso terapéutico , Talasemia beta/tratamiento farmacológico , Adolescente , Adulto , Densidad Ósea , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Calcio/administración & dosificación , Niño , Preescolar , Deferasirox , Diabetes Mellitus/etiología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Diabetes Mellitus/prevención & control , Difosfonatos/uso terapéutico , Femenino , Humanos , Hipogonadismo/etiología , Hipogonadismo/metabolismo , Hipogonadismo/patología , Hipogonadismo/prevención & control , Hipoparatiroidismo/etiología , Hipoparatiroidismo/metabolismo , Hipoparatiroidismo/patología , Hipoparatiroidismo/prevención & control , Hipotiroidismo/etiología , Hipotiroidismo/metabolismo , Hipotiroidismo/patología , Hipotiroidismo/prevención & control , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/patología , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Osteoporosis/metabolismo , Osteoporosis/patología , Pubertad Tardía/etiología , Pubertad Tardía/metabolismo , Pubertad Tardía/patología , Pubertad Tardía/prevención & control , Estudios Retrospectivos , Vitamina D/administración & dosificación , Talasemia beta/complicaciones , Talasemia beta/metabolismo , Talasemia beta/patología
5.
Open Biol ; 14(2): 230319, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38350611

RESUMEN

Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1S). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1S, we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1S. These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1S levels.


Asunto(s)
Síndrome de Down , Leucemia Mieloide , Reacción Leucemoide , MicroARNs , Humanos , Síndrome de Down/genética , Síndrome de Down/complicaciones , Síndrome de Down/patología , Leucemia Mieloide/genética , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patología , Reacción Leucemoide/complicaciones , MicroARNs/genética , MicroARNs/metabolismo
6.
Blood ; 117(24): 6673-80, 2011 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-21467542

RESUMEN

Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal dominant thrombocytopenia and only 2 families were known. However, we recently identified mutations in the 5'-untranslated region of the ANKRD26 gene in 9 THC2 families. Here we report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. Because THC2 affected 21 of the 210 families in our database, it has to be considered one of the less rare forms of inherited thrombocytopenia. Analysis of all 21 families with ANKRD26 mutations identified to date revealed that thrombocytopenia and bleeding tendency were usually mild. Nearly all patients had no platelet macrocytosis, and this characteristic distinguishes THC2 from most other forms of inherited thrombocytopenia. In the majority of cases, platelets were deficient in glycoprotein Ia and α-granules, whereas in vitro platelet aggregation was normal. Bone marrow examination and serum thrombopoietin levels suggested that thrombocytopenia was derived from dysmegakaryopoiesis. Unexplained high values of hemoglobin and leukocytes were observed in a few cases. An unexpected finding that warrants further investigation was a high incidence of acute leukemia. Given the scarcity of distinctive characteristics, the ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias.


Asunto(s)
Familia , Trombocitopenia/genética , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Repetición de Anquirina/genética , Niño , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Humanos , Patrón de Herencia/genética , Masculino , Persona de Mediana Edad , Mutación/fisiología , Linaje , Factores de Transcripción/fisiología , Adulto Joven
8.
J Chemother ; 34(8): 524-533, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35570742

RESUMEN

Skin and soft tissue infections (SSTIs) represent a heterogenous group of pathological conditions involving the skin or the underlying subcutaneous tissues, fascia and muscle, characterised by a considerable variety of clinical presentations, severity and possible aetiological pathogens. Although previous analyses on restricted types of SSTIs and population have already been published, we conducted a large nationwide surveillance program on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients and their management. Twenty-nine Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. We included in our database all cases managed by ID specialists participating to the study, independently from their severity or the setting of consultation. Here, we integrated previous preliminary results analysing and reporting data referring to a 3-year period (October 2016-October 2019). During this period, the study population included 478 adult patients with diagnosis of SSTI. The type of infection diagnosed, the aetiological agent involved and some notes on antimicrobial susceptibilities were collected and reported herein. We also analysed the most common co-morbidities, the type and duration of therapy executed, before and after ID intervention and the length of stay. The results of our study provide information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.


Asunto(s)
Infecciones de los Tejidos Blandos , Adulto , Humanos , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/epidemiología , Infecciones de los Tejidos Blandos/etiología , Estudios Prospectivos , Sistema de Registros , Comorbilidad , Italia/epidemiología , Antibacterianos/uso terapéutico
9.
Pediatr Blood Cancer ; 56(2): 273-8, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20830773

RESUMEN

BACKGROUND: The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series. PROCEDURE: Children from 16 centers in Italy, who were less than 18 years of age and diagnosed with chronic ITP (cITP), were screened for H. pylori infection. Positive patients underwent standard triple therapy with amoxicillin, clarithromycin, and omeprazole. The eradication response was defined as follows: complete response, platelet (PLT) count ≥ 150 × 10(9) /L; partial response, PLT count of at least 50 × 10(9) /L; no response, PLT count <50 × 10(9) /L. RESULTS: Of 244 screened patients, 50 (20%) had H. pylori infection, 37 of which received eradication therapy and completed follow-up. Eradication was successful in 33/37 patients (89%). PLT recovery was demonstrated in 13/33 patients after eradication (39%), whereas spontaneous remission was observed in 17/166 (10%) H. pylori-negative patients (P < 0.005). Responders more often required second line eradication (9/13), whereas a second cycle was required in 3/20 non-responders (P < 0.005). CONCLUSIONS: Among the large cohort of patients, those who underwent successful H. pylori eradication showed a significantly higher PLT response. Therefore, it may be appropriate to look for H. pylori and eventually eradicate it in children with cITP.


Asunto(s)
Plaquetas/efectos de los fármacos , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/microbiología , Adolescente , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Niño , Enfermedad Crónica , Claritromicina/uso terapéutico , Femenino , Helicobacter pylori , Humanos , Masculino , Omeprazol/uso terapéutico , Recuento de Plaquetas
10.
Clin Chem Lab Med ; 50(2): 357-60, 2011 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-22022981

RESUMEN

BACKGROUND: Nucleated red blood cells (NRBCs) are present in the peripheral blood of several hematological and non-hematological conditions, usually associated with bad prognosis. The lack of an easy, rapid and reliable NRBCs count method did no't allow one to know the incidence of NRBCs and to quantify them: the count was usually done during the microscopic revision of a blood smear; this is the reason we found few studies on NRBCs automated count in the literature. The aim of this study was the evaluation of the presence and the quantification of NRBCs in some onco-hematological disorders. METHODS: This study analyzed 478 patients with the automated hematology analyzer Sysmex XE2100. The range of NRBCs were calculated in the peripheral blood at diagnosis, at hematological remission and during therapy. RESULTS: NRBCs are present in the peripheral blood of a high number of hematological diseases and are related to ineffective erythropoiesis or stress erythropoiesis or primary alterations of hematopoiesis. NRBCs were found in nearly all onco-hematological diseases at diagnosis, but not in all patients. NRBCs were frequently found during chemotherapy and absent at remission. CONCLUSIONS: To the authors' knowledge, this is the first study that gives a range for NRBCs count in the peripheral blood of these diseases.


Asunto(s)
Eritroblastos/citología , Enfermedades Hematológicas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Eritroblastos/química , Eritroblastos/patología , Femenino , Enfermedades Hematológicas/sangre , Humanos , Masculino , Persona de Mediana Edad
11.
Br J Haematol ; 150(6): 689-99, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20636440

RESUMEN

Impaired switching from fetal haemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal haemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate ß-thalassaemia and sickle cell anaemia. Fetal haemoglobin levels are regulated by complex mechanisms involving factors linked or not to the ß-globin gene (HBB) locus. To search for factors putatively involved in the expression of the γ-globin genes (HBG1, HBG2), we examined the reticulocyte transcriptome of three siblings who had different HbF levels and different degrees of ß-thalassaemia severity although they had the same ΗBA- and ΗΒB cluster genotypes. By mRNA differential display we isolated the cDNA coding for the cold shock domain protein A (CSDA), also known as dbpA, previously reported to interact in vitro with the HBG2 promoter. Expression studies performed in K562 and in primary erythroid cells showed an inverse relationship between HBG and CSDA expression levels. Functional studies performed by Chromatin Immunoprecipitation and reporter gene assays in K562 cells demonstrated that CSDA is able to bind the HBG2 promoter and suppress its expression. Therefore, our study demonstrated that CSDA is a trans-acting repressor factor of HBG expression and modulates the HPFH phenotype.


Asunto(s)
Proteínas Potenciadoras de Unión a CCAAT/fisiología , Proteínas de Choque Térmico/fisiología , Talasemia beta/genética , gamma-Globinas/biosíntesis , Adulto , Proteínas Portadoras/genética , Células Cultivadas , Femenino , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Células K562 , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Proteínas Oncogénicas v-myb/genética , Linaje , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Interferencia de ARN , Proteínas Represoras , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Transcripción Genética , Talasemia beta/metabolismo , gamma-Globinas/genética
12.
Br J Haematol ; 144(4): 552-8, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19036077

RESUMEN

We report the long-term follow-up (median 39.5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 x 10(9)/l at a median 20.2 months from treatment. Kaplan-Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders (P = 0.027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88.9% vs. 56.7%, P = 0.037). Earlier responses (within 20 d from treatment) were significantly associated with both complete (P = 0.004) and sustained response (P = 0.002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inmunosupresores/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Factores de Edad , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/efectos adversos , Lactante , Masculino , Recuento de Plaquetas , Pronóstico , Púrpura Trombocitopénica Idiopática/sangre , Recurrencia , Rituximab , Análisis de Supervivencia , Resultado del Tratamiento
13.
Clin Chem Lab Med ; 47(12): 1539-42, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19824799

RESUMEN

BACKGROUND: The technology to recognize nucleated red blood cells (NRBC) automatically has only recently been developed. Modern hematology analyzers allow for rapid and accurate NRBC counts. The goal of our study was to evaluate NRBC counts and the concentrations of serum transferrin receptor (sTfR) in patients affected by different thalassemia syndromes and hereditary spherocytosis. We wished to gain a better understanding of the meaning of the presence of NRBC in peripheral blood and the relationship of the two parameters with effective and ineffective erythropoiesis in the different thalassemia syndromes. METHODS: NRBC counts in peripheral blood were evaluated in a large group of patients with thalassemia (36 thalassemia major, 55 thalassemia intermedia and 61 Sbeta-thalassemia patients) and compared with data from 29 patients with hereditary spherocytosis; in all the patients the concentration of sTfR was evaluated as an index of global erythropoiesis. RESULTS: The NRBC count showed a good relationship with ineffective erythropoiesis: highest counts were observed in the thalassemia syndromes characterized by almost completely ineffective erythropoiesis. NRBCs were absent in patients affected by hereditary spherocitosis, a disease characterized by effective erythropoiesis. CONCLUSIONS: The NRBC count can be useful for better defining ineffective erythropoiesis in patients with thalassemia, and can help optimize transfusion therapy in severe thalassemia syndromes.


Asunto(s)
Núcleo Celular , Eritrocitos/metabolismo , Eritropoyesis , Receptores de Transferrina/sangre , Talasemia/sangre , Humanos
14.
J Allergy Clin Immunol Pract ; 7(5): 1568-1577, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30716504

RESUMEN

BACKGROUND: In the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, variable phenotypic expression may delay diagnosis. Panleukopenia, malignancy, and chronic lung disease all affect morbidity and mortality risks. Routinely used treatments include immunoglobulins, granulocyte-colony stimulating factor (G-CSF), and antibiotics; recent trials with a target C-X-C chemokine receptor type 4 (CXCR4) antagonist show promising results. OBJECTIVE: We sought to characterize the largest cohort of patients with WHIM and evaluate their diagnostic and therapeutic management. METHODS: Data were collected from an international cohort of 18 patients with CXCR4 mutations. RESULTS: The clinical features manifested at 2.2 ± 2.6 years of age, whereas the disease diagnosis was delayed until 12.5 ± 10.4 years of age. Patients with WHIM commonly presented with a severe bacterial infection (78%). Pneumonia recurrence was observed in 61% of patients and was complicated with bronchiectasis in 27%. Skin warts were observed in 61% of patients at a mean age of 11 years, whereas human papilloma virus (HPV)-related malignancies manifested in 16% of patients. All the patients had severe neutropenia (195 ± 102 cells/mm3 at onset), whereas lymphopenia and hypogammaglobulinemia were detected in 88% and 58% of patients, respectively. Approximately 50% of patients received antibiotic prophylaxis, whereas G-CSF and immunoglobulin treatments were used in 72% and 55% of patients, respectively. CONCLUSIONS: The WHIM syndrome onsets early in life and should be suspected in patients with chronic neutropenia. Patients with WHIM need careful monitoring and timely intervention for complications, mainly lung disease and HPV-related malignancies. We suggest that immunoglobulin therapy should be promptly considered to control the frequency of bacterial infections and prevent chronic lung damage.


Asunto(s)
Bronquiectasia/fisiopatología , Infecciones por Papillomavirus/fisiopatología , Neumonía/fisiopatología , Enfermedades de Inmunodeficiencia Primaria/fisiopatología , Verrugas/fisiopatología , Anomalías Múltiples , Adolescente , Adulto , Edad de Inicio , Antibacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias del Ano/etiología , Neoplasias del Ano/terapia , Neoplasias del Ano/virología , Niño , Preescolar , Enfermedad Crónica , Codón sin Sentido , Estudios de Cohortes , Criocirugía , Diagnóstico Tardío , Progresión de la Enfermedad , Femenino , Mutación del Sistema de Lectura , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Cardiopatías Congénitas , Humanos , Imiquimod/uso terapéutico , Lactante , Recién Nacido , Queratolíticos/uso terapéutico , Deformidades Congénitas de las Extremidades , Enfermedades Pulmonares/fisiopatología , Linfopenia/fisiopatología , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/inmunología , Enfermedades de Inmunodeficiencia Primaria/terapia , Receptores CXCR4/genética , Retinoides/uso terapéutico , Ácido Salicílico/uso terapéutico , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/virología , Verrugas/genética , Verrugas/inmunología , Verrugas/terapia , Adulto Joven
15.
J Chemother ; 31(1): 9-14, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30508410

RESUMEN

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016-September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.


Asunto(s)
Enfermedades Cutáneas Infecciosas , Infecciones de los Tejidos Blandos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Sistema de Registros , Adulto Joven
16.
Haematologica ; 93(12): 1859-67, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18945748

RESUMEN

BACKGROUND: Donor/recipient mixed chimerism has been reported to be associated with an increased risk of graft failure in patients with beta-thalassemia given a bone marrow transplant. We investigated the relationship between the degree of mixed chimerism over time and clinical outcome of children undergoing cord blood transplantation for beta-thalassemia. DESIGN AND METHODS: Twenty-seven consecutive children given a cord blood transplant from a related donor were analyzed by short tandem repeat polymerase chain reaction and their chimerism results were compared with those of 79 consecutive patients who received a bone marrow transplant from either a relative (RD-BMT, n=42) or an unrelated donor (UD-BMT, n=37). Cord blood and bone marrow recipients received comparable preparative regimens. RESULTS: All cord blood recipients engrafted and displayed mixed chimerism early after transplantation; 13/27 converted to full donor chimerism over time, while 14 maintained stable mixed chimerism; all patients are alive and transfusion-independent. Twenty-four of the 79 bone marrow-recipients (12 UD- and 12 RD-BMT) exhibited full donor chimerism at all time points examined, 4/79 (2 UD- and 2 RD-BMT) did not engraft and 51/79 (23 UD- and 28 RD-BMT) displayed mixed chimerism at the time of hematologic reconstitution. Forty of 51 bone marrow recipients with mixed chimerism converted to full donor chimerism (17 UD- and 23 RD-BMT), 3/51 maintained stable mixed chimerism (1 UD- and 2 RD-BMT), while 8/51 (5 UD- and 3 RD-BMT) progressively lost the graft, and became transfusion-dependent again. CONCLUSIONS: Mixed chimerism is a frequent event and does not predict the occurrence of graft failure in children with beta-thalassemia given a cord blood transplant from a relative.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Rechazo de Injerto/diagnóstico , Valor Predictivo de las Pruebas , Quimera por Trasplante , Talasemia beta/terapia , Adolescente , Niño , Preescolar , Femenino , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Humanos , Lactante , Masculino , Estudios Retrospectivos , Hermanos , Donantes de Tejidos , Trasplante Homólogo , Adulto Joven
17.
Acta Haematol ; 119(1): 1-7, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18176072

RESUMEN

BACKGROUND: Consensus guidelines for diagnosis and treatment of acute childhood idiopathic thrombocytopenic purpura (ITP) were published in 2000 by the Italian Association of Pediatric Haematology and Oncology (AIEOP). The assessment of guideline implementation was the primary objective of the present study. PATIENTS AND METHODS: Information on each newly diagnosed case of ITP referring to centres conforming with the guidelines was obtained by a questionnaire. RESULTS: Data concerning 609 new cases of acute childhood ITP were collected including 346 (56.8%) asymptomatic-paucisymptomatic forms (type A), 262 (43%) intermediate clinical forms (type B), and 1 (0.2%) severe form (type C). At diagnosis, 82% of cases were hospitalized. Age, platelet count and duration of hospitalization were significantly different in type A and type B cases. Of the total number of cases, 25% were kept under observation, 38.6% received intravenous immunoglobulins, 23.9% oral or parenteral steroids, and 12.7% other treatments. The initial treatment turned out to be appropriate for 428 cases (72.2%), of uncertain appropriateness in 71 (11.9%), and inappropriate in 95 cases (15.9%). The total level of implementation was 84.1%. CONCLUSIONS: A high rate of guideline implementation was observed during the study period. The guidelines should be reviewed taking into account more recent evidence.


Asunto(s)
Púrpura Trombocitopénica Idiopática/terapia , Enfermedad Aguda , Adolescente , Corticoesteroides/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Tiempo de Internación , Masculino , Recuento de Plaquetas , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Encuestas y Cuestionarios
18.
Exp Hematol ; 34(10): 1429-34, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16982336

RESUMEN

OBJECTIVE: Effector phase of acute graft-versus-host disease (a-GVHD) is mainly mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut-associated lymphoid tissues is ascribed to the alpha4beta7 integrin. We reasoned that development of intestinal a-GVHD might be triggered by recruitment in the intestinal mucosa of circulating, alloreactive, alpha4beta7(+) donor T cells. Therefore, we evaluated the correlation existing between circulating beta7(+) T-lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and occurrence of a-GVHD. PATIENTS AND METHODS: Surface expression of beta7 integrin on T cells was evaluated by means of direct immunofluorescence, in three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal involvement, and 38 did not develop a-GVHD. Patients were studied early after initial signs of hematologic reconstitution and before occurrence of a-GVHD. RESULTS: We found a significantly higher absolute number of CD8(+) and a significantly lower percentage of CD8(+)CD45RA(+)beta7(+) T cells in patients with intestinal a-GVHD than in patients with a-GVHD without intestinal involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a-GVHD occurred in over 70% of patients showing an absolute number of CD8(+) T cells > or = 60 x 10(6)/L and a percentage of circulating CD8(+)CD45RA(+)beta7(+) T cells < 35%. CONCLUSION: Measuring the absolute number of CD8(+) T cells and percentage of CD8(+)CD45RA(+)beta7(+) T cells at time of hematologic reconstitution may help identify patients at risk of developing intestinal a-GVHD who could benefit from strategies aimed at hampering alloreactive T-cell homing to intestinal mucosa.


Asunto(s)
Linfocitos T CD8-positivos/metabolismo , Enfermedad Injerto contra Huésped/sangre , Trasplante de Células Madre Hematopoyéticas , Cadenas beta de Integrinas/sangre , Integrinas/sangre , Enfermedades Intestinales/sangre , Enfermedad Aguda , Adolescente , Adulto , Biomarcadores/sangre , Linfocitos T CD8-positivos/patología , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Cadenas beta de Integrinas/biosíntesis , Integrinas/biosíntesis , Enfermedades Intestinales/etiología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Recuento de Linfocitos/métodos , Masculino , Neoplasias/sangre , Neoplasias/complicaciones , Neoplasias/terapia , Trasplante Homólogo
19.
Exp Hematol ; 33(4): 480-6, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15781339

RESUMEN

OBJECTIVE: Functional recovery of B lymphocytes after hematopoietic stem cell transplantation (HSCT) can take up to 2 years. HSCT recipients may obtain protective titers of pathogen-specific antibody through vaccination, but optimal timing of reimmunization remains to be defined. PATIENTS AND METHODS: In this study, we evaluated the reconstitution of B-cell number and activity in 139 children given HSCT, by B-cell subset phenotyping and in vitro immunoglobulin (Ig) production. RESULTS: Patients were longitudinally studied at 3, 6, 12, and 18 to 24 months after transplantation. At all time points, recipients displayed a significantly higher percentage of naive (IgD+CD27-) B cells and showed significantly lower production of stimulated in vitro Ig as compared to healthy controls. Moreover, during follow-up, we observed an increase in the proportion of patients who had CD27+ B subsets and who were able to mount in vitro Ig production greater than the 5th percentile. CONCLUSION: Similar to what has been described in adults, most children lack memory B cells and produce low amounts of Ig. However, the number of B cells, as well as their function, gradually recovered over time and the spread of data we observed suggests that the reimmunization schedule should be individualized for each patient. It remains to be defined in a prospective clinical study the time point at which a patient should start reimmunization. A reasonable hypothesis to be explored is the time point at which a percentage of memory B cells greater than the 5th percentile of normal controls is reached.


Asunto(s)
Linfocitos B/inmunología , Hematopoyesis/inmunología , Trasplante de Células Madre Hematopoyéticas , Memoria Inmunológica , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral , Adolescente , Adulto , Formación de Anticuerpos , Linfocitos B/fisiología , Niño , Preescolar , Femenino , Humanos , Inmunoglobulinas/biosíntesis , Lactante , Estudios Longitudinales , Masculino , Vacunación
20.
Blood Transfus ; 12(3): 340-5, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24887226

RESUMEN

BACKGROUND: The aim of this study was to investigate the effect of the combined administration of intravenous immunoglobulins and steroids as a second-line therapy in 34 children with primary immune thrombocytopenia and persistent, symptomatic bleeding. MATERIALS AND METHODS: Combined therapy (intravenous immunoglobulins 0.4 g/kg daily on days 1 and 2, and methylprednisolone 20 mg/kg daily on days 1-3) was administered to 12 patients with newly diagnosed ITP who did not respond to the administration of a single therapy (either intravenous immunoglobulins or steroids) and to 22 children with persistent and chronic disease who required frequent administrations (i.e. more frequently than every 30 days) of either immunoglobulins or steroids (at the same standard dosages) in order to control active bleeding. RESULTS: A response (i.e. platelet count >50×10(9)/L and remission of active bleeding) was observed in 8/12 (67%) patients with newly diagnosed ITP. The clinical presentation of responders and non-responders did not differ apparently. Patients in the chronic/persistent phase of disease had a significantly longer median period of remission from symptoms compared with the previous longest period of remission (p=0.016). The treatment was well tolerated. DISCUSSION: Our data suggest that the combined approach described is a well-tolerated therapeutic option for children with primary immune thrombocytopenia and persistent bleeding symptoms that can be used in both emergency and/or maintenance settings.


Asunto(s)
Glucocorticoides/administración & dosificación , Hemorragia/tratamiento farmacológico , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Metilprednisolona/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Niño , Preescolar , Enfermedad Crónica , Quimioterapia Combinada , Femenino , Glucocorticoides/efectos adversos , Hemorragia/etiología , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Factores Inmunológicos/efectos adversos , Lactante , Masculino , Metilprednisolona/efectos adversos , Púrpura Trombocitopénica Idiopática/complicaciones
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