Decrease in α-Globin and Increase in the Autophagy-Activating Kinase ULK1 mRNA in Erythroid Precursors from β-Thalassemia Patients Treated with Sirolimus.

The β-thalassemias are hereditary monogenic diseases characterized by a low or absent production of adult hemoglobin and excess in the content of α-globin. This excess is cytotoxic for the erythroid cells and responsible for the β-thalassemia-associated ineffective erythropoiesis. Therefore, the decrease in excess α-globin is a relevant clinical effect for these patients and can be realized through the induction of fetal hemoglobin, autophagy, or both.

Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: a nationwide registry study from the Italian Medicines Agency.

In this analysis we describe the effectiveness of first-line ibrutinib in 747 patients with chronic lymphocytic leukemia (CLL) and TP53 aberrations in a nationwide study with a 100% capture of patients who received the study drug. Median age was 71 years (range 32-95). An estimated treatment persistence rate of 63.

Expression of γ-globin genes in β-thalassemia patients treated with sirolimus: results from a pilot clinical trial (Sirthalaclin).

Introduction: β-thalassemia is caused by autosomal mutations in the β-globin gene, which induce the absence or low-level synthesis of β-globin in erythroid cells. It is widely accepted that a high production of fetal hemoglobin (HbF) is beneficial for patients with β-thalassemia. Sirolimus, also known as rapamycin, is a lipophilic macrolide isolated from a strain of that serves as a strong HbF inducer and .

Thalassaemia is paradoxically associated with a reduced risk of in-hospital complications and mortality in COVID-19: Data from an international registry.

Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 ± 16 years (48.

Efficacy and Safety of Teriparatide in Beta-Thalassemia Major Associated Osteoporosis: A Real-Life Experience.

Osteoporosis represents a relevant cause of morbidity in adult Thalassemia Major (TM) population. Antiresorptive drugs such as bisphosphonates were demonstrated effective in preventing bone loss. Teriparatide (TP) is an anabolic agent approved for osteoporosis management in the general population, but its use has been very limited in TM patients so far.

Impact of the preparation method of red cell concentrates on transfusion indices in thalassemia patients: A randomized crossover clinical trial.

Background: The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences.

Study Design And Methods: The effects of two types of RCC (RCC-A, RCC-B) on transfusion regime were compared in a non-blinded, prospective, randomized, two-period, and crossover clinical trial.

Dual-energy X-ray absorptiometry pitfalls in Thalassemia Major.

Background: Low mineral mass and reduced bone strength with increased fracture risk are the main causes of morbidity in Thalassemia Major (TM). The pathogenesis is multifactorial and includes ineffective erythropoiesis with medullary expansion, multiple endocrine dysfunctions, direct iron bone deposition, deferoxamine-induced bone dysplasia, and reduced physical activity associated with disease complications. Dual-energy X-ray absorptiometry (DXA) is the "gold standard" for bone mineral density (BMD) assessment and for bone strength and quality evaluation.

Spermatozoal DNA damage in patients with B thalassaemia syndromes.

Objective: to determine whether sperm DNA damage is increased in patients with beta-thalassaemia syndromes.

Design: prospective comparative assessment of sperm genomic integrity in thalassaemia patients and donor controls and correlation of sperm DNA damage with other measures of semen quality, reproductive hormones, ferritin, zinc and vitamin E levels.

Setting: Thalassaemia Centre of Paediatric and Adolescent Unit, Ferrara, Italy and Academic Research Institutions in the UK.

Chelation therapy and bone metabolism markers in thalassemia major.

The aim of our study was to investigate the effects of subcutaneous desferrioxamine (DFX) and oral deferiprone (L1) therapy on bone metabolism markers in patients with thalassemia major. We studied 17 patients with thalassemia receiving long-term treatment with desferrioxamine, 20 patients receiving long-term treatment with deferiprone, and 15 healthy age-matched controls. The following investigations were performed: a) intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] as endocrine parameters; b) alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), osteocalcin (OC); c) bone resorption biochemical markers in serum and urine pyridinium crosslinks: hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP); d) serum levels of cytokines and growth factors: transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF-I), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-a (TNFalpha); e) serum levels of IGF binding protein-3 (IGFBP-3).

Impact of long-term iron chelation therapy on growth and endocrine functions in thalassaemia.

A large number of children treated from the time of diagnosis with modern transfusion and chelation therapy are now entering early adolescence or early adulthood, and only now can we evaluate how many complications, secondary to iron overload, can be prevented by daily s.c. desferrioxamine (DFX) therapy.

Healing of leg ulcers with hydroxyurea in thalassaemia intermedia patients with associated endocrine complications.

We report a preliminary clinical experience in the use of hydroxyurea (HU) for the treatment of leg ulcers in thalassaemia intermedia patients with associated endocrine complications. We administered HU 1 g/day to 6 adult patients with thalassaemia intermedia for 90 days. We observed an improvement (3 patients) or healing (3 patients) of chronic leg ulcers.

Paraplegia due to spinal cord compression by extramedullary erythropoietic tissue in a thalassaemia intermedia patient with gynecomastia secondary to cirrhosis: successful treatment with hydroxyurea.

We report a 24 years old patient with thalassaemia intermedia and gynecomastia, complicated by paraplegia and urinary/fecal incontinence due to spinal cord compression by an extramedullary erythropoiesis (EE) mass, treated with long-term hydroxyurea (HU). Neurological improvement occurred during the first 6 weeks of HU therapy (1,000 mg/day) and magnetic resonance imaging showed a reduction in EE mass. HU dosage was reduced to 500 mg/day after 5 months, and treatment was discontinued after 25 months.

Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center.

Two hundred and seventy-three patients with thalassaemia major (TM) were followed in the Ferrara Thalassaemia Centre over a thirty-year period. Forty-two patients had insulin dependent diabetes mellitus (IDDM). The first case was diagnosed in 1973.

HCV and HGV infection, iron overload and liver disease in multitransfused patients with thalassaemia and persistently normal or abnormal transaminase levels.

Prevalence and influence on liver disease of HCV and HGV infections, and HCV genotypes were studied in 28 HCV-Ab positive multitransfused thalassaemia patients with persistently normal ALT levels (group A) matched by sex and age with 28 patients with increased ALT levels (group B). Laboratory and virologic tests (all patients), liver biopsy (28 patients) and LIC by SQUID (30 patients) were performed. In group A, HCV-RNA was positive in 39%, genotype 2a was detected in 91%.

Left ventricular remodeling, systolic function, and diastolic function in young adults with beta-thalassemia intermedia: a Doppler echocardiography study.

Background: The aim of this study was to investigate the left ventricular (LV) remodeling and function in 24 asymptomatic young adults affected by beta-thalassemia intermedia (TI), in order to compare the obtained data with that of 80 patients affected by beta-thalassemia major (TM) and 65 healthy subjects.

Methods: LV volumes and shapes, mass index, mass/volume ratio, systolic and diastolic function, stroke volume, and cardiac index were determined by two-dimensional and M-mode echocardiography.

Results: In the TM and TI groups, LV volumes, diastolic and systolic shapes were significantly different from the control subjects, but the ejection fraction was slightly reduced only in the TM group.