Papers by Roberto Castelli
Journal of Thrombosis and Thrombolysis, 2020
The International Journal of Artificial Organs, 1997
C1 inhibitor (C1-INH) regulates, complement, contact system, coagulation and fibrinolysis. Bleedi... more C1 inhibitor (C1-INH) regulates, complement, contact system, coagulation and fibrinolysis. Bleeding complications during cardiopulmonary bypass (CPB) have been described in a deficient patient. We report a 72 year old man affected with acquired C1-INH deficiency who successfully underwent CPB.
Journal of Clinical Medicine
Background: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Gu... more Background: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Guidelines suggest iron supplementation for unresponsive patients, regardless of iron deficiency. The primary aim of this study was to evaluate the effect of iron supplementation with ferric carboxymaltose (FCM) on the reduction of red blood cell transfusion (RBCT) rate in transfusion-dependent RA patients. Methods: This was a prospective quasi-randomized study, wherein patients were randomly assigned into three groups: (A) ESAs alone, (B) ferric gluconate (FG) and ESAs, and (C) FCM and ESAs. Hemoglobin and ferritin levels, as well as the number of RBCTs at 4 and 28 weeks were compared. Economic evaluation was also performed. Results: A total of 113 RA patients were enrolled. In total, 43 were treated with intravenous FG and ESAs, 38 with FCM and ESAs, and 32 with ESAs alone. At both follow-ups, erythropoietic response was increased in those receiving iron as compared with those with ESAs ...
Journal of Allergy and Clinical Immunology, 2016
European Journal of Internal Medicine, 2008
To evaluate diagnostic value of autonomic tests in relation with age, to evaluate predictors of n... more To evaluate diagnostic value of autonomic tests in relation with age, to evaluate predictors of neuromediated syncope and the presence of complex diagnosis in patients with syncope unexplained after initial evaluation. Methods: Indication to neuroautonomic evaluation were: 1. first line evaluation-history, physical examination and ECG-suggestive of neurally-mediated syncope; 2. first line evaluation suggestive of cardiac syncope excluded after specific diagnostic tests; 3. none certain or suspected diagnostic criteria after the first line evaluation. All patients were evaluated with neuroautonomic tests: Tilt Table Test (TTT) potentiated with sublingual nitro-glycerine, Carotid Sinus Massage (CSM) in supine and upright position and Orthostatic Hypotension (OH). Results: We enrolled 873 consecutive patients (373 men and 500 18 years). 584 (mean age 77,2±7 years) were aged 65 and?women, mean age 66,5 older. Neuroautonomic evaluation was diagnostic in 64,3% of the cases (64,7% in younger vs 64,2% in older, p=ns). TTT was diagnostic in 50,4% of the cases, CSM was diagnostic in 11,8% and OH was present in 19,9% of the cases. Vasovagal syncope had a similar distribution in any decades of age. Predictors of a positive response to TTT were the presence of prodromic symptoms and a typical situational syncope. The presence of a positive response to CSM increased with age; age and abnormal ECG were predictors of a positive response to CSM. Venous incontinence and alpha blockers, nitrates and benzodiazepines therapy resulted associated with the presence of OH. 129 (23%) patients presented a complex diagnosis. The most frequent association resulted the coexistence of vasovagal syncope and OH (15,8% of the cases). Complex diagnosis was present in 42,9% in patients aged 80 and older; age was the strongest predictor of complex diagnosis. Conclusions: neuroautonomic diagnostic tests are very useful in patients with unexplained syncope after initial evaluation, both in young and older. Complex neuromediated diagnosis is very frequent in older patients
Anti-Cancer Drugs
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) has been considered th... more R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) has been considered the standard of care for diffuse large B cell lymphoma (DLBCL) patients, including in the elderlies, and represent the current standard treatment. Ineligibility for R-CHOP-like treatments seems to be associated with shorter survival. Recent studies have shown that bendamustine and rituximab is linked, in elderly patients affected by DLBCL. Here we report our experience with BR in 40 elderly frail patients affected by DLBCL ineligibles for R-CHOP. The OOR was 77.5%, with 22 complete responses and 9 partial responses statistical analysis showed no significant difference in overall survival (OS) between patients aged 80 years and older and patients younger than 80 years (6·4 vs. 10·2 months, respectively, P = 0·43). Complete responders were more likely patients with good performance status, (ECOG 0-1) 13 patients (60%), 9 patients (40%) were ECOG 2; of the 9 patients who achieved partial response, 7 patients had ECOG 0-1 and 2 patients had ECOG 2. Four patients had stable disease. Progression-free survival (PFS) median PFS was 13.5 months. These preliminary results showed that bendamustine and rituximab has been associated with high response rates, acceptable toxicity in frail DLBCL patients and high rate of OSS. In older patients with advanced IPI scores, no significant difference in OS were observed between patients aged 80 years and older and patients younger than 80 years. We conclude that bendamustine and rituximab seems to be a reasonable alternative for frail DLBCL patients.
Frontiers in Cardiovascular Medicine
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapp... more Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping myelodysplastic and myeloproliferative features. The disease is generally characterized by blood monocytosis, bone marrow dysplasia, cytopenia, and hepatosplenomegaly. While malignant blood diseases are frequently associated with a high risk of thromboembolism, CMML is often accompanied by immune-mediated hemorrhagic diathesis. Indeed, very few reports in literature report thrombotic complications of CMML patients. We will briefly present here the case of a patient with CMML who developed a massive right atrial thrombus. We aim to highlight the non-negligible thrombotic burden of the disease, and we will get through the differential diagnosis of right atrial masses and the management of right atrial thrombi, which are a rare and poorly known entity.
Cancer Medicine
The ZBTB16-RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromo... more The ZBTB16-RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor-α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to alltrans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis. Aims: The mutational profile of ZBTB16-RARA rearranged AML has not been described so far. Materials and methods: We performed targeted next-generation sequencing of 24 myeloid genes in BM diagnostic samples from seven ZBTB16-RARA+AML, 103 non-RARA rearranged AML, and 46 APL. The seven ZBTB16-RARA-positive patients ORCID
Hematology and Blood Disorders
Pathology - Research and Practice, 2014
In a small subset of polycytemia vera (PV), neutrophilia not secondary to reactive conditions or ... more In a small subset of polycytemia vera (PV), neutrophilia not secondary to reactive conditions or treatment can develop and persist. Clinical significance and morphogenetic alterations associated with this uncommon phenomenon are not well defined. An 81-year-old Caucasian woman, affected by polycytemia vera lasting 17 years, presented in March 2012 with hyperleukocytosis, absolute neutrophilia, and thrombocytosis despite hydroxyurea treatment. All other laboratory parameters were normal, except for an increased neutrophil alkaline phosphatase and lactate dehydrogenase. Reactive neutrophilia due to infection or neoplasia have been ruled out by a total body computerized tomography scan, and by low levels of C reactive protein. Re-evaluation of bone marrow showed hypercellular smears with expansion of granulopoiesis while immature granulocytes were <10% and myeloblasts were <1%. Bone marrow trephine biopsy showed hypercellular marrow, with panmyelosis, increased myeloid/erithroid ratio, polymorphic clusters of megakaryocytes. A loose network of reticulin fibers with many intersections was identified by means of Gomori's silver impregnation. There were no hybrid BCR/ABL gene transcripts of p210, p190 and p230, no mutations in platelet derived growth factor receptors alpha and beta. Flow cytometry on the aspirate showed that CD34+ CD117+ myeloblasts constituted less than 1% of total marrow nucleated cells, mature granulocytes demonstrated persistent expression of CD33. Mutational analysis of the gene CSF3R by PCR amplification revealed no alterations in exons 14-17, including codons 615 and 618. The case presented here represents a possible evolution of PV, albeit very rare. The condition described here differs from the CNL for the persistence of morphological pictures typical of myeloproliferative diseases, for absence of CSF3R gene mutations and for the hyper expansion of the mature granulopoietic series. The clinical significance and morphogenetic alterations associated with this uncommon phenomenon are not well defined.
Vascular Medicine, 2004
The association between cancer and thromboembolic disease is a well-known phenomenon and can cont... more The association between cancer and thromboembolic disease is a well-known phenomenon and can contribute significantly to the morbidity and mortality of cancer patients. The spectrum of thromboembolic manifestations in cancer patients includes deep vein thrombosis, pulmonary embolism, but also intravascular disseminated coagulation and abnormalities in the clotting system in the absence of clinical manifestations. Unfractioned heparin (UFH) and particularly low molecular weight heparins (LMWHs) are widely used for the prevention and treatment of thromboembolic manifestations that commonly accompany malignancies. Malignant growth has also been linked to the activity of heparin-like glycosoaminoglycans, to neoangiogenesis, to protease activity, to immune function and gene expression. All these factors contribute in the proliferation and dissemination of malignancies. Heparins may play a role in tumour cell growth and in cancer dissemination. The aims of the study are to review the effi...
Clinical and Applied Thrombosis/Hemostasis, 2007
The influence of age on predisposing factors, diagnostic tests, and clinical presentation of pulm... more The influence of age on predisposing factors, diagnostic tests, and clinical presentation of pulmonary embolism was evaluated in 582 subjects with suspected pulmonary embolism (180 aged <65 years; 402 aged ≥65 years) consecutively enrolled at the Emergency Department. Pulmonary embolism was confirmed in 40% of patients, 75% of those were aged >65 years. Age was directly related to the diagnosis, and the observed probability was higher than the expected probability in the 70 to 79 year subgroup. Score at the Cumulative Illness Rating Scale significantly increased as a function of both age and pulmonary embolism. Dyspnea, syncope, jugular distension, and history of previous venous thromboembolism were more frequently observed in elderly patients. In-hospital mortality rate among the elderly and younger patients was 2% and 0.2%, respectively. The authors conclude that age ≥65 years and high comorbidity are risk factors for pulmonary embolism.
Blood Coagulation & Fibrinolysis, 2011
Thrombin, the central bioregulatory enzyme of haemostasis, also has a potent vasopermeability eff... more Thrombin, the central bioregulatory enzyme of haemostasis, also has a potent vasopermeability effect on the surface of endothelial cells, and has therefore been considered a major link between the activation of the coagulation pathway and inflammation. C1 inhibitor inhibits thrombin with a low second-order rate constant that can be increased by heparin. The aim of this study was to investigate whether the C1 inhibitor-induced inhibition of thrombin is potentiated on the endothelial surface. The interaction of C1 inhibitor and thrombin was evaluated in an in-vitro system of human umbilical vein endothelial cells (HUVECs) to which purified C1 inhibitor and thrombin have been added. The role of heparins and selectins has been tested by adding heparinase and Mab to selectins. Kinetic analysis under pseudo-first-order conditions showed that the inhibitory effect of C1 inhibitor on thrombin is greater on the surface of endothelial cells. After incubating nanomolar concentrations of thrombin and micromolar concentrations of C1 inhibitor in a purified system, thrombin activity remained significant, but was almost totally suppressed in the presence of HUVECs. The abolition of such suppression by heparinase and Mab to selectins supports the involvement of heparin and selectins in C1 inhibitor-thrombin interaction. Furthermore, the second-order rate constant was 25 ± 3 /s per mol/l in our purified system, but increased to 100 ± 9 /s per mol/l in the presence of HUVECs. Our results indicate that C1 inhibitor can inhibit thrombin activity on vascular endothelium via binding to selectins and potentiation by heparins. This may contribute to the modulation of thrombin activity on vasopermeability and on coagulation especially when the major natural anticoagulant pathways are impaired.
American Journal of Hematology, 2006
Cardiovascular Involvement in Adult Granulocytic Sarcoma To the Editor: Granulocytic sarcoma, a l... more Cardiovascular Involvement in Adult Granulocytic Sarcoma To the Editor: Granulocytic sarcoma, a localized tumor mass composed of immature cells derived from the hematopoietic myeloid series, could infiltrate any extramedullary site; however, mediastinal involvement is distinctly rare [1].
Vascular Medicine, 2003
Syncope as an initial presentation of pulmonary embolism occurs in 10% of patients. We compared c... more Syncope as an initial presentation of pulmonary embolism occurs in 10% of patients. We compared clinical and instrumental parameters in patients with syncope as the presenting symptom of pulmonary embolism and in patients with documented pulmonary embolism without syncope. Seventy patients with the diagnosis of pulmonary embolism and apparently stable clinical conditions were evaluated. They were divided in two groups: 10 patients with syncope as the presenting symptom of pulmonary embolism (group 1) and 60 patients without syncope (group 2). Patients with syncope showed a more pronounced tendency to present with main pulmonary artery embolus than patients without syncope (contingency coefficient = 0.301, p < 0.04; one-tailed). However, despite the evidence that patients with syncope have significant reductions in systolic and=or diastolic blood pressure, shock was not observed in any patient. In no case was thrombolytic treatment given and all patients received standard anticoag...
Blood
1596 Angioedema with acquired deficiency of C1 inhibitor (C1-INH) is a rare syndrome associated w... more 1596 Angioedema with acquired deficiency of C1 inhibitor (C1-INH) is a rare syndrome associated with B lymphocyte disorders, usually identified as acquired angioedema (AAE). The clinical features of C1-INH deficiency, more often of genetic origin (hereditary angioedema HAE), include subcutaneous swelling, edema of the gastrointestinal wall causing temporary bowel obstruction with severe pain and edema of the upper respiratory tract that can lead to asphyxia. AAE associated B cell disorders result in autoantibodies to C1-INH, monoclonal gammopathies of uncertain significance (MGUS) and non Hodgkin Lymphomas (NHL). The 3 conditions may be concomitantly present suggesting that expansion of an anti C1-INH B lymphocyte clone is the primum movens of the disease. The burden of AAE derives from either the associated limphoproliferative disorder or the frequency and severity of angioedema symptoms: both conditions may lead to death. Here we report on the long term follow up of 48 patients (m...
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Papers by Roberto Castelli