Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practice-guidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy.     

Begelomab for severe refractory dermatomyositis: A case report

Rationale:Severe refractory idiopathic inflammatory myopathy (IIM) represents a challenge for the clinician. The lack of efficacy of available tools reflects our incomplete insight into the molecular events sustaining the inflammatory tissue damage in these patients. We present the first case of refractory IIM treated with anti-dipeptidyl peptidase-4 (DPP-4)/cluster of differentiation 26 (CD26) monoclonal antibody.Patient concerns:A 55-year old man presented with proximal muscle weakness, diffuse erythematous skin lesions which rapidly evolved into ulcerations, dysphagia and dysphonia.Diagnosis:Increased serum creatine kinase levels and histological findings at muscle and skin biopsies were compatible with the diagnosis of dermatomyositis (DM). Several lines of treatment failed to control the disease including steroids, mycophenolate mofetil, tacrolimus, intravenous immunoglobulins and rituximab. Despite therapy, the patient also had recurrent intestinal vasculitis causing bowel perforation. Concurrently, DPP-4/CD26 expression in the patient''s skin and skeletal muscle was observed.Interventions:The patient was treated with begelomab, a murine immunoglobulin G2b monoclonal antibody against DPP-4/CD26.Outcomes:Dysphagia, skin lesions and intestinal vasculitis resolved and the patient experienced a significant improvement of his quality of life.Conclusion:Blockade of DPP-4/CD26, which is expressed on T cells and mediates T cell activation and function, is safe and might be effective in patients with refractory DM.     

Human herpesvirus type 8-associated primary lymphomatous effusion in an elderly HIV-negative patient: clinical and molecular characterization

Primary lymphomatous effusions are defined as lymphomas presenting in the serous body cavities in the absence of clinically identifiable tumor masses. Recently, a peculiar type of primary lymphomatous effusion associated with tumor clone infection by human herpesvirus type 8 (HHV-8) and preferentially arising in HIV-positive patients has been described and termed as primary effusion lymphoma (PEL). This report describes a case of PEL which has developed in a HIV-negative, 92-year-old man with longstanding Mediterranean Kaposi's sarcoma, a disease also associated with HHV-8 infection. The patient presented with pleural and ascitic effusions in the absence of solid masses within the lungs, mediastinum, thoracic wall or abdominal cavity. The effusions consisted of malignant lymphocytes with morphologic features bridging immunoblastic and anaplastic cells. Immunophenotypic studies revealed that the lymphoma population expressed an antigenic profile consistent with PEL, i.e. the absence of common B- and T-cell markers (non-B, non-T phenotype) coupled to CD138 positivity. Molecular analysis demonstrated infection of the tumor clone by HHV-8 as well as monoclonally rearranged immunoglobulin genes, consistent with a B-cell histogenesis of the lymphoma. In addition, this PEL case harbored PAX-5 gene mutations, which have been recently demonstrated as a key feature of the proto-oncogene hypermutation process involved in the pathogenesis of some lymphoma types. Following two courses of etoposide and prednisone, a partial remission was achieved. The patient died of liver failure 3 months after the diagnosis of PEL. Overall, this case report illustrates the need for an integrated diagnostic approach based on clinical features, morphology, immunophenotype, and molecular genetics to primary lymphomatous effusions.     

The changing epidemiology of malaria in Ifakara Town, southern Tanzania

Between 1995 and 2000 there were marked changes in the epidemiology of malaria in Ifakara, southern Tanzania. We documented these changes using parasitological and clinical data from a series of community- and hospital-based studies involving children up to the age of 5 years. There was a right shift and lowering in the age-specific parasite prevalence in the community-based cohort studies. The incidence of clinical malaria in placebo-receiving infants in additional study cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P<0.0001). At the same time, there was an increase in the total number of malaria admissions and a marked right shift in the age pattern of these admissions (median age in 1995 1.55 years vs. 2.33 in 2000, P<0.0001). However, the burden of malaria deaths remained in infants. We discuss how these dramatic changes in the epidemiology of malaria may have arisen from the use of currently available malaria control tools. Caution is required in the interpretation of hospital-based data as it is likely to underestimate the impact of anaemia on mortality in the community, where most paediatric deaths occur. Even in low/moderate malaria transmission settings, where older children suffer most malaria episodes, targeting effective malaria control at infants may produce important reductions in infant mortality caused by malaria.     

Clinical and haematological improvement induced by etidronate in a patient with idiopathic myelofibrosis and osteosclerosis

Summary We report a patient with agnogenic myeloid metaplasia associated with debilitating bone pain due to increased bone turnover and osteosclerosis. Treatment with etidronate at a dose of 6 mg/kg per day on alternate months resulted in a complete recovery of bone symptoms and normalization of metabolic parameters of bone turnover; unexpectedly, a sustained haematological improvement was also observed after several months of therapy, suggesting that bone marrow microenvironment improvement was able to restore a nearly normal haemopoiesis. We suggest that diphosphonate therapy may be of value in patients with AMM and increased bone turnover.     

Lymphocyte and immature dendritic cell infiltrates in differentiated, poorly differentiated, and undifferentiated thyroid carcinoma.

OBJECTIVE: Numerous studies indicate that papillary thyroid carcinomas (PTC) with lymphocytic infiltrates are associated with a less extensive disease at diagnosis and improved disease-free survival. The infiltration of lymphocytes and immature CD1a+ dendritic cells (DC) was characterized in papillary, poorly differentiated (PDC), and undifferentiated (UC) carcinomas to evaluate their association with immunological infiltrates. DESIGN: A series of 527 consecutive cases of thyroid carcinoma treated by total thyroidectomy were investigated by histopathological and immunohistochemical methods. The inflammatory infiltrate was quantified and typed in intratumoral and peritumoral tissues as well as in the controlateral lobe. MAIN OUTCOME: The intratumoral infiltrate was strongly reduced or absent in PDC and UC. Intense infiltrates were detected in the PTC tall cell variant. In all histotypes, the extent of the intratumoral and peritumoral infiltrates was comparable. Immature DC were detected in PTCs and markedly reduced in PDC and UC. CD1a+ DCs were detected in a small percentage of PDC and UC. CONCLUSIONS: Though a relationship between the extent of lymphocyte/DC infiltrates and the prognosis of PTCs could not be demonstrated, tumors with poor prognosis (PDCs, UCs) were characterized by markedly reduced lymphocyte/DC infiltrates. The study appears to confirm the protective role of DC and infiltrating lymphocytes against thyroid tumors.     

Face recognition in schizophrenia: do individual and average ROCs tell the same story?

Introduction. Many studies have shown that recollection process is impaired in patients with schizophrenia, whereas familiarity is generally spared. However, in these studies, the Receiver Operating Characteristic (ROC) presented is average ROC likely to mask individual differences.

Methods. In the present study using a face-recognition task, we computed the individual ROC of patients with schizophrenia and control participants. Each group was divided into two subgroups on the basis of the type of recognition processes implemented: recognition based on familiarity only and recognition based on familiarity and recollection.

Results. The recognition performance of the schizophrenia patients was below that of the control participants only when recognition was based solely on familiarity. For the familiarity-alone patients, the score obtained on the Scale for the Assessment of Positive Symptoms (SAPS) was correlated with the variance of the old-face familiarity. For the familiarity-recollection patients, the score obtained on the Scale for the Assessment of Negative Symptoms (SANS) was correlated with the decision criterion and with the old-face recollection probability.

Conclusions. These results show that one cannot ascribe the impaired recognition observed in patients with schizophrenia to a recollection deficit alone. These results show that individual ROC can be used to distinguish between subtypes of schizophrenia and could serve as a basis for setting up specific cognitive remediation therapy for individuals with schizophrenia.