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Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload that requires chelation to levels below the threshold associated with complications. This can take several years in patients with high iron burden, highlighting the value of long-term chelation data. Here, we report the 1-year extension of the THALASSA trial assessing deferasirox in NTDT; patients continued with deferasirox or crossed from placebo to deferasirox. Of 133 patients entering extension, 130 completed. Liver iron concentration (LIC) continued to decrease with deferasirox over 2 years; mean change was −7.14 mg Fe/g dry weight (dw) (mean dose 9.8 ± 3.6 mg/kg/day). In patients originally randomized to placebo, whose LIC had increased by the end of the core study, LIC decreased in the extension with deferasirox with a mean change of −6.66 mg Fe/g dw (baseline to month 24; mean dose in extension 13.7 ± 4.6 mg/kg/day). Of 166 patients enrolled, 64 (38.6 %) and 24 (14.5 %) patients achieved LIC <5 and <3 mg Fe/g dw by the end of the study, respectively. Mean LIC reduction was greatest in patients with the highest pretreatment LIC. Deferasirox progressively decreases iron overload over 2 years in NTDT patients with both low and high LIC. Safety profile of deferasirox over 2 years was consistent with that in the core study.

SARS-CoV-2 infection is characterized by a protean clinical picture that can range from asymptomatic patients to life-threatening conditions. Severe COVID-19 patients often display a severe pulmonary involvement and develop neutrophilia, lymphopenia, and strikingly elevated levels of IL-6. There is an over-exuberant cytokine release with hyperferritinemia leading to the idea that COVID-19 is part of the hyperferritinemic syndrome spectrum. Indeed, very high levels of ferritin can occur in other diseases including hemophagocytic lymphohistiocytosis, macrophage activation syndrome, adult-onset Still’s disease, catastrophic antiphospholipid syndrome and septic shock. Numerous studies have demonstrated the immunomodulatory effects of ferritin and its association with mortality and sustained inflammatory process. High levels of free iron are harmful in tissues, especially through the redox damage that can lead to fibrosis. Iron chelation represents a pillar in the treatment of iron overload. In addition, it was proven to have an anti-viral and anti-fibrotic activity. Herein, we analyse the pathogenic role of ferritin and iron during SARS-CoV-2 infection and propose iron depletion therapy as a novel therapeutic approach in the COVID-19 pandemic.

In this large, prospective study of persons of northern European ancestry living in Australia, 1 in 146 was homozygous for a mutation (C282Y) in the HFE gene that is associated with hereditary hemochromatosis. Disease related to iron overload developed in 28% of male homozygotes but in only 1% of female homozygotes. In persons homozygous for a mutation (C282Y) in the HFE gene that is associated with hereditary hemochromatosis, disease related to iron overload developed in 28% of male homozygotes but in only 1% of female homozygotes. Hereditary hemochromatosis is an inherited condition of dysregulated iron absorption that can lead to total-body iron overload with secondary tissue damage in a wide range of organs. Left untreated, this condition can result in diseases such as hepatic cirrhosis and hepatocellular carcinoma. 1 , 2 Disease can be prevented by decreasing the body's iron stores, through either regular blood donation or therapeutic venesection. 3 , 4 Cirrhosis most commonly occurs in patients with a homozygous substitution of tyrosine for cysteine at position 282 (C282Y) in the HFE protein who have serum ferritin levels of more than 1000 μg per liter. 4 , 5 Patients with hereditary . . .

Disease-related complications and management are different among patients with thalassemia. This study was aimed to review the prevalence, clinical risk factors for the complications and the management in patients with thalassemia in Thailand. A multicenter cross-sectional study was conducted in patients with thalassemia aged ≥ 18 years old. Thalassemia-related complications and management were reviewed. The clinical parameters significantly associated with the complications were analyzed by logistic regression methods. The prevalence of thalassemia-related complications was 100% in patients with transfusion-dependent thalassemia (TDT) and 58.8% in patients with non-transfusion-dependent thalassemia (NTDT). Advanced age was statistically associated with extramedullary hematopoiesis in both TDT and NTDT patients. Splenectomy was a significant risk factor for pulmonary hypertension in both groups of patients. Severe iron overload started earlier in patients with TDT than NTDT and was associated with diabetes mellitus (adjusted odds ratio (AOR) = 6.2, p-value = 0.02). Disease-related complications are more prevalent in patients with TDT than patients with NTDT. Splenectomy and advanced age were important risk factors for developing major complications in both groups. Early screening and management for specific disease-related complications should be considered in patients with thalassemia according to their clinical risk factors.

Mutations in the HFE gene are associated with hemochromatosis. In this large study of an ethnically and racially diverse population, homozygosity for C282Y mutations in the HFE gene was more common in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Most C282Y homozygotes had elevated serum ferritin levels and transferrin saturation. In this large study of an ethnically and racially diverse population, homozygosity for C282Y mutations in the HFE gene was more common in non-Hispanic whites (0.44 percent) than in Native Americans, Hispanics, blacks, Pacific Islanders, or Asians. Iron overload can be associated with a wide range of genetic and environmental factors and can lead to parenchymal damage of organs. Homozygosity for the C282Y mutation of the HFE gene is associated with susceptibility to iron overload and is a common genetic mutation, occurring in 0.3 to 0.5 percent of white persons of northern European descent. 1 , 2 Phlebotomy treatment can prevent some of the major complications of iron overload, and patients have normal life expectancy if they are treated before organ damage occurs. 3 Iron overload can occur in nonwhites and may be related to as-yet-undiscovered genetic mutations, environmental factors, . . .

Purpose To explore the prevalence of hypoparathyroidism (HPT), overt and subclinical, in a cohort of adults with Iron Overload Diseases (IOD). Secondary aim was to test the calcium (Ca)-to-phosphorus (P) ratio performance in identifying HPT. Methods Single-center, prospective, case-control study. Sixty-five IOD, 40 with thalassemia major/intermedia (TMI) and 25 with hemochromatosis (HC), and 76 age-matched controls were included. Main outcomes (serum Ca, P, Ca/P ratio, intact parathyroid hormone (PTH), albumin) defined overt and subclinical HPT. Results Albumin-adjusted Ca was lower (p = 0.004) and P higher (p = 0.002) comparing IOD to controls. Ca/P ratio was lower in IOD than controls (p < 0.001); PTH did not change. P was higher and Ca/P lower comparing TMI to HC and controls (p < 0.001); Ca did not change. A total of 28/65 IOD (43%) had HPT (9.2% overt, 33.8% subclinical) whose prevalence was higher in TMI than HC (p < 0.001). Ca/P ratio <2.32 had sensitivity 71.4% and specificity 83.9% in detecting overt/subclinical HPT. IOD with Ca/P ratio <2.32 (1.78 in SI) had an almost 12-fold increased likelihood to be affected by HPT (OR 12.92 [3.90–42.82]; p < 0.001). Ca/P (p = 0.002) was the only independent risk factor for HPT at multivariate analysis. Conclusions HPT, especially non-classical subclinical HPT, is common in adult IOD with higher prevalence in TMI than HC. Ca/P ratio <2.32 is accurate to screen for overt/subclinical HPT and should be periodically evaluated in IOD to early detect an unbalanced mineral metabolism, and to monitor a possible evolution from subclinical to overt HPT.

Background: Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference.Methods: Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes.Results: According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes.Conclusion: IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

BackgroundSlight to moderate hepatic iron overload (HIO) can be found in cases of liver disease, including non-alcoholic fatty liver disease (NAFLD), but the mechanism is not completely understood, as well as its relationship with obesity.ObjectiveTo determine the prevalence of HIO assessed through histopathological examination in obese individuals undergoing bariatric surgery and to identify correlations between this condition and demographic, anthropometric, clinical, laboratory, and NAFLD-related aspects.MethodsThis is a cross-sectional study which enrolled individuals undergoing bariatric surgery from January 2018 to February 2019 at a tertiary university hospital. NAFLD and HIO were assessed through histological examination.ResultsOf 125 individuals, 87.2% were female and the average age was 38.8 ± 9.2 years. The average BMI was 37.2 ± 3.1 kg/m2. NAFLD was present in 66.4% and HIO in 17.6%, with 63.6% of patients with overload classified as mild (grade I) and 22.7% moderate (grade II). HIO was significantly more frequent in males (p = 0.003) and was significantly associated with higher levels of glucose (92.1 ± 28.4 vs. 80.7 ± 39.6; p = 0.02), ferritin (385.5 ± 290.9 vs. 131.6 ± 99.7; p < 0.0001), serum iron (82.4 ± 35.7 vs. 66.6 ± 25.1; p = 0.03), glutamic-oxaloacetic transaminase (27.3 ± 19.5 vs. 20.6 ± 8.8; p = 0.02), and glutamic-pyruvic transaminase (37.6 ± 36.4 vs. 24.6 ± 16.3; p = 0.01). Multivariate analysis showed that HIO intensity was significant and independently associated with ferritin levels (R = 0.19; p = 0.01), serum iron (R = 0.25; p < 0.0001), blood glucose (R = 0.16; p = 0.001), and total cholesterol (R = − 0.17; p < 0.0001).ConclusionIn obese individuals, HIO presented a high prevalence and was associated with higher levels of ferritin, serum iron, glucose, and transaminases; lower levels of total cholesterol; and male gender.