Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome.

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression.

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling and functional studies demonstrate that lactate dehydrogenase A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer and activator of transcription 3 (STAT3) transcriptional co-activators in glioblastoma cells to upregulate C-C motif chemokine ligand 2 (CCL2) and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

Epigenetic regulation of tumor-immune symbiosis in glioma.

Glioma is a type of aggressive and incurable brain tumor. Patients with glioma are highly resistant to all types of therapies, including immunotherapies. Epigenetic reprogramming is a key molecular hallmark in tumors across cancer types, including glioma. Mounting evidence highlights a pivotal role of epigenetic regulation in shaping tumor biology and therapeutic responses through mechanisms involving both glioma cells and immune cells, as well as their symbiotic interactions in the tumor microenvironment (TME). In this review, we discuss the molecular mechanisms of epigenetic regulation that impacts glioma cell biology and tumor immunity in both a cell-autonomous and non-cell-autonomous manner. Moreover, we provide an overview of potential therapeutic approaches that can disrupt epigenetic-regulated tumor-immune symbiosis in the glioma TME.

Psychosocial and mental profile of children with sickle cell disease and their caregivers.

Sickle cell disease (SCD), a chronic debilitating disorder that may negatively affect health-related quality-of-life (HRQoL). In this observational, case-control study, we aim to assess the prevalence of impaired psychosocial profile and poor HRQoL among SCD patients and their caregivers as well as to determine the association of such impairment with parameters of disease severity. Sixty-five children and adolescents with SCD and 65 age- and sex-matched healthy controls and their caregivers were recruited. Demographic and clinical characteristics were collected, and a thorough clinical and psychiatric assessments and HR QoL were conducted. Recruited children and adolescents with SCD were 34 (52.3%) boys and 31 (47.7%) girls, and their mean age was 11.40 ± 3.55. Most of them (n = 44, 67.7%) had sickle HbSß+, and vaso-occlusive crises were the most common causes for hospital admission (n = 24, 36.9%). Children with SCD and their caregivers had depression and anxiety symptoms scores higher than reported in the control group. Children with SCD had significantly less self-esteem and less QoL scores with the least scores were in the communication domain. This adverse psychological profile was significantly negatively correlated with the age of the child, duration of illness, number and duration of hospitalizations, disease severity score, and occurrence of complications. We conclude that HRQoL of children suffering from SCD, and their caregivers are adversely affected necessitating implementation of interventions which focus on reducing depressive symptoms, enhancing self-esteem and QoL.

Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.

Glioblastoma (GBM) is a hypoxic and "immune-cold" tumor containing rich stromal signaling molecules and cell populations, such as proteases and immunosuppressive tumor-associated macrophages (TAMs). Here, we seek to profile and characterize the potential proteases that may contribute to GBM immunosuppression. Legumain (LGMN) emerges as the key protease that is highly enriched in TAMs and transcriptionally upregulated by hypoxia-inducible factor 1-alpha (HIF1α). Functionally, the increased LGMN promotes TAM immunosuppressive polarization via activating the GSK-3ß-STAT3 signaling pathway. Inhibition of macrophage HIF1α and LGMN reduces TAM immunosuppressive polarization, impairs tumor progression, enhances CD8+ T cell-mediated anti-tumor immunity, and synergizes with anti-PD1 therapy in GBM mouse models. Thus, LGMN is a key molecular switch connecting two GBM hallmarks of hypoxia and immunosuppression, providing an actionable therapeutic intervention for this deadly disease.

LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression.

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase (LDH) inhibitor stiripentol (an FDA-approved anti-seizure drug for Dravet Syndrome) emerges as the top hit. Combined profiling and functional studies demonstrate that LDHA-directed ERK pathway activates YAP1/STAT3 transcriptional co-activators in glioblastoma cells to upregulate CCL2 and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

Effect of fetuin-A on adenine-induced chronic kidney disease model in male rats.

Objectives: This study aimed to investigate the possible effects of fetuin-A on an adenine-induced chronic kidney disease (CKD) model in male rats. Materials and Methods: Rats were divided into three groups: group A included rats fed a normal diet; group B included rats fed a normal diet with 220 mg/kg adenine daily for 21 days; group C included rats fed a normal diet with 220 mg/kg adenine daily for 21 days and intraperitoneally administered with 5 mg\kg fetuin-A every other day for 2 weeks. Serum samples were assayed for serum creatinine, urea, sodium, potassium, calcium, phosphorus, tumor necrosis factor (TNF), interleukin-6 (IL-6), and estimated glomerular filtration rate (eGFR), and immunohistochemical staining was performed. Results: Group B showed a significant increase in serum creatinine, urea, phosphorus, potassium, TNF, and IL-6 and a significant decrease in serum sodium, calcium, and eGFR compared with group A. Regarding immunohistochemistry, group B showed increased apoptosis. In group C, fetuin-A reduced the urea, creatinine, and phosphorus levels, and in group C, fetuin-A decreased inflammation and apoptosis by reduction of caspase-3 staining. Conclusion: Fetuin-A improved kidney function in CKD due to its anti-inflammatory and anti-fibrotic role.

BCL11A Polymorphism in Egyptian Children with ß-Thalassemia: Relation to Phenotypic Heterogeneity.

Fetal hemoglobin (HbF) is a potent genetic modifier of ß-thalassemia phenotype. B-cell lymphoma 11A ( BCL11A ) gene results in significant silencing of HbF. The aim of this study was to assess the prevalence of different BCL11A genotypes among a cohort of Egyptian children with ß-thalassemia and to correlate them to HbF and clinical severity score. Eighty-two children with ß-thalassemia (aged 12.95 ± 3.63 years) were recruited from the Pediatric Hematology Clinic, Ain Shams University. They were divided based on the clinical severity of ß-thalassemia into three subgroups: 20 mild (24.4%), 24 moderate (29.3%), and 38 severe (46.3%). Age, gender, age of diagnosis, initial HbF level, transfusion history, and history of splenectomy were assessed. Anthropometric measures, signs of anemia and hemosiderosis, and the severity score were determined. Laboratory investigations such as complete blood picture, ferritin, and single gene polymorphism genotyping of the rs11886868 were also performed. Our findings showed that 16 children had CC genotype (19.5%), 38 had TC genotype (46.3%), and 28 had TT genotype (34.1%) of the rs#. ß-thalassemia children with TT genotype had significantly higher severity scoring than the other two groups ( p < 0.001). Moreover, mean initial HbF was found to be lower in children with TT genotype followed by TC and CC genotypes ( p < 0.001). Increased γ-globin expression associated with BCL11A gene polymorphism is associated with better clinical severity of ß-thalassemia.

Sputum neutrophil elastase and its relation to pediatric bronchiectasis severity: A cross-sectional study.

Background and Aims: Sputum neutrophil elastase (NE) is a marker of neutrophilic airway inflammation in bronchiectasis. Yet, not much is known about its role in pediatric bronchiectasis severity. This study aimed to assess the sputum NE value as a biomarker of clinical and radiological severity in pediatric bronchiectasis. Methods: This was a cross-sectional study assessing sputum NE in a total of 50 bronchiectasis patients under the age of 18 years-30 patients with cystic fibrosis (CF) and 20 patients with non-CF bronchiectasis were included. Bronchiectasis severity was assessed using Shwachman-Kulczycki (SK) score, CF-ABLE score, and CF risk of disease progression score, among CF patients, and bronchiectasis severity index (BSI) and FACED criteria among non-CF bronchiectasis patients, associations between sputum NE and bronchiectasis severity were assessed in both patient groups. Results: Sputum NE was directly correlated with C-reactive protein (r = 0.914, p < 0.001), (r = 0.786, p < 0.001), frequency of exacerbations (r = 0.852, p < 0.001) (r = 0.858, p < 0.001), exacerbations severity (r = 0.735, p = 0.002), (r = 0.907, p < 0.001), and the number of hospital admissions (r = 0.813, p < 0.001), (r = 0.612, p =0.004) in the last year among CF, and non-CF bronchiectasis patients, respectively. Additional linear correlations were found between sputum NE, CF risk of disease progression score (p < 0.001), CF-ABLE score (p < 0.001), and lower forced expiratory volume 1% of predicted (p = 0.017; ρ = -0.8) among CF patients. Moreover, sputum NE was positively correlated with the neutrophil count (p = 0.018), and BSI severity score (p = 0.039; ρ = 0.465) among non-CF bronchiectasis patients. Conclusions: Sputum NE may be considered a good biomarker of bronchiectasis severity in both CF and non-CF bronchiectasis patients, as confirmed by the exacerbations rate, CF risk of disease progression, and BSI scores.

Seasonal Variation of Presentation of Perforated Peptic Ulcer Disease: An Overview of Patient Demographics, Management and Outcomes.

Background Perforated peptic ulcer disease (PUD) is one of the most common causes of acute peritonitis. It carries significant mortality and morbidity. Several previous studies have reported a seasonal variation in the presentation of patients with perforated ulcers. Here we present this study from our experience in a Northern Irish acute district hospital. Methods A retrospective cohort study was conducted on perforated peptic ulcer patients who presented to Altnagelvin Area Hospital emergency department between 2015 to 2020. Data on patient demographics, clinical presentation, investigations, management and outcomes were collected. Primary outcome was to investigate if seasonality was associated with the incidence of perforated peptic ulcers. Follow-up data were also collected. Seasons were defined as per UK Met Office. Results A total of 50 patients presented with perforated PUD. Male to female ratio was approximately 3:2. Peaks were noted in spring and winter. April was the most common month for presentation followed by December. Smoking was the most common risk factor followed by alcohol abuse. Fourteen patients (28%) were either very frail or had contained perforations and were conservatively managed. Three deaths were noted (6%). Thirteen patients (26%) required ICU admission at some stage in their management. Conclusion Slight seasonal variation was noted in the presentation of perforated peptic ulcers in our study with a higher incidence in the winter and spring months. The month of April was noted to have the peak incidence of the disease in our study.

Acute Pancreatitis During COVID-19 Pandemic: An Overview of Patient Demographics, Disease Severity, Management and Outcomes in an Acute District Hospital in Northern Ireland.

Background Acute pancreatitis (AP) is a common disease requiring admissions under surgical and critical care units. The two most common causes are alcohol and gallstones. Coronavirus disease 2019 (COVID-19) pandemic had a significant impact on service delivery and patient management throughout all surgical specialties. In this study, the primary aim was to ascertain the incidence of COVID-19 in acute pancreatitis patients. Secondary objectives were to study aetiology, demographics, severity, 30-day mortality, outcomes and management of acute pancreatitis patients from 1st March, 2020 till 31st August, 2020. Methods A retrospective observational review of all patients admitted under the General Surgical team was performed. Information regarding demographics, severity of AP (using Glasgow score, Atlanta classification and CT severity index score), ICU admission and organ support, treatment modalities and follow-up data for outcomes was collected based on data collection tool used by COVID-PAN study and results were compared to outcomes results of COVID-PAN study. Results Forty-three (43) patients were admitted with AP. Only one patient (2.3%) was diagnosed with COVID-19 at the time of pancreatitis. Gallstones were noted to be the most common cause of AP in our population. Mortality was 7% (3 patients). Five patients (11%) needed ITU admission due to organ dysfunction. Three patients (7%) developed ARDS. Conclusion The overall incidence of COVID-19 in pancreatitis in our population of the study was low. The incidence of COVID-19 during the first wave in Derry/Londonderry area was low and this may explain why the incidence was low in our study as well. Patients with AP in our target population were mostly elderly, one in five had moderate to severe or severe pancreatitis and in 16.3% the aetiology could not be identified. As observed in other centres globally, urgent cholecystectomy for gallstone pancreatitis faced significant delays with no patients being offered index cholecystectomy and only 4 out of 19 patients having undergone interval cholecystectomy within six months of index admission for gallstone pancreatitis in our centre.

Treatment outcomes for childhood acute lymphoblastic leukemia in low-middle income country before minimal residual disease risk stratification.

BACKGROUND: Outcome of childhood acute lymphoblastic leukemia (ALL) in low- and middle-income countries is lagging in many aspects including diagnosis, risk stratification, access to treatment and supportive care. OBJECTIVE: to report the outcome of childhood ALL at Ain Shams University Children's Hospitals with the use of risk-based protocols before the implementation of minimal residual disease technology and to evaluate the use of double delayed intensification (DDI) in standard risk patients. METHODS: Two hundred and twenty patients with ALL diagnosed between January 2005 and December 2014 were included in the study. Patients were treated according to a modified CCG 1991 and 1961 for standard and high risk respectively. Patients were stratified into three risk groups: standard risk (SR), high-risk standard arm (HR-SA), and high-risk augmented arm (HR-AA). RESULTS: Among the whole cohort, the 10-year event-free survival (EFS) and overall survival (OS) were 78.1% and 84.3% respectively. Patients with Pre-B immunophenotype (IPT) had significantly better outcome than T-cell IPT (EFS 82.0% versus 58.6%, p < 0.001; OS 86.9% versus 69%, p = 0.003 for Pre-B and T-cell respectively). Among the SR group, patients treated with single delayed intensification (SDI) had comparable EFS and OS rates when compared to patients treated with DDI with EFS 82.4% versus 87.5%, p = 0.825 and OS 88.2% versus 93.5%, p = 0.638 for SDI and DDI groups, respectively. CONCLUSION: The use of risk-based protocol with simple laboratory techniques resulted in acceptable survival outcome in resource limited settings. The use of double delayed intensification showed no survival advantage in patients with standard risk.

Renal Cell Carcinoma Metastasis to the Breast: A Rare Presentation.

Worldwide breast malignancy is the most common cancer in women; however, metastases to the breast from extramammary malignancies are very rare and only a few sporadic cases are reported in the international literature. In this article, the authors report a case of a 73-year-old woman, who underwent nephrectomy for clear cell renal cell carcinoma and 3 years later presented with a breast metastasis from renal cell carcinoma (clear cell type).

Therapeutic Assessment of Combination Therapy with a Neprilysin Inhibitor and Angiotensin Type 1 Receptor Antagonist on Angiotensin II-Induced Atherosclerosis, Abdominal Aortic Aneurysms, and Hypertension.

Combined neprilysin (NEP) inhibition (sacubitril) and angiotensin type 1 receptor (AT1R) antagonism (valsartan) is used in the treatment of congestive heart failure and is gaining interest for other angiotensin II (AngII)-related cardiovascular diseases. In addition to heart failure, AngII promotes hypertension, atherosclerosis, and abdominal aortic aneurysms (AAAs). Similarly, NEP substrates or products have broad effects on the cardiovascular system. In this study, we examined NEP inhibition (with sacubitril) and AT1R antagonism (with valsartan) alone or in combination on AngII-induced hypertension, atherosclerosis, or AAAs in male low-density lipoprotein receptor-deficient mice. Preliminary studies assessed drug delivery via osmotic minipumps for simultaneous release of sacubitril and/or valsartan with AngII over 28 days. Mice were infused with AngII (1000 ng/kg per minute) in the absence (vehicle) or presence of sacubitril (1, 6, or 9 mg/kg per day), valsartan (0.3, 0.5, 1, 6, or 20 mg/kg per day), or the combination thereof (1 and 0.3, or 9 or 0.5 mg/kg per day of sacubitril and valsartan, respectively). Plasma AngII and renin concentrations increased 4-fold at higher valsartan doses, indicative of removal of AngII negative feedback on renin. Sacubitril doubled plasma AngII concentrations at lower doses (1 mg/kg per day). Valsartan dose-dependently decreased systolic blood pressure, aortic atherosclerosis, and AAAs of AngII-infused mice, whereas sacubitril had no effect on atherosclerosis or AAAs but reduced blood pressure of AngII-infused mice. Combination therapy with sacubitril and valsartan did not provide additive benefits. These results suggest limited effects of combination therapy with NEP inhibition and AT1R antagonism against AngII-induced hypertension, atherosclerosis, or AAAs. SIGNIFICANCE STATEMENT: The combination of valsartan (angiotensin type 1 receptor antagonist) and sacubitril (neprilysin inhibitor) did not provide benefit above valsartan alone on AngII-induced hypertension, atherosclerosis, or abdominal aortic aneurysms in low-density lipoprotein receptor-deficient male mice. These results do not support this drug combination in therapy of these AngII-induced cardiovascular diseases.

Multiple Myeloma Breast Involvement: A Case Report.

Multiple Myeloma involving the breast is very rare and the diagnosis is challenging because the clinical and radiological features of breast multiple myeloma are indistinguishable to other forms of breast disease whether primary or metastatic. In this article the authors report a case presented with breast masses, which were found to be extra osseous Multiple Myeloma. The patient was managed for multiple spinal lesions that were primarily thought to be metastasis from primary breast cancer.

Laparoscopic Ventral Hernia Repair Combined with Sleeve Gastrectomy in Morbidly Obese Patients: Early Outcomes.

Background Morbid obesity is a serious chronic condition with, among other symptoms, increased intra-abdominal pressure and subsequent abdominal wall hernias. The optimal management of these manifestations is still controversial. The objective of this study was to assess the early postoperative outcomes of a surgical approach combining laparoscopic ventral hernia repair (LVHR) with sleeve gastrectomy in morbidly obese patients. Methods In this retrospective study, we reviewed the files of patients who are obese with a primary ventral hernia of less than 10 cm in diameter who received simultaneous laparoscopic sleeve gastrectomy and LVHR at our institution between February 2016 and July 2018. LVHR was performed using an intraperitoneal only mesh. The individual mesh size was chosen based on the number and size of the defects. Clinical and radiological follow-ups were performed between 9 and 15 months. Results A total of 15 patients were included. Five of them were males. The mean body mass index was 45.2 kg/m 2 (range: 38.7-56.2 kg/m 2 ). The mean hernia defect size was 2.6 cm (range: 1.3-4.2 cm). Mesh size was 10 × 15 cm in five, 20 × 15 cm in seven, and 25 cm× 20 cm in three patients. All patients were discharged without complications on the second postoperative day. Mean follow-up was at 12 months. One patient presented with hernia recurrence 14 months after surgery and four patients presented with self-limited seroma. Conclusion Despite ambiguous guidelines and ongoing debate regarding simultaneous bariatric surgery and ventral hernia repair, the short-term outcomes of this approach appeared promising, provided that patients are carefully selected and receive an individually tailored approach.

Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim.

Congenital amegakaryocytic thrombocytopenia (CAMT) is an inherited disorder characterized at birth by thrombocytopenia with reduced megakaryocytes, which evolves into generalized bone marrow aplasia during childhood. Although CAMT is genetically heterogeneous, mutations of MPL, the gene encoding for the receptor of thrombopoietin (THPO), are the only known disease-causing alterations. We identified a family with three children affected with CAMT caused by a homozygous mutation (p.R119C) of the THPO gene. Functional studies showed that p.R119C affects not only ability of the cytokine to stimulate MPL but also its release, which is consistent with the relatively low serum THPO levels measured in patients. In all the three affected children, treatment with the THPO-mimetic romiplostim induced trilineage hematological responses, remission of bleeding and infections, and transfusion independence, which were maintained after up to 6.5 years of observation. Recognizing patients with THPO mutations among those with juvenile bone marrow failure is essential to provide them with appropriate substitutive therapy and prevent the use of invasive and unnecessary treatments, such as hematopoietic stem cell transplantation or immunosuppression.

Efficacy of different modes of fractional CO2 laser in the treatment of primary cutaneous amyloidosis: A randomized clinical trial.

BACKGROUND: Primary cutaneous amyloidosis (PCA) comprises three main forms: macular, lichen, and nodular amyloidosis. The current available treatments are quite disappointing. OBJECTIVES: Assess and compare the clinical and histological changes induced by different modes of Fractional CO2 laser in treatment of PCA. PATIENTS AND METHODS: Twenty five patients with PCA (16 macular and 9 lichen amyloidosis) were treated by fractional CO2 using; superficial ablation (area A) and deep rejuvenation (area B). Each patient received 4 sessions with 4 weeks intervals. Skin biopsies were obtained from all patients at baseline and one month after the last session. Patients were assessed clinically and histologically (Congo red staining, polarized light). Patients were followed-up for 3 months after treatment. RESULTS: Both modes yielded significant reduction of pigmentation, thickness, itching, and amyloid deposits (P-value < 0.001). However, the percentage of reduction of pigmentation was significantly higher in area A (P-value = 0.003). Pain was significantly higher in area B. Significant reduction in dermal amyloid deposits denotes their trans-epidermal elimination induced by fractional photothermolysis. CONCLUSION: Both superficial and deep modes of fractional CO2 laser showed comparable efficacy in treatment of PCA. Superficial mode being better tolerated by patients, is recommended as a valid therapeutic option.

Morbidities and mortality in transfusion-dependent Beta-thalassemia patients (single-center experience).

BACKGROUND: The improvement of quality and duration of life of transfusion-dependent B thalassemia patients over the last years discloses several complications due to the underling disorder, iron overload and the treatment with iron chelators. Our Aim was to assess the morbidity patterns and mortality rate of transfusion-dependent thalassemia patients, and compare the outcomes in relation to age of onset, type, duration, and compliance to iron chelation therapy and frequency of blood transfusion. PROCEDURE: This retrospective study included 447 transfusion-dependent ß-thalassemia patients who attended the Thalassemia Center, Ain Shams University Children's Hospital over the last 10 years in the period between January 2000 and January 2010. Data were collected from the patients or their caregivers, as well as by reviewing follow up sheets for examinations and investigations done to detect morbidities as well as iron chelation therapies given. Determination of mortality rate and the causes of death were also done. RESULTS: Results revealed that the most common morbidities were endocrinologic (44.7%) followed by cardiovascular (41.3%) and hepatic (40.5%), then renal (4%). The different iron chelation therapy groups showed a comparable prevalence of different morbidities. The mortality rate was 1.5% and infection was the most common cause of death. The 5, 10, 20 years' survival rate among the studied patients was 80%, 50%, 20%, respectively. CONCLUSION: In the past 10 years, the survival and morbidity rates in our center have markedly improved as a result of regular blood transfusion, new iron chelators, and better compliance of the patients.