Cooley's original description of beta-thalassaemia major included marked bone deformities as a characteristic feature. These were thought to be due to expansion of haemopoiesis attempting to compensate for the congenital anaemia. Regular blood transfusions from infancy prevents these skeletal problems. Nevertheless, symptoms due to bone disease frequently occur in adult patients. Osteoporosis has not previously been reported as a cause of severe morbidity in thalassaemia major. The present study shows a high prevalence of low bone mass among thalassaemia major patients and analyses the predisposing causes. Bone density scans were performed in 82 patients with transfusion-dependent beta thalassaemia. Factors known to be associated with low bone mass such as gender, endocrine disorders and lifestyle activities, together with factors specific to the thalassaemia and its management, were included in a series of univariate analyses to ascertain any significant associations. 42 (51%) of the patients had severely low bone mass and a further 37 (45%) had low bone mass. The three factors showing a statistically significant association with severely low bone mass were male sex, 24/38 (63%) males had severely low bone mass, compared with 18/44 (41%) females, the lack of spontaneous puberty, 22/32 (69%) who required therapeutic induction of pubertal development had severely low bone mass, compared with 19/47 (40%) with spontaneous puberty and diabetes, 8/10 (80%) diabetic patients had severely low bone mass, compared with 23/56 (41%) with normal glucose tolerance. There was no association between the bone mineral density measurements and the haematological characteristics or treatment details of these patients. Severely low and low bone mass are common findings in patients with beta-thalassaemia major despite optimal transfusion and iron chelation. The associated features suggest that the severely low bone mass is due to endocrine abnormalities, in contrast to the haematological causes of bone disease characteristically seen in untreated thalassaemics.

Objectives To examine the pregnancies, mode of delivery and outcomes, review the literature on fertility and discuss preconceptual guidance for women with β thalassaemia major. Design An observational study. Subjects Sixteen women with p thalassaemia major. Setting Two collaborating London teaching hospitals. Main outcome measures Pre‐pregnancy assessment, pregnancy course, mode of delivery, gesta‐tional age at delivery and birthweight. Results There were 16 pregnancies in 11 women. Three of these pregnancies were terminated. Of the 13 deliveries, there were two normal deliveries, one forceps delivery and 10 caesarean sections. The main findings in a further five women seeking fertility treatment were of hypogonadotrophic hypogonadism, diabetes and cardiomyopathy. Conclusions Pregnancy in women with p thalassaemia major does not appear to have a deleterious effect on the course of the disease. No increased obstetric complications were encountered except for the high caesarean section rate, essentially due to cephalopelvic disproportion. A high incidence of cardiomyopathy and diabetes dictates a careful assessment before embarking on ovulation induction to treat the hypogonadotrophic hypogonadism which is common in these women.

The incidence of endocrine dysfunction in relation to the detailed genotype of β‐thalassaemia is investigated in this study. In addition, the association of genotype to specific clinical features of β‐thalassaemia is examined, together with the relationship between serum ferritin levels and endocrine complications. Ninety‐seven patients were included, all with transfusion dependent β‐thalassaemia. Patients were divided into 2 categories; group 1 consisted of patients with a β0/β0 genotype with or without a concomitant α‐globin gene deletion as well as patients with β0/β+ or β+/β+ genotype and normal α‐globin chain synthesis. Group 2 included patients with β+/β+ or β+/β0 genotype and one α‐globin chain deletion and those with a moderate amount of β‐globin chain synthesis (β++) and normal α‐globin chain synthesis. The results showed that group 1 patients were more likely to have severe clinical disease (p = 0.005). Sixty‐four patients (66%) had at least 1 endocrine disorder and 39 (40%) had multiple endocrinopathies; the most common abnormality was hypogonadotrophic hypogonadism (HH). There was a significant association between patients with group 1 genotypes and the presence of HH and impaired glucose tolerance or diabetes. A positive correlation was demonstrated between serum ferritin concentrations and the presence of thyroid or parathyroid dysfunction.

Hepatitis C infection is common in patients receiving life-long blood transfusion therapy. Interferon-alpha induces long-term viral clearance in 25-30% of patients suffering from Cooley's anemia. Ribavirin, an orally active guanoside analogue together with interferon-alpha produces a sustained response in up to 40% of patients with cirrhosis, who had previously failed single agent treatment. Growth retardation in iron-overloaded patients is the result of growth hormone deficiency in up to 30% of patients. Height gain can be successfully achieved in these patients with growth hormone treatment. Pregnancy in women with Cooley's anemia is now a reality, and over 100 pregnancies have been documented. Conception may be spontaneous or the result of ovulation induction. Cardiomyopathy and diabetes require careful assessment in these patients before a decision is made to treat with gonadotrophins to induce ovulation.

Background:The prevalence and importance of cardiac dysfunction in critically ill patients with COVID-19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID-19 in intensive care in Sweden. Methods:This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction). Results:We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and | 607 HOLMQVIST eT aL.

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We report semen analyses in eight patients with beta-thalassaemia major, with poor results in all but the youngest. The causation is multi-factorial, with iron deposition in the pituitary gland resulting from life-long dependence on blood transfusions being a major factor. We speculate on other contributing causes, but further research is required to elucidate these. Improving haematological care means that these men are increasingly surviving to adult life. Relevant techniques to enable them to achieve their desire for fatherhood are considered.

Introduction: The importance of cardiac dysfunction in critically ill patients with COVID-19 is not well studied. The aim of the study was to assess the incidence, clinical risk factors, and prognosis of cardiac dysfunction in critical illness caused by COVID-19, and to evaluate if cardiac biomarkers can detect this condition.Methods: This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 hours from admission to the ICU and again after four to seven days. Cardiac biomarkers and clinical data were collected at the time of echocardiography. Cardiac dysfunction was defined as either left ventricular (LV) dysfunction (having an ejection fraction < 50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (having a tricuspid annular plane systolic excursion (TAPSE) < 17mm or a moderate/severe RV dysfunction assessed visually).Results: We included 132 patients of whom 94 (71%) were included prospectively. The vast majority were intubated (n=127). At the time of admission to ICU, 35 (27%) patients had cardiac dysfunction and 7 patients (5%) had cardiac dysfunction detected later in the ICU-period. LV dysfunction was found in 18 patients and RV dysfunction in 17 patients, 7 patients had both RV and LV dysfunction. Noradrenaline > 0.20µg/kg/min was the only clinical variable associated with a higher risk of cardiac dysfunction. RV dysfunction was associated with an increased risk of death in a risk-adjusted model (OR 3.98, p = 0.013). Troponin and N-terminal pro b-type natriuretic peptide (NTproBNP) had moderate values in detecting cardiac dysfunction (AUC 0.729 and AUC 0.744, respectively). A combination of troponin < 1.44 times the upper reference limit and NTproBNP < 857ng/L had 85% probability of excluding cardiac dysfunction.Conclusions: Cardiac dysfunction is common in critically ill patients with COVID-19. Although not easily detected with clinical variables, cardiac biomarkers might be helpful. RV dysfunction is associated with an increased risk of death, these patients might benefit from further investigation or treatments. Trial registration: Registered on 24 Aug 2020 at Clinicaltrials.gov; registration number NCT04524234.