Publications by authors named "Yasser Wali"

92 Publications

Omani experience with the use of factor IX Fc fusion protein.

BMJ Case Rep 2021 Jul 21;14(7). Epub 2021 Jul 21.

Department of Child Health, Sultan Qaboos University, Muscat, Oman.

We describe our local experience in the management of haemophilia B patients with factor IX Fc fusion protein. Two children with haemophilia B were managed with the use of a personalised/tailored dosing schedule of factor IX Fc fusion protein. Compared with the standard half-life factor IX, prophylaxis with factor IX Fc fusion protein was cost-effective, with much less injections, better bleeding control, improved tolerability or no inhibitor development.
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http://dx.doi.org/10.1136/bcr-2020-241154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296795PMC
July 2021

Rare inherited coagulation disorders in young children in Oman.

Pediatr Hematol Oncol 2021 May 20:1-21. Epub 2021 May 20.

Pediatric Hematology Oncology Unit, Department of Child Health, Sultan Qaboos University Hospital, Oman.

Background: Rare coagulation disorders represent 3-5% of all inherited coagulation deficiencies and are usually inherited as autosomal recessive. Oman has high rate of consanguineous marriages; we aimed to study the prevalence, presentation and management in affected Omani children. Retrospective study in pediatric patients with rare coagulation disorders in a tertiary hospital in Oman from 2009 to 2020. Rare coagulation disorders were diagnosed in 79 patients (39 males/40 females), aged 1 day to 13 years, accounting for 24.7% (79/319) of all children with inherited coagulation disorders; remainder included patients with hemophilia and von Willebrand disease. FXI deficiency was most common with prevalence of 39.2%, followed by fibrinogen disorders 32.9%, FVII 18.9%, FV 5%, FXIII 2.5%, and FX deficiencies 1.2%. Manifestations ranged from mild to serious to rare/atypical; presentation at birth, ruptured-hemorrhagic ovarian cyst, splenic laceration-rupture, and sight-threatening retrobulbar-intraocular hemorrhage. Intracranial hemorrhage (ICH) occurred in 9/79 patients, it was initial mode of presentation in seven of them. Global developmental delay as a complication occurred in three. Standardized treatment strategies were used with prophylaxis initiation early in life in severely affected children. This ethnic group demonstrated unique features in terms of: heterogenous/atypical presentations; severe manifestations in moderate phenotype hypofibrinogenemia; clinical severity and laboratory phenotype correlation in FV deficiency; poor association between factor activity level and bleeding severity in FVII deficiency and severe bleeding tendency despite moderate laboratory phenotype in FXIII deficiency. We recommend multicenter collaboration to identify the genotype-phenotype correlation and therapeutic options of such rare, yet serious disorders.
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http://dx.doi.org/10.1080/08880018.2021.1928801DOI Listing
May 2021

Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet Haematol 2021 May;8(5):e334-e343

Modus Therapeutics, Stockholm, Sweden.

Background: There are no approved treatments for vaso-occlusive crises in sickle cell disease. Sevuparin is a novel non-anticoagulant low molecular weight heparinoid, with anti-adhesive properties. In this study, we tested whether sevuparin could shorten vaso-occlusive crisis duration in hospitalised patients with sickle cell disease.

Methods: We did a multicentre, double-blinded, placebo-controlled, phase 2 study in 16 public access clinical hospitals in the Netherlands, Lebanon, Turkey, Bahrain, Oman, Saudi Arabia, and Jamaica. Patients aged 12-50 years with a diagnosis of sickle cell disease (types HbSS, HbSC, HbSβ-thalassaemia, or HbSβ-thalassaemia) on a stable dose of hydroxyurea, hospitalised with vaso-occlusive crisis for parenteral opioid analgesia with a projected stay of more than 48 h were included in the study. Patients were randomly assigned (1:1) using a computer-generated randomisation scheme to receive sevuparin (18 mg/kg per day) or placebo (NaCl, 0·9% solution) intravenously for 2-7 days until vaso-occlusive crisis resolution. All individuals involved in the trial were masked to treatment allocation. The analysis was done in the intention-to-treat population. The primary endpoint was time to vaso-occlusive crisis resolution defined as freedom from parenteral opioid use (in preceding 6-10 h); and readiness for discharge as judged by the patient or physician. The trial is registered with ClinicalTrials.gov, NCT02515838.

Findings: Between Oct 7, 2015, and Feb 10, 2019, 144 patients were randomly assigned and administered sevuparin (n=69) or placebo (n=75). The median age was 22·2 years (range 12·2-33·6), 104 (72%) 144 were adults (18 years or older), and 90 (63%) were male and 54 (37%) were female. The intention-to-treat analysis for the primary endpoint showed no significant difference in median time to vaso-occlusive crisis resolution between the sevuparin and placebo groups (100·4 h [95% CI 85·5-116·8]) vs 86·4 h [70·6-95·1]; hazard ratio 0·89 [0·6-1·3]; p=0·55). Serious adverse events occurred in 16 (22%) of 68 patients in the sevuparin group and in 21 (22%) of patients in the placebo group. The most frequent treatment-emergent adverse events were pyrexia (17 [25%] in the sevuparin group vs 17 [22%] in the placebo group), constipation (12 [18%] vs 17 [22%]), and decreased haemoglobin (18 [26%] vs 9 [12%]). There were no deaths in the sevuparin group and there was one (1%) death in the placebo group after a hyper-haemolytic episode due to alloimmunisation.

Interpretation: This result, as well as the results seen in other clinical studies of inhibitors of adhesion in sickle cell disease, suggest that selectin-mediated adhesion might be important in the initiation, but not maintenance of vaso-occlusion, indicating that strategies to treat vaso-occlusive crises differ from strategies to prevent this complication.

Funding: Modus Therapeutics.
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http://dx.doi.org/10.1016/S2352-3026(21)00053-3DOI Listing
May 2021

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

JAMA 2021 04;325(15):1513-1523

University of Iowa Children's Hospital, Iowa City.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea.

Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes.

Design, Setting, And Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-β0 thalassemia, or S-β+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included.

Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194).

Main Outcomes And Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup.

Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%).

Conclusions And Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes.

Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.
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http://dx.doi.org/10.1001/jama.2021.3414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058640PMC
April 2021

COVID-19 in Omani Children with Hemato-Oncology Diseases.

Mediterr J Hematol Infect Dis 2020 1;12(1):e2020074. Epub 2020 Nov 1.

Haematology-oncology unit, Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman.

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http://dx.doi.org/10.4084/MJHID.2020.074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643782PMC
November 2020

COVID-19 in Children With Cancers and Post-Hematopoietic Stem Cell Transplantation in Oman.

J Pediatr Hematol Oncol 2021 07;43(5):e741-e742

Haematology-Oncology Unit Child Health Department Sultan Qaboos University Hospital Muscat, Oman.

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http://dx.doi.org/10.1097/MPH.0000000000001978DOI Listing
July 2021

Outcome of Early Hemostatic Intervention in Children With Sepsis and Nonovert Disseminated Intravascular Coagulation Admitted to PICU: A Randomized Controlled Trial.

Pediatr Crit Care Med 2021 03;22(3):e168-e177

Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Objectives: Evaluation of the outcome of early hemostatic management of disseminated intravascular coagulopathy in patients with severe sepsis/septic shock admitted to PICU, before the development of clinically overt disseminated intravascular coagulopathy.

Design: Prospective interventional, open label randomized controlled clinical trial.

Setting: PICU at Alexandria University Children's Hospital.

Patients: The study included 80 patients with proven severe sepsis/septic shock in nonovert disseminated intravascular coagulopathy stage. They were randomly assigned into two groups (group 1 and group 2).

Interventions: Specific intervention was applied for group 1 (plasma transfusion, low-dose unfractionated heparin, and tranexamic acid).

Measurements: All patients had assessment of Pediatric Index of Mortality 2 score, Pediatric Logistic Organ Dysfunction score, inotropic score, routine laboratory, and hemostatic tests including fibrin degradation products and d-dimers. Disseminated intravascular coagulopathy risk assessment scores were calculated on daily basis.

Results: Mortality rate was significantly higher in group 2. Progression to overt disseminated intravascular coagulopathy was significantly more common among group 2 patients than group 1 (45% and 10%, respectively) (p < 0.0001). Disseminated intravascular coagulopathyRisk Assessment Scores were significantly higher on the second and fifth days among group 2 patients. The initial specific hemostatic intervention was the only significant predictor of survival and prevention of progression to overt disseminated intravascular coagulopathy.

Conclusions: Our results suggest that early use of a combination of fresh frozen plasma transfusion, low-dose heparin, and tranexamic acid in children with severe sepsis/septic shock in the "window of opportunity" before the development of overt disseminated intravascular coagulopathy stage was associated with better outcome for survival and prevention of progression to overt disseminated intravascular coagulopathy, with no increase in bleeding risk. Larger multicenter studies are needed to further prove this practice.
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http://dx.doi.org/10.1097/PCC.0000000000002578DOI Listing
March 2021

A comprehensive update of ICET-A Network on COVID-19 in thalassemias: what we know and where we stand.

Acta Biomed 2020 09 7;91(3):e2020026. Epub 2020 Sep 7.

Pediatric Hematology Department, Çukurova University, Adana, Turkey.

A review of the literature on COVID-19 pandemic in patients with thalassemias is presented. Globally, the prevalence of COVID-19 among  β-thalassemia patients seems to be lower than in general population; associated co-morbidities aggravated the severity of  COVID- 19, leading to a poorer prognosis, irrespective of age. A multicenter registry will enhance the understanding of COVID-19 in these patients and will lead to more evidence-based management recommendations.
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http://dx.doi.org/10.23750/abm.v91i3.10063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716954PMC
September 2020

Preliminary Data on COVID-19 in Patients with Hemoglobinopathies: A Multicentre ICET-A Study.

Mediterr J Hematol Infect Dis 2020 1;12(1):e2020046. Epub 2020 Jul 1.

Center of Thalassemia, Baku, Azerbaijan.

Objectives: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent β thalassemia major (TM), β-thalassemia intermedia (TI) and sickle cell disease (SCD).

Design: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey.

Main Outcome Data: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized.

Results: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl).

Conclusions: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID- 19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age.
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http://dx.doi.org/10.4084/MJHID.2020.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340245PMC
July 2020

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

Cancer 2020 09 10;126(18):4235-4245. Epub 2020 Jul 10.

Department of Pediatrics, Al Bairouni Hospital, Damascus, Syria.

Background: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated.

Methods: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database.

Results: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey.

Conclusions: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.
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http://dx.doi.org/10.1002/cncr.33075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404449PMC
September 2020

Sepsis-related anemia in a pediatric intensive care unit: transfusion-associated outcomes.

Transfusion 2020 02;60 Suppl 1:S4-S9

Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Background: Pediatric patients with sepsis in intensive care units are at high risk of developing anemia, which might have adverse effects on their prognosis. This study aimed to evaluate the impact of red blood cell (RBC) transfusion on the outcomes of patients admitted to a pediatric intensive care unit (PICU) with sepsis.

Methods: We conducted a prospective randomized clinical trial, enrolling 67 children, aged 2 to 144 months who were admitted to a PICU with a new episode of sepsis from November 2017 to April 2018. Patients were allocated randomly to two groups: Group 1, liberal transfusion strategy group, including 33 patients who had initial hemoglobin (Hb) between 7 or greater and less than 10 g/dL and received an RBC top-up transfusion to 12 g/dL; and Group 2, restrictive strategy group, including 34 patients who had the same Hb range and did not receive RBCs. Patients with Hb less than 7 or greater than 10 g/dL were excluded.

Results: Of 33 patients who received liberal transfusions, 31 (93.94%) required ventilation, and 29 (87.88%) had multiorgan dysfunction. They had a significantly lengthier hospital stay and a higher incidence of acute respiratory distress syndrome and acute lung injury. Moreover, mortality was significantly higher in the liberal transfusion group (42.4% vs. 17.6%).

Conclusions: Compared to the restrictive transfusion strategy, liberal transfusion might be associated with a worse outcome. However, the possible role of other known and unknown confounding factors and minor protocol violations should be taken into consideration. We recommend minimizing factors worsening anemia in PICU patients to reduce the need for transfusion.
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http://dx.doi.org/10.1111/trf.15688DOI Listing
February 2020

Preoperative transfusion versus no transfusion policy in sickle cell disease patients: a randomized trial.

Transfusion 2020 02;60 Suppl 1:S22-S27

Department of Child Health, Pediatric Hematology/Oncology Unit, Sultan Qaboos University Hospital, Muscat, Oman.

Background: Many children with sickle cell disease (SCD) indicated for adenotonsillectomy receive pre-operative transfusion therapy, either simple or exchange transfusion, in order to reduce surgical and sickle cell disease-related complications.

Subjects And Methods: This is a prospective randomized controlled clinical trial aiming to compare between preoperative simple transfusion and no transfusion in pediatric patients with sickle SCD admitted in Sultan Qaboos University Hospital, Muscat, Oman for adenotonsillectomy during the period from January 2014 through June 2018. They were randomly assigned into two arms (simple transfusion and no transfusion).

Results: Postoperative SCD-related complications have been encountered in 6 out of 138 patients (4.3%). There was no statistically significant difference between the two studied groups as regards the development of surgical or SCD-related complications (p = 0.6 and 0.8 respectively). The length of postoperative hospital stay was comparable in the two groups. (p = 0.607). SCD-related complications occurred exclusively in cases with homozygous sickle anemia (4 out of 81 = 4.9%).

Conclusion: Sickle cell disease patients with a hemoglobin level above 7.5 g/dL do not need PRBCs transfusion prior to adenotonsillectomy. This approach did not increase the risk of postoperative surgical or SCD-related complications.
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http://dx.doi.org/10.1111/trf.15684DOI Listing
February 2020

α-Globin Genotypes Associated with Hb H Disease: A Report from Oman and a Review of the Literature from the Eastern Mediterranean Region.

Hemoglobin 2020 Jan 5;44(1):20-26. Epub 2020 Feb 5.

Department of Hematology, Sultan Qaboos University Hospital, Muscat, Oman.

α-Thalassemia (α-thal) is the most common autosomal recessive hemoglobinopathy. There is a vast diversity and geographical variability in underlying genotypes in Hb H (β4) patients. Herein, we describe the genotypes found in the largest report of Omani Hb H patients. Moreover, we reviewed and summarized the literature published from the Eastern Mediterranean region. A retrospective review of all genetically confirmed Hb H disease patients diagnosed between 2007 and 2017 at Sultan Qaboos University Hospital, Muscat, Oman, was performed. Hematological parameters and clinical presentations were assessed. Both α-globin genes were screened for deletional and nondeletional mutations using a stepwise diagnostic strategy as described before. A total of 52 patients (27 females and 25 males) with a mean age of 20.6 years (range 0.23-80.0) were molecularly confirmed to carry Hb H disease. The patients had a hemoglobin (Hb) level of 9.3 g/dL (range 5.7-13.0) and mean corpuscular volume (MCV) of 58.4 fL (range 48.2-82.1). A total of eight genotype combinations were identified, with α2 polyadenylation signal mutation (polyA1) (AATAA>AATAA (αα/αα), often cited as αα/αα, being the most common (53.8%) followed by -α/- - (28.8%). Our cohort also included patients with combinations of α with other Hb variants: αα/αα with Hb S (: c.20A>T) trait ( = 2), -α/αα ( = 2) and αα (: c.56delG)/αα ( = 1). Nondeletional Hb H disease due to the α mutation is the most common in Omanis. Molecular diagnosis is necessary for accurate confirmation of the diagnosis of α-thal, determination of underlying genotypes, follow-up and counseling.
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http://dx.doi.org/10.1080/03630269.2020.1720709DOI Listing
January 2020

Distribution of sickle cell disease and assessment of risk factors based on transcranial Doppler values in the Gulf region.

Hematology 2020 Dec;25(1):55-62

Department of Medicine, College of Medicine, Qatar University, Doha, Qatar.

Stroke is a potentially fatal complication of sickle cell disease (SCD). Transcranial Doppler (TCD) is useful at identifying increased risk of stroke in children with SCD and vasospasm after subarachnoid hemorrhage. The main aim of this study was to determine the proportion of patients with SCD in the Gulf region who are at a high risk of stroke, as determined by TCD. This multicenter (Oman, Qatar, and UAE), descriptive, cross-sectional study in patients (aged 2-16 years) with SCD included a baseline visit, 1 follow-up visit for patients with conditional TCD, and 3-year retrospective data analysis for all patients. Of the 410 eligible patients (Oman, 86.5%; Qatar, 8.2%; UAE, 5.1%), most had a TCD finding (left side, 91.7%; right side, 92.0%) of normal velocity (<155 cm/s) at baseline. For 6 of 7 patients with conditional velocity (155-179 cm/s) and 1 patient with high velocity (≥180 cm/s), baseline TCD results were not confirmed at follow-up. As per bivariate linear regression, age, race, transfusion type, and transfusion frequency were significant predictors of the TCD velocities. Multivariate logistic regressions revealed that TCD velocities were significantly correlated with sex, race, and type of transfusion. No patients reported any adverse events at follow-up. No deaths occurred during the study. The study results show that far fewer patients with SCD in the Gulf have abnormal TCD findings than the internationally reported. Larger studies are needed to identify the factors underlying this observation.
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http://dx.doi.org/10.1080/16078454.2020.1714113DOI Listing
December 2020

Evaluation of endocrine complications in beta-thalassemia intermedia (β-TI): a cross-sectional multicenter study.

Endocrine 2020 07 18;69(1):220-227. Epub 2019 Dec 18.

Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy.

Background: Data on the prevalence and type of endocrine disorders in β-thalassemia intermedia (β-TI) patients are scarce. This multicenter study was designed to determine the prevalence of endocrine complications and the associated risk factors in a large group of β-TI patients.

Methods: In this cross-sectional multicenter study, 726 β-TI patients, aged 2.5-80 years, registered at 12 thalassemic centers, from nine countries, were enrolled during 2017. In a subgroup of 522 patients (mean age 30.8 ± 12.1; range: 2.5-80 years) from Qatar, Iran, Oman, Cyprus, and Jordan detailed data were available.

Results: Overall, the most prevalent complications were osteopenia/osteoporosis (22.3%), hypogonadism (10.1%), and primary hypothyroidism (5.3%). In the subgroup multivariate analysis, older age was a risk factor for osteoporosis (Odds ratio: 7.870, 95% CI: 4.729-13.099, P < 0.001), hypogonadism (Odds ratio: 6.310, 95% CI: 2.944-13.521, P < 0.001), and non-insulin-dependent diabetes mellitus (NIDDM; Odds ratio: 17.67, 95% CI: 2.217-140.968, P = 0.007). Splenectomy was a risk factor for osteoporosis (Odds ratio: 1.736, 95% CI: 1.012-2.977, P = 0.045). Hydroxyurea was identified as a "protective factor" for NIDDM (Odds ratio: 0.259, 95% CI: 0.074-0.902, P = 0.034).

Conclusions: To the best of our knowledge, this is the largest cohort of β-TI patients with endocrine disorders evaluated in extremely heterogenic thalassemic populations for age, clinical, hematological, and molecular composition. The study demonstrates that endocrine complications are less common in patients with β-TI compared with β-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in β-TI patients.
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http://dx.doi.org/10.1007/s12020-019-02159-6DOI Listing
July 2020

KMT2A-MLLT3 AML Masquerading as JMML may Disguise Fatal Leukemia.

Oman Med J 2019 Nov;34(6):553-555

Pediatric Hematology, Oncology and HSCT Unit, Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.

We present a mortality case showcasing t(9;11)-positive acute myeloid leukemia/juvenile myelomonocytic leukemia (AML/JMML) overlap to shed light on this lethal molecular subtype of AML. In this case, the flawed assumption that JMML was to blame impeded the prompt undertaking of appropriate treatment for AML in our 14-month-old patient. This article aims to scrutinize the catastrophic sequel of such an overlap in leukemia and refutes the contemporary diagnostic methods.
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http://dx.doi.org/10.5001/omj.2019.99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851066PMC
November 2019

Elevated levels of circulating invariant natural killer cell subsets are skewed toward Th2-like phenotype in children with sickle cell disease.

Clin Immunol 2020 01 11;210:108308. Epub 2019 Nov 11.

Department of Child Health, Sultan Qaboos University Hospital, College of Medicine and Health Sciences, Oman.

Invariant natural killer T (iNKT) cells are being considered as potential targets for immunotherapeutic strategies in a variety of conditions including sickle cell disease (SCD). However, relatively little is known about the fate of iNKT cell subsets in children with SCD. Herein, quantitative and qualitative analyses of circulating iNKT cell subsets were carried out in 120 children in steady state and 30 healthy controls. Children with SCD displayed significantly elevated levels of circulating iNKT cell subsets with a preferential polarization toward Th2-like cells. The known SCD modifiers did not influence levels of iNKT cell subsets, except that children carrying the Bantu haplotype exhibited elevated levels of CD4iNKT cells, and to a lesser degree CD8iNKT cells. Collectively, these findings indicate that circulating iNKT cell subsets are significantly increased in children with SCD, and highlight the existence of imbalanced production of cytokines toward Th2-like phenotype, which seems to be associated with genetic polymorphisms.
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http://dx.doi.org/10.1016/j.clim.2019.108308DOI Listing
January 2020

Pulmonary Artery Pseudoaneurysm in a Child With β-Thalassemia Major.

J Pediatr Hematol Oncol 2020 08;42(6):e503-e506

Departments of Child Health.

Pulmonary artery aneurysms and pseudoaneurysms are rare vascular anomalies in children that can lead to massive hemoptysis resulting in severe morbidity and even mortality. High level of clinical suspicion, timely diagnosis, and prompt management are important for a better outcome. Here, we report a case of a 14-year-old adolescent with β-thalassemia major who presented with life-threatening hemoptysis due to pulmonary artery pseudoaneurysm and was successfully treated with coil embolization.
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http://dx.doi.org/10.1097/MPH.0000000000001576DOI Listing
August 2020

HAEMOcare: The First International Epidemiological Study Measuring Burden of Hemophilia in Developing Countries.

TH Open 2019 Apr 27;3(2):e190-e199. Epub 2019 Jun 27.

Haemophilia Comprehensive Care Centre, Charlotte Maxeke Johannesburg Hospital, Department of Molecular Medicine and Haematology, National Health Laboratory Service and Faculty of the Health Sciences, University of Witwatersrand, Johannesburg, South Africa.

 Optimizing hemophilia care remains challenging in developing countries. Burden-of-disease studies are important to develop strategies for improving hemophilia care.  The HAEMOcare study evaluated the factors contributing to hemophilia-related orthopedic disease burden in developing countries.  HAEMOcare was a noninterventional, cross-sectional, epidemiological study conducted in Algeria, India, Morocco, Oman, and South Africa. Male patients with severe hemophilia (  = 282) aged ≥6 years, without or with inhibitors, being treated on-demand for bleeding were included. Hemophilia-related orthopedic clinical and functional status was assessed using the Hemophilia Joint Health Score (HJHS), radiological status with the Pettersson Score, and quality of life with the EuroQol five-dimension questionnaire (EQ-5D-3L). Direct and indirect economic costs of hemophilia care were also calculated.  Patients (mean [standard deviation, SD] age: 20.8 [10.6] years) experienced a mean annualized bleeding rate of 25.8. Overall mean (SD) HJHS and Pettersson score were 17.9 (12.8) and 15.0 (13.5), respectively; scores were similar between patients without or with inhibitors (  = 0.21 and 0.76, respectively). Approximately 70% of adults reported problems relating to pain/discomfort and mobility parameters in the EQ-5D-3L. Mean distance to a hemophilia treatment center (HTC) was 79.4 km. As expected, total costs of hemophilia were statistically significantly higher in patients with inhibitors versus without inhibitors (  = 0.002).  Inadequate access to HTCs and expert care, along with high bleeding rates, led to equivalent hemophilia-related orthopedic morbidity between hemophilia patients without and with inhibitors. HAEMOcare documented the economic and disease burdens associated with suboptimal hemophilia care in developing countries.
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http://dx.doi.org/10.1055/s-0039-1688414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598083PMC
April 2019

An ICET-A survey on occult and emerging endocrine complications in patients with β-thalassemia major: Conclusions and recommendations.

Acta Biomed 2019 01 15;89(4):481-489. Epub 2019 Jan 15.

Quisisana Hospital, Ferrara.

In adult thalassemia major (TM) patients, a number of occult and emerging endocrine complications, such as: central hypothyroidism (CH), thyroid cancer, latent hypocortisolism, and growth hormone deficiency (GHD) have emerged and been reported. As the early detection of these complications is essential for appropriate treatment and follow-up, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) promoted a survey on these complications in adult TM patients, among physicians (pediatricians, hematologists and endocrinologists) caring for TM patients in different countries. The data reported by 15 countries are presented.The commonest endocrine complications registered in 3.114 TM adults are CH and GHD (4.6 % and 3.0 %, respectively), followed by latent hypocortisolism (1.2%). In 13 patients (0.41%) a cytological papillary or follicular thyroid carcinoma was diagnosed in 11 and 2 patients, respectively, and a lobectomy or thyroidectomy was carried out. Of 202 TM patients below the age of 18 years, the  reported endocrine complications were: GHD in 4.5%, latent hypocortisolism in 4.4% and central hypothyrodisim in 0.5%. Transition phase was an area of interest for many clinicians, especially as patients with complex chronic health conditions are responding to new treatments extending their lifespan beyond imagination.. In conclusion, our survey provides a better understanding of  physicians' current clinical practices and beliefs in the detection, prevention and treatment of some endocrine complications prevailing in adult TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are recommended.
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http://dx.doi.org/10.23750/abm.v89i4.7774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502100PMC
January 2019

Hemoglobin F as a predictor of health-related quality of life in children with sickle cell anemia.

Qual Life Res 2019 Feb 22;28(2):473-479. Epub 2018 Oct 22.

Department of Child Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.

Purpose: As treatment options for children with sickle cell anemia (SCA) continue to expand survival, evaluation of factors associated with health-related quality of life (HRQoL) is becoming an important aspect for further improving clinical management. Although the general features of SCA are similar, factors influencing HRQoL within a country may differ from those of other countries, therefore this study aimed to explore factors affecting HRQoL in children with SCA living in the Sultanate of Oman.

Methods: This was a cross-sectional study in which the PedsQL™ Sickle Cell Disease Module was used to evaluate the overall HRQoL in children with SCA. The socio-demographic data, clinical, and treatment outcomes were collected. Univariate and multivariate linear regression analyses were used to identify predictors of HRQoL.

Results: A total of 123 children with SCA, aged from 2 to 16 years were enrolled. The mean total HRQoL score was 52 ± 15% (9-94), where Worry II scale recorded the highest score. The multiple regression analysis revealed that the only predictors of total HRQoL score were hemoglobin F (B = 0.64, 95% confidence interval [CI] 0.149-1.118, P = 0.009) and to a lesser degree white blood cell count (B = - 0.99, 95% CI - 1.761 to - 0.198, P = 0.01), independently of other study parameters such as age, gender, spleen status, and hydroxyurea therapy.

Conclusions: Collectively, these findings indicated that hemoglobin F out-weighted white blood cell count in predicting HRQoL in Omani children with SCA. Recognition of these factors could help health professionals to develop effective strategies to improve the overall HRQoL in these young patients.
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http://dx.doi.org/10.1007/s11136-018-2031-0DOI Listing
February 2019

An ICET- A survey on Hypoparathyroidism in Patients with Thalassaemia Major and Intermedia: A preliminary report.

Acta Biomed 2018 01 16;88(4):435-444. Epub 2018 Jan 16.

Quisisana Hospital, Ferrara.

Hypoparathyroidism (HPT) is a rare disease with leading symptoms of hypocalcemia, associated with high serum phosphorus levels and absent or inappropriately low levels of parathyroid hormone (PTH). In patients with thalassemias it is mainly attributed to transfusional iron overload, and suboptimal iron chelation therapy. The main objectives of this survey were to provide data on the prevalence, demographic and clinical features of HPT in thalassemia major (TM) and intermedia (TI) patients living in different countries, and to assess its impact in clinical medical practice. A questionnaire was sent to all Thalassemia Centres participating to the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) Network.Seventeen centers, treating a total of 3023 TM and 739 TI patients, participated to the study. HPT was reported in 206 (6.8%) TM patients and 33 (4.4%) TI patients. In general, ages ranged from 10.5 to 57 years for the TM group and from 20 to 54 years for the TI group. Of the 206 TM patients and 33 TI patients with HPT, 117 (48.9%) had a serum ferritin level >2.500 ng/ml (54.3% TM and 15.1% TI patients) at the last observation. Hypocalcemia varied in its clinical presentation from an asymptomatic biochemical abnormality to a life-threatening condition, requiring hospitalization. Calcium and vitamin D metabolites are currently the cornerstone of therapy in HPT. In TM patients, HPT was preceded or followed by other endocrine and non-endocrine complications. Growth retardation and hypogonadism were the most common complications (53.3% and 67.4%, respectively). Although endocrine complications were more common in patients with TM, non-transfused or infrequently transfused patients with TI suffered a similar spectrum of complications but at a lower rate than their regularly transfused counterparts.In conclusion, although a large international registry would help to better define the prevalence, comorbidities and best treatment of HPT, through the result of this survey we hope to give a clearer understanding of the burden of this disease and its unmet needs. HPT requires lifelong therapy with vitamin D or metabolites and is often associated with complications and comorbidities.Therefore, it is important for endocrinologists and other physicians, who care for these patients, to be aware of recent advances of this disorder.
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http://dx.doi.org/10.23750/abm.v88i4.6837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166174PMC
January 2018

Human Parvovirus B19 in Children with Sickle Cell Disease; Poking the Spleen.

Oman Med J 2017 Sep;32(5):425-428

Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman.

Parvovirus is a known culprit of transient red cell aplasia (TRCA) in children with sickle cell disease (SCD). Few reports have previously described the association between the virus and acute splenic sequestration crisis (ASSC) in the same patient. Here, we are shedding light on such a potentially serious combination by reporting two cases of siblings with SCD complicated with concurrent ASSC and TRCA and presenting a review of the relevant literature.
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http://dx.doi.org/10.5001/omj.2017.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632704PMC
September 2017

Pertussis and Pertussis like Illness: Pediatric Experience in Oman.

Oman Med J 2017 Sep;32(5):396-402

Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman; Department of Pediatrics, Faculty of Medicine, Alexandria University, Egypt.

Objectives: A resurgence of pertussis or whooping cough has been observed worldwide despite broad vaccination coverage. Pertussis like illness (PLI) refers to a clinical syndrome compatible with pertussis infection but lacking laboratory confirmation or an epidemiological link to a confirmed case. Our study aimed to estimate the contribution of infection and identifying predictors of its diagnosis in a cohort of children with PLI.

Methods: Demographic and clinical information were retrospectively collected from the medical records of children < 13 years old and hospitalized for PLI in two pediatric units in Oman from 1 January 2012 to 31 December 2013. The laboratory data of all cases were reviewed and confirmed cases of pertussis were identified, analyzed, and compared with non-confirmed cases.

Results: A total of 131 patients were enrolled in this study. The majority (95.4% [125/131]) were infants. Only 54.1% (71/131) of admitted children with PLI were tested for pertussis. The incidence of pertussis infection among the tested group was 16.9% (12/71) with a 95% confidence interval 8.2-25.6. Severe illness occurred in 56.4% (74/131) of patients, and six were confirmed to have pertussis. Pediatric intensive care unit admission was required for one confirmed case of pertussis and eight cases from the PLI group (three were negative for pertussis, and five were not tested). Receiver operator characteristic curve analysis revealed that a white blood cell count 23.5 × 10/L had 96.6% specificity and lymphocytes 17 × 10/L had 98.3% specificity.

Conclusions: Taking into consideration that the number tested for pertussis was limited, the incidence of pertussis was 16.9% (12 out of 71 patients). Lymphocytosis can be used as a reliable predictor for the diagnosis of pertussis especially in the absence of specific confirmatory tests or until their results are available.
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http://dx.doi.org/10.5001/omj.2017.75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632702PMC
September 2017

Premature ventricular contractions as a side effect of filgrastim in a child with B-thalassaemia.

Cardiol Young 2018 Jan 29;28(1):155-158. Epub 2017 Aug 29.

1Child Health Department,SQUH,Muscat,Oman.

Premature ventricular contractions are a rare side effect of filgrastim, reported mainly in elderly men. Here we report the case of a 9-year-old child with thalassaemia who developed frequent premature ventricular contractions after three doses of filgrastim were given for deferiprone-induced agranulocytosis. The arrhythmia resolved 3 weeks after discontinuation of filgrastim. Children treated with filgrastim should be carefully monitored for potentially serious arrhythmia.
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http://dx.doi.org/10.1017/S1047951117001585DOI Listing
January 2018

Haemoglobin Fontainebleau (HBA2: c. 64G>C) in Oman: molecular and haematological characteristics and interaction with various haemoglobinopathies.

J Clin Pathol 2018 Apr 7;71(4):303-308. Epub 2017 Aug 7.

Department of Haematology, Sultan Qaboos University Hospital, Muscat, Oman.

Objectives: To describe the laboratory features of haemoglobin Fontainebleau (Hb FB) and its interactions with various α and β globin gene mutations in the Omani population.

Methods: Over a period of 10 years, a total of 94 blood samples were suspected to have an α variant on HPLC at the Sultan Qaboos University Hospital, Muscat, Oman. Molecular testing was performed using PCR based techniques to define the variant and to analyse other interacting mutations in either α or β globin genes.

Results: Of 94 subjects, molecular analysis confirmed the Hb FB variant in 55 samples (38 non-cord and 17 cord blood). A total of 36/38 non-cord samples were heterozygous for the variant, while all 17 cord blood samples were heterozygotes. A total of 43/55 individuals had a concomitant α and/or β globin gene mutation.

Conclusions: Hb FB is the the most common α variant in the Omani population. We report the different HPLC profiles of this variant that we observed, with and without other haemoglobinopathies in non-cord and cord blood samples. This is the first report describing the HPLC profiles of this α globin chain variant on 1 year follow-up testing of cord blood samples. With careful analysis by HPLC, it is possible not only to identify Hb FB but also to predict any concomitant α and/or β globin gene mutations.
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http://dx.doi.org/10.1136/jclinpath-2017-204617DOI Listing
April 2018

The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

Br J Haematol 2017 10 12;179(2):256-265. Epub 2017 Jul 12.

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K was markedly abnormal with elevated activities of P , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca entry and Mg loss via P stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype.
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http://dx.doi.org/10.1111/bjh.14851DOI Listing
October 2017

Vincristine-induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: Frequent autonomic and more severe cranial nerve involvement.

Pediatr Blood Cancer 2017 Dec 17;64(12). Epub 2017 Jun 17.

Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman.

Background: Vincristine (VCR) induced peripheral neuropathy is a common complication in children with acute lymphoblastic leukemia (ALL).

Procedures: A retrospective data analysis over an interval of 10 years (2006-2016) of all children with ALL seen at Sultan Qaboos University Hospital was carried out. Electronic medical records of eligible patients were reviewed. Patients with clinical evidence of neuropathy and abnormal nerve conduction studies (NCSs) were included in the study.

Results: Nineteen (nine females and 10 males) out of 103 pediatric patients developed VCR-related neuropathy, and their age ranged between 2.5 and 14 years. Symptoms started after 2-11 doses of VCR. All 19 patients had documented peripheral neuropathy on NCSs. The autonomic nervous system and cranial nerves affection was relatively common in our patients; two presented with bradycardia, two patients with unexplained tachycardia, and five had abdominal pain and constipation, complicated by typhlitis in two patients. One patient developed unilateral hearing loss. Two patients developed severe life-threatening cranial nerve involvement with bilateral ptosis and recurrent laryngeal nerve involvement presented as vocal cord paralysis, hoarseness of voice, frequent chocking, and aspiration episodes.

Conclusions: Peripheral neuropathy was the commonest form of VCR-related neuropathy. Autonomic neuropathy was relatively common in our patients. Cranial neuropathy is a serious side effect of VCR that can be severe, involving multiple cranial nerves and needs prompt recognition and management. Concomitant administration of pyridoxine and pyridostigmine does not seem to protect against further neurological damage in some patients.
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http://dx.doi.org/10.1002/pbc.26677DOI Listing
December 2017
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