Serum progranulin levels in paediatric patients with Gaucher disease; relation to disease severity and liver stiffness by transient elastography.

BACKGROUND: Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis. OBJECTIVES: We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE. METHODS: Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded. RESULTS: By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = -.529, P < .001), liver volume (r = -.298, P = .034) and liver stiffness (r = -.652, P < .001). CONCLUSIONS: Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.

Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with ß-thalassemia major.

BACKGROUND: Disturbances of glucose metabolism are common in ß-thalassemia major (ß-TM). AIM: This study was conducted to assess the pattern of glucose homeostasis in pediatric ß-TM patients comparing oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS). METHODS: Two-hundred ß-TM patients were studied and those with random blood glucose (RBG) ≥7.8 mmol/L (140 mg/dL) were subjected to OGTT, insertion of CGMS and measurement of fasting C peptide, fasting insulin, and hemoglobin A1c (HbA1c). RESULTS: Twenty patients (10%) had RBG ≥ 7.8 mmol/L. Using OGTT, 6 out of 20 patients (30%) had impaired glucose tolerance (IGT) while 7 (35%) patients were in the diabetic range. CGMS showed that 7/20 (35%) patients had IGT and 13 (65%) patients had diabetes mellitus (DM); 10 of the latter group had HbA1c readings within diabetic range. The percentage of diabetic patients diagnosed by CGMS was significantly higher than that with OGTT (P = 0.012). Serum ferritin was the only independent variable related to elevated RBG. All ß-TM patients with DM were non-compliant to chelation therapy. CONCLUSIONS: The use of CGMS in the diagnosis of early glycemic abnormalities among pediatric patients with ß-TM appears to be superior to other known diagnostic modalities.

Management of Children With ß-Thalassemia Intermedia: Overview, Recent Advances, and Treatment Challenges.

Our knowledge of the various clinical morbidities that thalassemia intermedia (TI) patients endure has substantially increased over the past decade. It is mandatory to grasp a solid understanding of disease-specific complications in order to tailor management. The optimal course of management for TI patients has been hard to identify, and several controversies remain with regard to the best treatment plan. Although advances in TI are moving at a fast pace, many complications remain with no treatment guidelines. Studies that expand our understanding of the mechanisms and risk factors, as well as clinical trials evaluating the roles of available treatments, will help establish management guidelines that improve patient care. Novel therapeutic modalities are now emerging. This article focuses on the management of children with ß-TI. We present various clinical morbidities and their association with the underlying disease pathophysiology and risk factors. All therapeutic options, recent advances, and treatment challenges were reviewed.

Enhancement of the antidermatophytic activity of silver nanoparticles by Q-switched Nd:YAG laser and monoclonal antibody conjugation.

The objective of this research was to investigate the effect of silver nanoparticles (AgNPs), free or conjugated with monoclonal antibody and mediated by Q-switched Nd:YAG laser on five dermatophytes. The laser was applied for 45 s at 532 nm and 0.8 J/cm2. The application of AgNPs combined with laser caused an increase in fungal susceptibility compared to application of AgNPs alone. The MIC50 and MIC100 recorded 3 and 9 µg/ml in the case of E. floccosum (the most susceptible species), 10 and 19 µg/ml for T. rubrum (the most tolerant species), respectively. A decrease in keratinase activity reaching 76.1, 67.1, and 62.4% was attained in the case of M. gypseum, T. rubrum, and T. mentagrophyte, respectively, on application of 10 µg/ml AgNPs combined with Nd:YAG laser. Under the same conditions of application, a steady increase in leaked materials coupled with reduction in ergosterol synthesis was reached. The structural alterations occurred to the fungus were more observed on the application of AgNPs in combination with laser where the conidia and hyphae lost their cellular integrity, become flaccid, permanently destructed, and completely killed. The monoclonal antibody conjugated AgNPs did not result in significant variation in in vitro experiments compared with that produced by nonconjugated nanoparticles. However, the conjugates achieved significantly more curing of M. canis-inoculated guinea pigs compared with nonconjugated nanoparticles.

Expression of CD4+ CD28null T lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness.

BACKGROUND: Cardiovascular risk in type 1 diabetes mellitus (T1DM) is associated with endothelial dysfunction, inflammation, and altered immunity. CD4+ CD28null T-cells are a subset of long-lived cytotoxic CD4+ T-lymphocytes with proatherogenic and plaque-destabilizing properties. We hypothesized that the frequency of CD4+ CD28null T-cells may be altered in T1DM and related to vascular complications. AIM: To assess the percentage of CD4+ CD28null T-lymphocytes in children and adolescents with T1DM and their relation to vascular structure and glycemic control. METHODS: Totally 100 patients with T1DM were divided into 2 groups according to the presence of microvascular complications and compared with 50 healthy controls. CD4+ CD28null T-lymphocytes were analyzed using flow cytometry. Aortic elastic properties and carotid intima media thickness (CIMT) were assessed. RESULTS: Aortic stiffness index and CIMT were significantly higher among patients compared with healthy controls while aortic strain and distensibility were decreased. The percentage of CD4+ CD28null T-cells was significantly higher in patients with and without microvascular complications compared with controls. High frequency of CD4+ CD28null T-cells was found among patients with microalbuminuria or peripheral neuropathy. Patients with CD4+ CD28null T-cells ≥10% had higher HbA1c, urinary albumin creatinine ratio, aortic stiffness, and CIMT. CD4+ CD28null T-cells were positively correlated to HbA1c, aortic stiffness index, and CIMT. CONCLUSIONS: Changes in aortic elastic properties and increased CIMT among young patients with T1DM may enable the recognition of preclinical cardiac impairment. The correlation between CD4+ CD28null T-cells and assessed parameters of vascular structure highlights the role of altered immune response in the occurrence of diabetic vascular complications.

Soluble Fas/FasL ratio as a marker of vasculopathy in children and adolescents with sickle cell disease.

OBJECTIVES: Sickle cell disease (SCD) is characterized by chronic inflammation due to ischemic tissue damage, accentuated during acute complications. Fas and its ligand (FasL) are members of tumor necrosis factor receptor superfamily and a major pathway for induction of apoptosis. Fas/FasL interactions may be related to augmentation of inflammatory response. We assessed the levels of sFas and sFasL in 35 children and adolescents with SCD compared with 35 healthy controls in relation to hemolysis, iron overload, sickle vasculopathy including kidney disease. METHODS: SCD patients, in steady state and asymptomatic for pulmonary hypertension, were studied stressing on hydroxyurea therapy, serum ferritin, urinary albumin creatinine ratio (UACR), high-sensitivity C-reactive protein (hs-CRP) and sFas/sFasL levels. RESULTS: sFas/sFasL ratio was significantly higher in patients compared with controls. sFas/sFasL ratio was elevated in patients with pulmonary hypertension, nephropathy and those who had history of frequent sickling crisis or serum ferritin ⩾2500. SCD patients treated with hydroxyurea had lower sFas/sFasL ratio than untreated patients. sFas/sFasL ratio was positively correlated to transfusion index, white blood cells, hs-CRP, serum ferritin and UACR. The cutoff value of sFas/sFasL at 8.75pg/mL could differentiate SCD patients with and without nephropathy while the cutoff value at 22pg/mL could differentiate SCD patients with and without pulmonary hypertension risk with high sensitivity and specificity. CONCLUSION: sFas/sFasL ratio may be considered as a marker for vascular dysfunction in SCD patients and is related to inflammation, iron overload and albuminuria level. Thus, it may be a reliable method to assess renal impairment in SCD.

Endothelial monocyte activating polypeptide II in children and adolescents with type 1 diabetes mellitus: Relation to micro-vascular complications.

OBJECTIVES: Endothelial monocyte-activating polypeptide II (EMAP II) is a multifunctional polypeptide with proinflammatory and antiangiogenic activity. Hyperglycemia and dyslipidemia appears to be significant factors contributing to increased EMAP-II levels. We determined serum EMAP II in children and adolescents with type 1 diabetes as a potential marker for micro-vascular complications and assessed its relation to inflammation and glycemic control. METHODS: Eighty children and adolescents with type 1 diabetes were divided into 2 groups according to the presence of micro-vascular complications and compared with 40 healthy controls. High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c) and EMAP II levels were assessed. RESULTS: Serum EMAP II levels were significantly increased in patients with micro-vascular complications (1539 ± 321.5 pg/mL) and those without complications (843.6 ± 212.6 pg/mL) compared with healthy controls (153.3 ± 28.3 pg/mL; p<0.001). EMAP II was increased in patients with microalbuminuria than normoalbuminuric group (p<0.001). Significant positive correlations were found between EMAP II levels and body mass index, fasting blood glucose, HbA1c, serum creatinine, triglycerides, total cholesterol, urinary albumin creatinine ratio (UACR) and hs-CRP (p<0.05). A cutoff value of EMAP II at 1075 pg/mL could differentiate diabetic patients with and without micro-vascular complications with a sensitivity of 93% and specificity of 82%. CONCLUSIONS: We suggest that EMAP II is elevated in type 1 diabetic patients, particularly those with micro-vascular complications. EMAP II levels are related to inflammation, glycemic control, albuminuria level of patients and the risk of micro-vascular complications.

Cultural preferences and limited public resources influence the spectrum of thalassemia in Egypt.

BACKGROUND: Cultural beliefs of Egyptians with respect to the origin of thalassemia and its prevention, as well as national resources available for care, often differ from those of Western countries. OBJECTIVES: To assess the impact of cultural attitudes and the effect of limited medical and financial resources that could affect the management of Egyptian thalassemic patients. SUBJECTS: A cross sectional study included 205 Egyptians ß-thalassemia major (ß-TM) patients, with a mean age of 149±87.90 months and a male to female ratio of 94:111. METHODS: Demographic data stressing on order of birth, consanguineous marriage, and family history of ß-TM, transfusion, and chelation therapy, were reported. HCV-Ab, HBV-Ag, and complete blood count were recorded with calculation of mean pretransfusional hemoglobin. RESULTS: The age distribution was relatively nonhomogenous, with 39% of patients between 10 and 20 years of age and 16% were younger than 5. There were high family birth rates and 35% of patients were third or more in order of birth and a marked cultural preference for consanguineous marriage, representing 61% of all the parents' marriages, as well as a high rate (59.5%) of a positive family history of ß-TM. Patients transfused on low pretransfusion hemoglobin levels around 8 g/dL, and those receiving blood transfusion before the establishment of National Blood Transfusion Services showed a statistically significant higher rate of positive hepatitis B and C viral infections. Chelation therapy tended to start at late age, mean age was around 4 years. Before 2000, subcutaneous deferoxamine was the most widely used chelation, and since then a considerable number of patients (50%) had started to use oral iron chelators. CONCLUSIONS: The strong cultural preferences for consanguineous marriage and limited preventive programmes and resources have had a negative impact on the management of Egyptians thalassemic patients.

One-Year Prospective Study of Community Acquired Influenza and Parainfluenza Viral Infections in Hospitalized Egyptian Children with Malignancy: Single Center Experience.

BACKGROUND: Respiratory viruses are widespread in the community and easily transmitted to immunocompromised patients. AIMS: Assess the prevalence of community-acquired respiratory viral infections among children with cancer presenting with clinical picture suggestive of lower respiratory tract infections (LRTIs), and evaluate its risk factors and prognosis. METHODS: Over a year, 90 hospitalized children with malignancy and LRTIs recruited, subjected to clinical assessment, investigated through hematology panel, blood culture, chest x-ray, CT chest and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses, and respiratory syncytial virus (RSV), and prospectively followed up for the clinical outcome. RESULTS: Viral pathogens were identified in 34 patients (37.7%), with a seasonal peak from April to May. The most frequently detected virus was influenza virus [type A (16 cases; 47%), type B (4 cases; 12%)] followed by parainfluenza virus [PIV1 (9 cases; 26%), PIV3 (3 cases; 15%)], and none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed infections [bacterial/viral and bacterial/fungal] in 13, and 36 cases had unidentified etiology. The majority of patients with influenza and parainfluenza infections had hematological malignancy, presented with fever, and had mild self-limited respiratory illness. Five patients with mixed viral and bacterial infection had severe symptoms necessitating ICU admission. Six patients died from infection-related sequelae; two had mixed PIV and Staphylococcal infections. CONCLUSIONS: Community acquired influenza and parainfluenza infections are common in pediatrics patients with malignancy, either as isolated or mixed viral/bacterial infections. Clinical suspicion is essential as hematological and radiological manifestations are nonspecific. Rapid diagnosis and management are mandatory to improve patients' outcome.

Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis.

OBJECTIVE: Triggering receptor expressed on myeloid cells-1 (TREM-1) is an important receptor involved in the innate inflammatory response and sepsis. We assessed soluble TREM-1 (sTREM-1) in 112 septic neonates (63 culture-positive and 49 culture-negative) and 40 healthy controls as a potential early diagnostic and prognostic marker for neonatal sepsis (NS). METHODS: Studied neonates were evaluated for early- or late-onset sepsis using clinical and laboratory indicators upon admission. sTREM-1 was measured on initial sepsis evaluation and at 48h after antibiotic therapy. For ethical reasons, cord blood samples were collected from control neonates and only samples from neonates that proved to be healthy by clinical examination and laboratory analysis were further analyzed for sTREM-1. RESULTS: Baseline sTREM-1 levels were significantly elevated in culture-proven (1461.1±523pg/mL) and culture-negative sepsis (1194±485pg/mL) compared to controls (162.2±61pg/mL) with no significant difference between both septic groups. Culture-positive or negative septic preterm neonates had significantly higher sTREM-1 compared to full term neonates. sTREM-1 was significantly higher in neonates with early sepsis than late sepsis and was associated with high mortality. sTREM-1 was significantly decreased 48h after antibiotic therapy compared to baseline or levels in neonates with persistently positive cultures. sTREM-1 was positively correlated to white blood cells (WBCs), absolute neutrophil count, immature/total neutrophil (I/T) ratio, C-reactive protein (hs-CRP) and sepsis score while negatively correlated to gestational age and weight. hs-CRP and sepsis score were independently related to sTREM-1 in multiregression analysis. sTREM-1 cutoff value of 310pg/mL could be diagnostic for NS with 100% sensitivity and specificity (AUC, 1.0 and 95% confidence interval [CI], 0.696-1.015) while the cutoff value 1100pg/mL was predictive of survival with 100% sensitivity and 97% specificity (AUC, 0.978 and 95% CI, 0.853-1.13). However, hs-CRP cutoff 13.5mg/L could be diagnostic for NS with a sensitivity of 76% and specificity of 72% (AUC, 0.762 and 95% CI, 0.612-0.925) and levels were not related to survival as no significant difference was found between dead and alive septic neonates. CONCLUSIONS: Elevated sTREM-1 could be considered an early marker for NS that reflects sepsis severity and poor prognosis.

Flow cytometric assessment of circulating platelet and erythrocytes microparticles in young thalassemia major patients: relation to pulmonary hypertension and aortic wall stiffness.

Heart disease is the leading cause of mortality and morbidity in ß-thalassemia major (ß-TM). Aggregability of abnormal red cells and membrane-derived microparticles (MPs) stemming from activated platelets and erythrocytes are responsible for thrombotic risk. We measured platelet and erythrocyte MPs (PMPs and ErMPs) in 60 young ß-TM patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on transfusion history, splenectomy, thrombotic events, chelation therapy, hematological and coagulation profiles, flow cytometric measurement of PMPs (CD41b(+) ) and ErMPs (glycophorin A(+) ) as well as echocardiographic assessment of aortic elastic properties. Aortic stiffness index and pulmonary artery pressure were significantly higher, whereas aortic strain and distensibility were lower in TM patients than controls (P < 0.001). Both PMPs and ErMPs were significantly elevated in TM patients compared with controls, particularly patients with risk of pulmonary hypertension, history of thrombosis, splenectomy or serum ferritin >2500 µg/L (P < 0.001). Compliant patients on chelation therapy had lower MPs levels than non-compliant patients (P < 0.001). PMPs and ErMPs were positively correlated to markers of hemolysis, serum ferritin, D-dimer, vWF Ag, and aortic stiffness, whereas negatively correlated to hemoglobin level and aortic distensibility (P < 0.05). We suggest that increased MPs may be implicated in vascular dysfunction, pulmonary hypertension risk, and aortic wall stiffness observed in thalassemia patients. Their quantification could provide utility for early detection of cardiovascular abnormalities and monitoring the biological efficacy of chelation therapy.

Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young ß-thalassemia intermedia patients.

OBJECTIVE: To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in ß-thalassemia intermedia (TI) patients compared with single HU therapy. METHODS: An interventional prospective randomized study registered in the ClinicalTrials.gov (NCT01624038) was performed on 80 TI patients (≤ 18 yr) divided into group A (40 patients received combined HU and rHuEPO) and group B (40 patients received single HU therapy). Baseline serum EPO levels were measured, and both groups were followed up for a mean period of 1 yr with regular assessment of transfusion requirements, blood pressure, ferritin, liver and renal functions, hemoglobin, and HbF. Quality of life (QoL) was assessed at the start and end of the study. RESULTS: Transfusion frequency and index were significantly decreased, while QoL was increased in group A compared with group B where 85% of patients showed improvement on combined therapy compared with 50% of patients on HU. Hemoglobin and HbF were significantly increased in both TI groups; however, this was more evident in group A than in group B. Also, 37.5% of patients in group A became transfusion-independent compared with 15% in group B. EPO levels were negatively related to increments of hemoglobin and HbF. Splenectomized patients and those with initial HbF% >40% had the best response to combined therapy. No serious adverse events necessitating discontinuation of therapy in both groups. CONCLUSIONS: HU was effective in management of TI; however, combination with rHuEPO gave a superior therapeutic effect resulting in the best clinical and hematological responses without adverse events.

Effect of antioxidant therapy on hepatic fibrosis and liver iron concentrations in ß-thalassemia major patients.

To assess the effects of combined vitamin therapy on oxidant-antioxidant hepatic status and hemoglobin (Hb) derivatives on ß-thalassemia major (ß-TM), a prospective study of 60 ß-TM patients aged 4 to 17 years, was conducted. Thirty-nine patients with initial low serum vitamins E, C and A, were treated with oral combined vitamins for 1 year compared to 21 patients with normal vitamin levels. Serum transaminases, serum ferritin, hepatic fibroscan elastography (TE) and magnetic resonance imaging R2* (MRI R2*) for liver iron concentration (LIC), were assessed before and after 6 and 12 months of therapy. Antioxidant capacity was assessed by levels of reduced glutathione (GSH), malondialdehyde (MDA), catalase, superoxide dismutase and GSH enzymes. The studied vitamins, reduced GSH and Hb levels were significantly elevated and paralleled by progressive decline in MDA and ferritin during therapy (p <0.001). Serum transaminase and superoxide dismutase were significantly decreased, while GSH reductase was significantly elevated during therapy (p <0.001). Improvement of hepatic fibrosis as 23.0% had TE (>12 kPa) at baseline compared to 20.5% after therapy (p >0.05), although LIC values were significantly decreased (p <0.001). Combined vitamin therapy improves the antioxidant/oxidant balance, LIC and hepatic fibrosis in young ß-TM patients.

Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years.

Long-term safety and efficacy data on the iron chelator deferiprone in sickle cell disease (SCD) and other anemias are limited. FIRST-EXT was a 2-year extension study of FIRST (Ferriprox in Patients With Iron Overload in Sickle Cell Disease Trial), a 1-year, randomized noninferiority study of deferiprone vs deferoxamine in these populations. Patients who entered FIRST-EXT continued to receive, or were switched to, deferiprone. Altogether, 134 patients were enrolled in FIRST-EXT (mean age: 16.2 years), with mean (SD) exposure to deferiprone of 2.1 (0.8) years over the 2 studies. The primary end point was safety. Secondary end points were change in liver iron concentration (LIC), cardiac T2∗, serum ferritin (SF), and the proportion of responders (≥20% improvement in efficacy measure). The most common adverse events considered at least possibly related to deferiprone were neutropenia (9.0%) and abdominal pain (7.5%). LIC (mg/g dry weight) decreased over time, with mean (SD) changes from baseline at each time point (year 1, -2.64 [4.64]; year 2, -3.91 [6.38]; year 3, -6.64 [7.72], all P < .0001). Mean SF levels (µg/L) decreased significantly after year 2 (-771, P = .0008) and year 3 (-1016, P = .0420). Responder rates for LIC and SF increased each year (LIC: year 1, 46.5%; year 2, 57.1%; year 3, 66.1%; SF: year 1, 35.2%; year 2, 55.2%; year 3, 70.9%). Cardiac T2∗ remained normal in all patients. In conclusion, long-term therapy with deferiprone was not associated with new safety concerns and led to continued and progressive reduction in iron load in individuals with SCD or other anemias. The trial was registered at www.clinicaltrials.gov as #NCT02443545.

D-dimer levels in type 1 and type 2 diabetic children and adolescents; Relation to microvascular complications and dyslipidemia "own data and review".

BACKGROUND: Changes in the coagulation cascade have been implicated in the pathogenesis of the vascular diabetic complications. OBJECTIVE: to assess D-dimer level (as a marker of coagulation cascade/fibrinolysis activation) in type 1 and type 2 diabetics and its correlation with microvascular complications and serum total cholesterol (TC) level. METHODS: Ninety patients were included divided into two groups. Group 1; comprised 50 type 1 diabetics with a mean age of 13.56 years. Their disease duration ranged between 0.4-16 years. Group 2; comprised 40 type 2 diabetics with a mean age of 13.5 years. Their disease duration ranged between 0.4-8 years. Patients were compared to 60 healthy age and sex matched subjects served as controls. Laboratory investigations included; fasting blood glucose, glycosylated hemoglobin, quantitative urinary albumin creatinine ratio (ACR), serum TC and measurement of plasma D-dimer levels. RESULTS: Type 2 diabetics had significantly higher weight and body mass index (BMI) Standard deviation score (SDS) (p<0.0001) compared to type 1 diabetics. Type 2 diabetics had higher TC (p<0.04) and D-dimer levels (p<0.05) compared to type 1 diabetics. D-dimer level was highly significantly elevated among type 1 diabetics with retinopathy, neuropathy and nephropathy compared to non-complicated patients (p<0.01). D-dimer was significantly correlated with ACR (p<0.001) in both studied groups. In type 2 diabetics, TC level was positively correlated with BMI SDS (p<0.05), D-dimer level was significantly correlated with disease duration (p<0.05), blood pressure (p<0.01), and TC (p<0.05). In type 1 diabetics, D-dimer levels were positively correlated with blood pressure (p<0.01). In both types, D-dimer is positively correlated with ACR (p<0.001). CONCLUSION: There was a tendency to hypercoagulability in both types of diabetes. This phenomenon may play a role in the development of diabetic microvascular complications.

Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study.

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

Clinicopathological and radiological study of Egyptian ß-thalassemia intermedia and ß-thalassemia major patients: relation to complications and response to therapy.

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian ß-thalassemia intermedia (ß-TI) patients were compared with 70 ß-thalassemia major (ß-TM) patients. ß-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, ß-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in ß-TM patients compared with ß-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for ß-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between ß-TI and ß-TM. We provide evidence that calls for the use of HU in ß-TI patients.

N-terminal natriuretic peptide and ventilation-perfusion lung scan in sickle cell disease and thalassemia patients with pulmonary hypertension.

The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 beta-thalassemia major (beta-TM) and 15 beta-thalassemia intermedia (beta-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 +/- 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, beta-TI and beta-TM patients, respectively. Pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. Pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators.

Spinal cord compression and extramedullary hematopoiesis in young Egyptian beta-thalassemia patients.

The problem of spinal cord compression (SCC) related to extramedullary hematopoiesis (EMH) in beta-thalassemia (beta-thal) patients, both clinically and radiologically and its correlation with laboratory parameters of anemia and hemosiderosis was assessed. Sixty beta-thal patients were included and divided into group I: 40 beta-thal major patients (beta-TM), aged 7-30 years with a mean age of 15 +/- 5.3 years, group II: 20 beta-thal intermedia patients (beta-TI) aged 6-20 years with a mean age of 13 +/- 4.6 years. They were subjected to neurological examination, thoracic and lumbosacral computed tomography (CT) and magnetic resonance imaging (MRI). Spinal EMH was found in 13.3% of the thalassemic patients with a higher incidence in beta-TI compared to beta-TM patients (p = 0.03). Evidence of spinal EMH was associated with higher serum ferritin (p < 0.0001), lower pre transfusion hemoglobin (Hb) (p = 0.002) and lower transfusion index (p = 0.01). Extramedullary hematopoiesis was more evident in young beta-TI patients, and was related to inadequate chelation, high serum ferritin and inadequate transfusion therapy.

Subclinical atherosclerosis in young beta-thalassemia major patients.

Subclinical atherosclerosis in young beta-thalassemia major (beta-TM) patients and its risk factors including dyslipidemia compared to type 1 diabetic patients were assessed. Ninety subjects were included and divided into three groups: group I comprised 30 beta-TM patients with a mean age of 18.4 +/- 6.18 years; group II comprised of 30 type 1 diabetic patients with a mean age of 19.23 +/- 4.25 years, and 30 healthy subjects served as controls in group III. Fasting lipid profiles, hemoglobin (Hb) electrophoresis, serum ferritin and high resolution ultrasound for the measurement of carotid artery intima media thickness (CIMT) were done. Serum triglycerides, total cholesterol, apoprotein A (ApoA), and CIMT were significantly elevated, while high density lipoproteins (HDL) were significantly lowered in thalassemic and diabetic patients compared to controls. In thalassemic patients, CIMT was positively correlated with age, Hb F, ferritin and cholesterol levels. Atherogenic lipid profiles in young thalassemic patients with increased CIMT highlights their importance as prognostic factors for vascular risk stratification.