Search

Background: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings., Aim: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital., Methods: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods., Findings: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response., Conclusion: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We determined the prevalence of incidental extracardiac findings (IEF) at Magnetic Resonance Imaging (MRI) potentially related to anemia and hypoxia in age- and sex-matched populations (N = 318) with thalassemia major (TM) and thalassemia intermedia (TI) enrolled in the Myocardial Iron Overload in Thalassemia network. Overall, IEFs were detected in 33.3% and 25.8% of patients with TI and TM, respectively (P = 0.114). TI and TM patients had elevated but comparable prevalence of renal, splenic and liver cysts, and vertebral hemangiomas while TI patients had a significant higher frequency of extramedullary hematopoiesis (EMH) (15.1% vs 4.4%; P = 0.002). The prevalence of total IEFs increased with advancing age. TI non-transfusion-dependent patients had a significantly lower frequency of renal cysts than TI transfusion-dependent patients (8.8% vs 26.4%; P = 0.005). The prevalence of renal cysts in the thalassemic population was significantly higher than that in the general population (19.2% vs 1.9%; P < 0.0001). Our data on renal cysts indicate a significant higher prevalence of these IEFs compared to the general population, suggesting the role of the inappropriate activation of the hypoxia-inducible factor system linked to the chronic hypoxia. The significant prevalence of IEF in thalassemia patients undergoing MRI for iron quantification should prompt the discussion of the inclusion of IEF in the MRI report.

Heart disease remains a leading cause of morbidity and mortality in transfusion-dependent thalassemia (TDT), which can be attributed to several factors but primarily develops in the setting of iron overload. This was a retrospective cohort study utilizing Webthal ® patient data from five major centers across Italy. Patients without heart disease were followed-up for 10 years (2000-2010) and data were collected for demographics, splenectomy status, serum ferritin and hemoglobin levels, and comorbidities associated with heart disease. Among 379 patients analyzed (mean age 22.9 ± 5.1 years, 47.8% men), 44 (cumulative incidence: 11.6%) developed heart disease during the period of observation. Splenectomy (p = 0.002) and serum ferritin level (p < 0.001) were the only risk factors with significant association with heart disease. A serum ferritin threshold of ≥ 3000 ng/mL was the best predictor for the development of heart disease (86.4% sensitivity and 92.8% specificity, AUC: 0.912, 95% CI 0.852-0.971, p < 0.001). On multivariate analysis, only a serum ferritin level ≥ 3000 ng/mL remained significantly and independently associated with increased risk of heart disease (HR: 44.85, 95% CI 18.85-106.74), with a 5- and 10-year heart disease-free survival of 58 and 39%. The association between iron overload and heart disease in patients with TDT is confirmed, yet a new serum ferritin level of 3000 ng/mL to flag increased risk is suggested.

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., (© 2014 John Wiley & Sons Ltd.)

This paper aims to shed light on Italian contribution to the origins of malaria hypothesis, also known as Haldane hypothesis. The first studies on the association between hemoglobinopathies and malaria, in fact, were done in Italy since the end of the 1920s. These studies tried to explain the correlation between malaria and thalassemia observed by clinicians in various Italian regions. Later, since the beginning of the 1940s, this singular correlation was documented by thorough and wide-ranging epidemiological researches that revealed a strong geographic correspondence between the frequency of the thalassemic features and endemic malaria in Italy. These researches raised clearly the question of maintaining the frequency of a gene that, at the time, doomed homozygotes to death within the first two years of life. In 1948, Silvestroni, Bianco and Montalenti started investigating the causes of the persistence of the thalassemic foci in Italy. In 1949 J.B.S. Haldane finally hypothised for the first time an evolutionary advantage of thalassemic condition due to the concomitant presence of malarial infection. Since 1948, Montalenti and Haldane had various occasions to discuss on this topic. I try to demonstrate the role of Silvestroni, Bianco and Montalenti's research and data on the formation of Haldane hyphothesis.

High frequencies of both thalassemia trait (5.2%) and glucose 6-phosphate dehydrogenase (G6PD) deficiency for only males (1.3%) have been observed in the Calabrian population. The G6PD activity measurement was carried out on 1239 samples of whole blood from Calabrian subjects of both sexes (age range 10-55) by a differential pH-metry technique which was quite suitable to determine the G6PD deficiency in mass screenings. The analyzed subjects showed: only the thalassemia trait; or only the G6PD deficiency; or only the total iron serum deficiency; or G6PD deficiency associated with the thalassemia trait or with the total iron serum deficiency. The G6PD heterozygous subjects have an enzymatic activity which is masked by both the thalassemia trait and the total iron serum deficiency. In a population showing high frequencies of both thalassemia trait and G6PD deficiency, the comparison of G6PD activity of heterozygous subjects also affected with the thalassemia trait is more reliable if referred to the enzymatic activity of the carriers of the latter inherited anomaly rather than to G6PD activity of normal subjects.

With the improved life expectation of patients with beta-thalassemia-major (BTM) or Cooley's Disease, new clinical problems, such as hearing damage, have emerged. The authors describe audiometric data of 50 patients with BTM. High-frequency thresholds were higher in BTM than those of a control group. Prevalence of hearing loss in BTM was 14-26%, depending on the frequency range considered, while in the control group it was between 4.3-19.1%. The prevalence of hearing loss in BTM with respect to that of the general population was 7-10% higher. Hearing loss ranged from mild to moderate. A good correlation was found between hearing loss and the cumulative dose of desferoxamine administered. These data were indicative of an ototoxic effect of this drug. Many patients (28.6%) showed significant hearing threshold deterioration after 3 years. On the light of these results, the authors suggest regular audiologic follow-up of patients with BTM.

A total of 4401 subjects admitted to the Medical Division of St Camillo Hospital in Comacchio (Ferrara, Italy) over a period of 7 years were prospectively evaluated in order to determine whether the heterozygous beta-thalassaemic (HBT) could be considered as a protective factor against the occurrence of acute myocardial infarction (AMI). Of the total patient sample, 3954 subjects were non beta-thalasaemics (NBTs), and 447 subjects were heterozygous beta-thalassaemics (HBTs). AMI was diagnosed in 384 patients, of whom 17 individuals were HBTs and 367 subjects were NBTs. The prevalence of HBTs in this group was significantly lower than expected (4.43%, P less than 0.0001). Furthermore, an analysis by sex showed that this lower prevalence could be attributed to male patients. Moreover, only in male subjects was a significant negative correlation observed between AMI and HBT. The mean age at which AMI occurred in male HBTs was significantly higher than in male NBTs (72 +/- 2.69 vs. 63 +/- 0.7 years, P less than 0.05), while no differences were found in the mean age at which AMI occurred between HBT and NBT female subjects. This study demonstrates that the thalassaemic trait may afford some protection against the occurrence of AMI in men.

This paper describes the status of iron stores, the incidence and the hematological characteristics of iron deficiency anemia in children heterozygous for beta-thalassemia. In beta-thalassemia heterozygotes, iron stores were similar to the controls in infancy and tended to increase with age, reaching levels of moderate iron overload solely in adult males. Iron deficiency anemia occurred less frequently in children heterozygous for beta-thalassemia as compared to normal controls, while no difference between the two groups was observed in the incidence of iron deficiency. Ineffective erythropoiesis, typical of heterozygous beta-thalassemia, by causing an increase of iron absorption may limit the effect of iron shortage. At similar levels of iron depletion, however, children heterozygous for beta-thalassemia develop a more severe anemia as compared to non beta-thalassemic children. With the exception of two children, HbA2 levels in the presence of iron deficiency anemia remain in the range of heterozygous beta-thalassemia. In conclusion, our results indicate that children heterozygous for beta-thalassemia have normal iron stores but are relatively protected against the development of iron deficiency. When iron deficiency anemia develops, its clinical expression is usually more severe than in non beta-thalassemic children.

47 patients with thalassemia major treated with blood transfusions were studied by the authors. The aim was to carry out an investigation on caries incidence. From the data collected in this investigation it was found that 90% of males and 66% of females showed caries, then there was a difference in percentage of caries between males and females. On the other hand the dmf and the DMF index showed quite the same values in males and in females.

The Authors report a rare case of Legionnaires' disease imported from Spain in a patient with beta-thalassaemia minor. This condition as predisposing factor for Legionella pneumophila infection is discussed, with particular emphasis on the therapeutic implications.

A family has been observed in which a beta thalassemia determinant is inherited over three generations together with high Hb F level (8-12%) and increased number of fetal-hemoglobin-containing-cells (F-cells). The values of red cell indices and globin chain synthesis ratios, yet typical of beta thalassemia, were significantly shifted to the normal values when compared with those of typical beta thalassemia heterozygotes belonging to the same family group. The occurrence in these individuals of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant and its linkage relationship with the beta thalassemia is discussed. In the third generation two adult individuals were beta thalassemia homozygotes having inherited a beta thalassemia determinant from one parent and a beta thalassemia together with the HPFH determinant from the other. They showed an extremely mild clinical condition, and 11-12 g/dl of mainly Hb F without having ever required blood transfusions. Virtually all the red cells were F-cells in both subjects. The importance of the coexistence of HPFH determinants capable of increasing the size of the F-cell population in patients affected by homozygous thalassemia is discussed, considering the sensible benefit which derives from enhanced Hb F production in this syndrome.

185 asymptomatic heroin addicts in whom the incidence of positivity as for HBsAg was 9.1%, were examined. From the anamnesis, these carriers has a higher frequency of icteric events in comparison with patient controls, while they did not show differences in distribution according to age, duration of the toxicomania and regional origin of the family. 38 heroin addicts were alcoholics too: 6/38 were HBs carriers, whereas 11/147 non alcoholic were carriers. The group of HBsAg positive addicts showed an analogous alteration of the transaminase levels as regards the patient controls, while the incidence of hypoalbuminemia and hypergammaglobulinemia was higher. In consideration of these results, the possible responsibility of toxic factors (alcohol) and alterations of the immune reactivity as to the prolonged permanence of HBsAg in circle is discussed.

Forty-four months analysis of cardiovascular diseases in a population with a high incidence of beta thalassemia trait is reported. A lower incidence of acute myocardiac infarctions, strokes, and their recurrence was observed in subjects with thalassemic trait; however they present more infarctions in later middle age and a lower incidence of atherogenic risk factors, specially hyperlipoproteinemias.

The prevalence of anti-LAV/HTLV III antibodies in serum samples of individuals at high risk for AIDS and of healthy individuals living in the province of Catania is reported. Serum samples were collected over the period 1983-86 from 220 drug addicts adults, 339 from multitransfused thalassemia patients, 71 from hemophiliacs, 22 from subjects of the hospital staff who had had contacts with positive subjects, 9 from family contacts of positive multitransfused thalassemics and 7270 from blood donors. Prevalence of antibodies among drug addicts was 14% and a positive subject was found as early as 1983. This result suggested that LAV/HTLV III was already present in Catania at that year. Among the thalassemics and the hemophiliacs the prevalence was 2.3% and 21% respectively. No positive subject was found among hospital staff nor among family contacts of positive thalassemic subjects. Three positive cases have been found among the blood donors and even though these are drug addicts, it is important to underline the necessity of a regular screening of the blood units to prevent LAV/HTLV III diffusion.

After reviewing the most recent genetic, biochemic, pathogenetic and laboratory aspects of thalassemia, the Authors refer to a statistical survey of the population of Alghero regarding the thalassemia heterozygote. In order to arrive at the "microcytosis" condition, a study of the average corpuscle volume is recommended as a screening standard. For this purpose, and for technical and economical reasons, automatic continuous flows apparatus are most suitable such as the Technicon SMA 7/A. After emphasizing the difficulty that the laboratory often encounters in diagnosing a heterozygote condition, the Authors report a thalassemic taint of 7.18% in Alghero, with a prevalence of the beta-thalassemia so called 1st type. They refer to the not rare occurrence of anaemia, in association with sideropenia and thalassemia and confirms the possible disappearance of the erythrocytary thalassemia characteristics when, together with the thalassemia there is a deficiency of G-6-PDH. The study carried out by the Authors does not reveal any proven case of alpha-thalassemia, thus confirming what other research workers have established on the rarity of this thalassemia variant in our zone, but not excluding that this apparent rarity could be attributed to an inadequacy in the present means of research.

Seven cases with the syndrome of thalassemia minor and pauciarticular, non-erosive, seronegative arthritis are described. Other known causes of seronegative arthritis had been excluded. There was a predilection for middlesized joints such as ankles, wrists and elbows. Usually the synovitis was asymmetrical from onset, with one to eight joints affected. Finger or toe joint were usually spared. Extraarticular synovitis such as tenosynovitis or bursitis were not observed, nor were nodules, signs of vasculitis or visceral involvement. The course of this arthritis showed chronicity and mild, persistent, non-erosive synovitis without joint effusions. X-ray revealed juxtaarticular osteoporosis of the affected joints, characterized by a diminution of the number of trabeculae (hypertrophic atrophy) combined with broadening of the singular trabeculae; this picture is typical of hemoglobinopathies. - Computed tomography showed a probable slight deficit of bone mineralization. Laboratory investigations including ESR, routine immunological tests, blood chemistry, and HLA-tissue typing were all normal. - The combination of this peculiar arthropathy with thalassemia minor would appear to be worthy of note and requires a further search among the forms of arthritis of unknown origin.

Among 5 families with SBH of Neapolitan origin, herediatry glyco-lipidosis was accompanied in one by beta-thalassemia. All 10 members of this family, namely parents and 8 siblings, were investigated. The mother and two children were found to be carriers of both SBH and beta-thalassemia, while three other siblings were carriers of SBH alone. None of the six patients conformed the classic clinical picture often observed in genotypical SBH. The present state of genotypic transmission of the stigma is discussed on the basis of the author's experience as well as the data in the literature. As for the combination SBH-thalassemia in the same individual it may be concluded that the two genes are most likely independent and certainly not linked.

The pilot study was designed to vindicate planning for large-scale detection and management of two parallel genetic blood disorders occurring in large numbers of Mediterranean- and black Americans; the heterozygous minor traits of thalassemia (Cooley's anemia) and sicklemia (sickle-cell anemia). Referred pupils (N=191) matched on schools, age, and learning difficulties associated with learning disabilities were compared as to presumed ethnic origin (n Mediterranean = 80; n black = 64; n "others" = 47) and incidence of trait-related learning and behavioral characteristics. Group mean differences on the study's criteria were found to be significant. Both minor-trait prone groups equally indicated the associative effects, while the control group without tradt-predisposition showed a nonsignificant relationship, thus supporting the hypotheses and the need for large-scale research.

Survival and causes of death were studied in 1087 Italian patients with thalassaemia major who were born on or after Jan 1, 1960. At the age of 15 years, the Kaplan-Meier estimate of survival after the first decade of life was 80.6% for subjects born in 1960-64, 84.2% for those born in 1965-69, and 96.9% for those born in 1970-74. At the age of 20 years, survival from the age of 10 was 59.1% for patients born in 1960-64, and 70.2% for those born in 1965-69; at 25 years, survival from the age of 10 was 40.7% in the 1960-64 cohort. Overall survival from birth for patients born in 1970-74 was 97.4% at 10 years, and 94.4% at 15 years. The most common cause of death was heart disease, followed by infection, liver disease, and malignancy.