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Objectives: This study aimed to assess the productivity of clinical trials in the Gulf Cooperation Council (GCC) region, including Oman, Saudi Arabia, United Arab Emirates, Qatar, Bahrain and Kuwait and to address the existing research gap. Specifically, this paper aimed to estimate the number of clinical trials conducted and estimate the proportion of clinical trials conducted in the GCC countries published in peer-reviewed journals. Methods: The clinical trials registry of the US National Library of Medicine was searched for clinical trials conducted from January 2000 to October 2019. The productivity was assessed by the publication status of the trials in the registry and through the search in MEDLINE indexed journals. Results: A total of 682 trials were found from the GCC region, with an overall trend of 4.1 trials each year. However, the clinical trial productivity from the region contributes to only 0.37% of the trials globally. When comparing the raw data, Saudi Arabia showed the highest proportion, contributing 66.6% of the clinical trials from the region (P

Simple Summary Patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 are an even greater challenge for hematologists. To better clarify their outcome, we describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Overall, 343 (76.2%) patients received treatment for HM, and an overall response rate was observed in 140 (40.8%) patients after the first line of treatment. Thirty-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004). Statistical analysis showed that, together with age, severe/critical COVID-19, >= 2 comorbidities, lack of HM treatment was an independent risk factors for mortality. These observations suggest the importance of HM treatment in these patients; therefore, it should be delivered as soon as possible for patients requiring immediate therapy. Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, >= 2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.

Background and objectives: Diagnosis glucose intolerance in pregnancy is very important in preventing maternal and fetal complications. In this study, we compared hematological and biochemical characteristics of healthy pregnant women and women with gestational diabetes mellitus (GDM) to find predisposing and prognostic variables of GDM. Methods: In this study, 80 pregnant women (at 24-28 weeks of pregnancy) were divided into a GDM group and non-GDM group by performing oral glucose tolerance test using 75 g glucose according to the International Association of the Diabetes and Pregnancy Study Groups criteria. Results: The mean age of women with GDM was significantly higher than those without GDM (p=0.048). Other variables including body mass index, gestational age and daily sleep duration did not differ significantly between the two groups (P>0.05). There was a significant association between family history of diabetes and incidence of GDM (p=0.040). In addition, the C-peptide level was significantly higher in pregnant women with GDM (p=0.004). Conclusion: Considering the role of C-peptide in predicting metabolic syndrome, it is suggested to use this factor for identification of GDM patients.

BACKGROUND: Identifying the immune cells involved in coronavirus disease 2019 (COVID-19) disease progression and the predictors of poor outcomes is important to manage patients adequately. METHODS: This prospective observational cohort study enrolled 48 patients with COVID-19 hospitalized in a tertiary hospital in Oman and 53 non-hospitalized patients with confirmed mild COVID-19. RESULTS: Hospitalized patients were older (58 years vs 36 years, P < 0.001) and had more comorbid conditions such as diabetes (65% vs 21% P < 0.001). Hospitalized patients had significantly higher inflammatory markers (P < 0.001): C-reactive protein (114 vs 4 mg/l), interleukin 6 (IL-6) (33 vs 3.71 pg/ml), lactate dehydrogenase (417 vs 214 U/l), ferritin (760 vs 196 ng/ml), fibrinogen (6 vs 3 g/l), D-dimer (1.0 vs 0.3 µg/ml), disseminated intravascular coagulopathy score (2 vs 0), and neutrophil/lymphocyte ratio (4 vs 1.1) (P < 0.001). On multivariate regression analysis, statistically significant independent early predictors of intensive care unit admission or death were higher levels of IL-6 (odds ratio 1.03, P = 0.03), frequency of large inflammatory monocytes (CD14+CD16+) (odds ratio 1.117, P = 0.010), and frequency of circulating naive CD4+ T cells (CD27+CD28+CD45RA+CCR7+) (odds ratio 0.476, P = 0.03). CONCLUSION: IL-6, the frequency of large inflammatory monocytes, and the frequency of circulating naive CD4 T cells can be used as independent immunological predictors of poor outcomes in COVID-19 patients to prioritize critical care and resources.

Objectives: Critical illness in COVID-19 is attributed to an exaggerated host immune response. Since neutrophils are the major component of innate immunity, we hypothesize that the quantum of activated neutrophils in the blood may predict an adverse outcome. Design: In a retrospective study of 300 adult patients with confirmed COVID-19, we analyzed the impact of neutrophil activation (NEUT-RI), interleukin-6 (IL-6) and the established clinical risk factors of age, diabetes, obesity and hypertension on the clinical outcome. Results: Significant predictors of the need for mechanical ventilation were NEUT-RI (Odds Ratio (OR) = 1.22, P < 0.001), diabetes (OR = 2.56, P = 0.00846) and obesity (OR = 6.55, P < 0.001). For death, the significant predictors were NEUT-RI (OR = 1.14, P = 0.00432), diabetes (OR = 4.11, P = 0.00185) and age (OR = 1.04, P = 0.00896). The optimal cut-off value for NEUT-RI to predict mechanical ventilation and death was 52 fluorescence intensity units (sensitivity 44%, specificity 88%, area under the curve 0.67 and 44%, 86%, 0.64, respectively). Conclusion: This finding supports an aberrant neutrophil response in COVID-19, likely due to uncontained viral replication, tissue hypoxia and exacerbated inflammation, introduces a novel biomarker for rapid monitoring and opens new avenues for therapeutic strategies.

Background: The coronavirus disease‐2019 (COVID‐19) caused by SARS Coronavirus 2 (SARS‐CoV‐2) is a potentially lethal infection. Cancer patients, and specifically hematopoietic cell transplant (HCT) recipients are severely immunocompromised and may be at a higher risk of a complicated course with this infection. We aimed to study the COVID-19 outcomes and severity in post HCT patients. Methods: We retrospectively reviewed post-HCT patients diagnosed with COVID-19 between March 15, 2020, and December 1, 2020 at 10 transplant centers across the Middle East. Results: We identified 91 patients with confirmed SARS-CoV-2 infection across 10 transplant centers. 52 patients were post allo-HCT while the remaining 39 patients were post auto-HCT. The median time from transplant was 14.9 months. Mortality rate was 4.4%. Hospital admission rate was 53%. ICU admission rate was 14%. Mechanical ventilation rate was 10%. Oxygen supplementation rate was 18%. Time from HCT to COVID-19 > 6 months was associated with lower admission rates and lower rates of the “severity” composite endpoint. Antibody responses was seen 67% of evaluable patients. Conclusion: In this series of HCT recipients, we report overall favorable clinical outcomes for patients with COVID-19 and provide preliminary insights into the clinical course of this disease in this specific population. Funding Statement: None Declaration of Interests: None. Ethics Approval Statement: The hospitals’ Institutional Review Board approved the study.

Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age (> 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1−/pE2F1+ phenotype could indicate an opportunity to minimize chemotherapeutic options in older women; conversely a pAkt1+/pE2F1− phenotype could prompt a more aggressive regimen. Further exploration of this phenotype in younger women with breast cancer and triple-negative breast cancers is warranted.

Thrombocytopenia is a medical condition where blood platelet count drops very low. This drop in platelet count can be attributed to many causes including medication, sepsis, viral infections, and autoimmunity. Clinically, the presence of thrombocytopenia might be very dangerous and is associated with poor outcomes of patients due to excessive bleeding if not addressed quickly enough. Hence, early detection and evaluation of thrombocytopenia is essential for rapid and appropriate intervention for these patients. Since artificial intelligence is able to combine and evaluate many linear and nonlinear variables simultaneously, it has shown great potential in its application in the early diagnosis, assessing the prognosis and predicting the distribution of patients with thrombocytopenia. In this review, we conducted a search across four databases and identified a total of 13 original articles that looked at the use of many machine learning algorithms in the diagnosis, prognosis, and distribution of various types of thrombocytopenia. We summarized the methods and findings of each article in this review. The included studies showed that artificial intelligence can potentially enhance the clinical approaches used in the diagnosis, prognosis, and treatment of thrombocytopenia.

Objectives The primary objective is to determine the prevalence of SARS-COV-2 antibodies persistence among HCWs and specifically among asymptomatic HCW. A secondary objective is to determine the duration of persistent SARS-CoV-2 antibodies post infection and factors affecting this duration. The findings are expected to open the door for further research into the role of SARS-CoV-2 antibodies during the current COVID-19 pandemic. Methodology HCWs were divided into high, intermediate, and low risk based on their type and location of work. All participants filled a questionnaire. Blood samples were obtained for SARS-CoV-2 IgG/total antibodies. A documented SARS-CoV-2 PCR or Anti-SARS-CoV-2 IgG/total antibodies defined the primary outcome. The probability of persistence of antibody was calculated using the Kaplan-Meier estimator. Logistic and Cox regression were used where appropriate. Results A total of 1,111 HCWs were included. The median age 37 years ( IQR: 31–43). More than half (67.2%) were females. The primary outcome was seen in 373 (33.6%) participants with a median age of 36 years ( IQR: 29 - 41). Only 37.2% of those with documented positive SARS-CoV-2 PCR had reactive serology, while only 16.2% of those with reactive serology had documented positive SARS-CoV-2 PCR. Male gender (OR 0.44, P

The World Health Organization-designated Eastern Mediterranean region (EMRO) consists of 22 countries in North Africa and Western Asia with a collective population of over 679 million. The area comprises some of the wealthiest countries per capita income and some of the poorest. The population structure is also unique and contrasts with western countries, with a much younger population. The region sits in the heart of the thalassemia belt. Many countries have a significant prevalence of sickle cell disease, and cancer is on the rise in the region. Therefore, the strategic priorities for the growth and development of hematopoietic stem cell transplantation (HSCT) differ from country to country based on resources, healthcare challenges, and prevalent infrastructure. Thirty-one reporting teams to the Eastern Mediterranean Blood and Marrow Transplantation Group have active HSCT programs in 12 countries; allogeneic transplants outnumber autologous transplants, and the proportion of allotransplants for non-malignant conditions is higher in the EMRO region than in Western Europe and North America. The vast majority (99%) of allotransplants are from matched related donors. Matched unrelated donors and other alternate donor transplants are underutilized. The chance of finding a matched related donor for allografts is higher, with a significant chance of finding matched donors among non-sibling related donors. Reasons for relatively lower rates of transplants compared with other countries are multifactorial. Capacity building, development of newer centers, innovative funding, and better utilization of information technology are required to make transplantation as an accessible modality to more patients. Cost-effectiveness and cost-containment, regulation, and ensuring quality will all be priorities in planning HSCT development in the region.

A systematic review is a specific and reproducible method to search, identify, select, appraise, and summarize all studies relevant to a particular healthcare question. In this paper, we will review the concept of level of evidence, define the terms systematic review and meta-analysis, and outline the steps in performing a systematic review and meta-analysis with an illustrative example. We will also introduce some important concepts in systematic reviews and meta-analyses like heterogeneity, publication bias, forest plots, and quality assessment. Finally, this review will focus on systematic reviews addressing therapeutic research questions.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications.

Objectives Cerebral venous sinus thrombosis (CVST) is a disease with potentially serious consequences. The clinical presentation and outcomes of these patients have not been described in Oman. We sought to describe the clinical characteristics and outcomes of patients with CVST. Methods We conducted a retrospective study in two tertiary care centers in Oman, which included all Omani adults with radiologically confirmed CVST. We recorded and analyzed patients' demographic, clinical, and outcome data. Results Fifty-four patients had radiologically confirmed CVST. The commonest presenting feature was headache (85.0%), followed by focal motor deficits (48.0%) and seizures (27.0%). In this cohort, 24.0% were pregnant or postpartum, 11.0% had an inherited thrombophilia, 11.0% were on hormonal therapy, and 11.0% had systemic lupus erythematous; 38.9% of patients had multiple sinus thrombosis while 35.2% had sigmoid and transverse sinus thrombosis. Antiphospholipid antibody syndrome and infection accounted for 7.0% and 13.0% of causes, respectively, while cancer accounted for 2.0%. No cause was identified in 33.0% of cases. Only 1.9% of patients died, while 29.6% had a residual neurological deficit at hospital discharge. Age was a predictor for residual neurological deficit (p = 0.003). Conclusions Pregnancy and postpartum were the most common predisposing factors for CVST in our cohort. Although the mortality rate is low, the risk of residual neurological deficit remains high. We recommend a prospective study for better characterization and outcome assessment.

Objectives: Haematopoietic stem cell transplantation (HSCT) in Oman started in 1994 at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. Previous studies have suggested that longer driving time to the transplant centre (DTC) independently correlates with worse overall survival (OS). Therefore, this study aimed to examine the impact of DTC on OS and acute graft-versus-host disease (aGvHD). Methods: This retrospective study included all patients who underwent HSCT between February 2006 and December 2016 at SQUH. The DTC was determined using Google Maps (Google LLC., Mountain View, California, USA). The probability of OS was estimated using a Kaplan-Meier estimator and the impact of DTC on OS was compared using a Cox model. Results: A total of 170 patients were included in this study of which 52% were male and 28% were from the Al Batinah region. The mean age was 14.2 ± 12.2 years. The mean haemoglobin, platelet and white blood cell counts before the HSCT were 10.3 ± 1.7 g/dL, 207 ± 131 × 10 9 /L and 5.1 ± 5.9 × 10 9 /L, respectively. The median DTC for those with aGvHD was 84 minutes, which is similar to patients without aGvHD ( P = 0.918). The hazard ratio for DTC as a predictor of OS was 1.0 ( P = 0.901). Conclusion: In this single centre study, DTC did not impact aGvHD or OS in patients post-HSCT. The study was limited by its retrospective design and the small sample size. It is recommended that these results be confirmed in a prospective study. Keywords: Hematopoietic Stem Cell Transplantation; Graft Versus Host Disease; Survival Analysis; Travel; Oman.

Objectives We sought to determine the prevalence, pattern of causative organisms, and mortality of newborns with culture-proven late-onset sepsis (LOS) and to determine and compare the risk factors linked to late-onset gram-positive and late-onset gram-negative sepsis in Sultan Qaboos University Hospital (SQUH). Methods We conducted a cross-sectional retrospective study of data obtained between 1 January 2007 and 31 December 2014 (eight years) from infants in the neonatal intensive care unit (NICU) at SQUH. Infants born in SQUH (inborn) and other institutions (outborn) with positive blood cultures were included in the study. Results The total number of live births and admissions during the study period were 26 289 and 3559, respectively. The total number of infants identified with LOS were 125 of whom 69 (55.2%) were gram-positive, 52 (41.6%) were gram-negative, and four (3.2%) were due to Candida species (spp.). The majority of infants (n = 113, 90.4%) were inborn; 69 (55.2%) were males and 56 (44.8%) were females. The prevalence of LOS among inborn admissions was 4.3 per 1000 live births. Most infections occurred in very low birth weight infants (n = 81, 64.8%). Eleven (8.8%) infants died due to gram-negative sepsis. Klebsiella pneumoniae followed by Pseudomonas aeruginosa were the leading cause of death. Maternal intrapartum antibiotics were the only independent risk factor correlating with gram-negative organisms in multivariate analysis (p = 0.003). Conclusions LOS poses a burden in the NICU, which could be due to the increasing survival of premature babies. The main contributing organisms to LOS are gram-positive bacteria. Klebsiella spp. is a major cause of mortality in LOS. The use of intrapartum antibiotic prophylaxis in mothers might explain the positive correlation of maternal antibiotics as a risk factor with gram-negative infections.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare hematological emergency characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, and multiorgan failure due to autoimmune-mediated deficiency in ADAMTS-13 activity. Currently, plasma exchange, with or without steroids, is the frontline option for the management of aTTP. The treatment should be started promptly once the disorder is clinically suspected. Besides, immunomodulators were studied in patients with aTTP to achieve stable remission and reduce the risk of relapse in patients with suboptimal response to plasma exchange; however, clinical trials showed equivocal results. Published data on early diagnosis, referral, and treatment patterns of aTTP patients in the member nations of the Arabian Gulf Cooperation Council (GCC) are still lacking. Therefore, the present consensus report aimed to present an overview of aTTP situation in GCC by bringing together a panel of experts from three GCC nations, to share their views on current trends and practices regarding aTTP. The experts discussed challenges including the lack of reliable data regarding the incidence of aTTP in GCC and delayed results of ADAMTS-13 activity testing. Limited patient access to tertiary centers and low level of awareness about the aTTP clinical spectrum among general practitioners are other challenges. The experts agreed that there is a need for national and regional consensus regarding the diagnosis and treatment of aTTP in the Gulf region.

We aimed to estimate the nature and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) among Omani patients. We performed a retrospective review of all patients who were tested for PNH by flow cytometry at the Sultan Qaboos University Hospital, Muscat, between 2012 and 2019. Manifestations, treatment modalities, and outcomes were assessed. A total of 10 patients were diagnosed or were on follow-up for PNH (median age 22.5 years). Clinical manifestations included fatigue (80%) and anemia (70%). Six patients had classical PNH with hemolysis, three had PNH in the context of aplastic anemia, and one patient had subclinical PNH. The median total clone size (type II + III) for neutrophils was 95.5 (range: 1.5–97) (FLAER/CD24) and for monocytes was 91.6 (range = 0.04–99) (FLAER/CD14). Four patients had clone sizes > 50% at the time of diagnosis. The median follow-up period of the patients was 62 months (range = 8–204 months). One patient suffered thrombosis. Three patients were on immunosuppressant agents, five were initiated on eculizumab, and four had a bone marrow transplant. No deaths were reported in the cohort. The estimated average incidence of PNH among Omani patients was 1.5 per 5 000 000. PNH is rare in the Omani population. The predominant presentation is hemolytic anemia.

Introduction The oral cavity is one of the most common sites impacted by hematopoietic stem cell transplantation (HSCT) with acute complications including mucositis, bleeding, salivary gland dysfunction, infection, and taste alteration. These complications may result in significant morbidity and can negatively impact outcomes such as length of stay and overall costs. As such, oral care during HSCT for prevention and management of oral toxicities is a standard component of transplant protocols at all centers. The objective of this study was to evaluate the current oral care practices for patients during HSCT at different transplant centers within the Eastern Mediterranean region. Material and methods An internet-based survey was directed to 30 transplant centers in the Eastern Mediterranean region. The survey included five sections asking questions related to (1) transplant center demographics; (2) current oral care protocol used at the center and type of collaboration (if any) with a dental service; (3) use of standardized oral assessment tools and grading systems for mucositis; (4) consultations for management of oral complications; and (5) oral health needs at each center. Data are presented as averages and percentages. Results A total of 16 responses from 11 countries were collected and analyzed, indicating a response rate of 53%. Eight centers reported that a dentist was part of the HSCT team, with four reporting oral medicine specialists specifically being part of the team. Almost all centers (15/16; 93%) had an affiliated dental service to facilitate pre-HSCT dental clearance with an established dental clearance protocol at 14 centers (87%). Dental extraction was associated with the highest concern for bleeding and the need for platelet transfusion. With respect to infection risk, antibiotic prophylaxis was considered in the setting of low neutrophil counts with restorative dentistry and extraction. All centers provide daily reinforcement of oral hygiene regimen. The most frequently used mouth oral rinses included sodium bicarbonate (68%) and chlorhexidine gluconate (62%), in addition to ice chips for dry mouth (62%). The most frequently used mucositis assessment tools were the World Health Organization scale (7/16; 43%) and visual analogue scale for pain (6/16; 37%). Mucositis pain was managed with lidocaine solution (68.8%), magic mouth wash (68.8%) and/or systemic pain medications (75%). Conclusions Scope and implementation of oral care protocols prior to and during HSCT varied between transplant centers. The lack of a universal protocol may contribute to gaps in oral healthcare needs and management for this group of patients. Further dissemination of and education around available oral care guidelines is warranted. Clinical relevance. Considering oral care during HSCT a standard component of transplant protocols, the current study highlights the common oral care practices for patients at centers within the Eastern Mediterranean region.

Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age ( 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1

Hematopoietic Stem Cell Transplantation (HSCT) activity was evaluated in the African (AFR)/EMRO region and compared to the global activity for the years 2006-2013. Data were obtained from 1570 teams in the 6 WHO continental regions. Of these, 29 (1.85%) of all teams were active in 12 of the 68 AFR/EMRO countries. They reported 2.331 (3.3%) of the worldwide 71.036 HSCT, and a transplant rate of 32.8 (TR; HSCT/10 million inhabitants; worldwide 128.5). This reflects still the lowest regional TR despite an increase of 90% since 2006. HSCT activity in AFR/EMRO countries was characterized by a higher use of allogeneic compared to autologous HSCT, an almost exclusive use of family donors, including haploidentical family donors. These findings contrast with the prevalence of autologous over allogeneic HSCT, and a higher frequency of unrelated HSCT in other parts of the world. Of note, the increase by 200% in HSCT for hemoglobinopathies from 2006 to 2013 (72 per year) in the AFR/EMRO region. This reflects the specific role of HSCT for these disease categories with high prevalence and incidence in the AFR/EMRO region. This report provides information for the competent authorities to foster adequate infrastructure. It urges transplant organization to optimize their cooperation.

Objectives Most literature on the frequencies of red blood cell (RBC) phenotypes are published in Europeans and Africans countries, with the frequencies in the Omani population unknown. We sought to determine the prevalence of RBC blood group phenotypes among Omani blood donors. Methods Blood group ABO, RhD type, and phenotyping were performed for 21 blood group antigens on enrolled blood donors. The following antigens were assessed serologically: Rh (C, c, E, e), Kell (K, k, Kpa, Kpb), Kidd (Jka, Jkb), Duffy (Fya, Fyb), Lewis (Lea, Leb), Lutheran (Lua, Lub), MNS (M, N, S, s), and P1. Results A total of 337 Omani blood donors were tested. The most common blood group was O+ (44.9%). Among the tested blood donors studied, 89.3% were RhD positive with R1r being the most common Rh phenotype. The k antigen was found at a frequency of 99.4%, while 4.5% of the blood donors studied were K+. The most common phenotype in the Duffy blood group system was Fy(a-b-), while the most common phenotypes in the Kidd and MNS blood group systems were Jk(a+b+) and M+N-S+s+ at 47.0% and 22.6%, respectively. The Le(a+) and Le(b+) antigens were found in 21.7% and 67.3% of the blood donors, respectively. One Jk(a-b-), one Le(a+b+), and two Lu(a-b-) individuals were identified. Conclusion This is the first study to examine the frequencies of RBC phenotypes among the Omani blood donors. The study's results show Duffy blood group frequencies that resemble what has been reported in the African population, and higher frequencies of the rare null phenotypes compared to European populations.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized immune-mediated condition comprised of a collection of disorders that share specific pathological, serological, and clinical features. IgG4-RD is a fibroinflammatory condition with a tendency to form tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of serum IgG4, which may affect virtually every organ and tissue. IgG4-related ophthalmic disease may present as dacryoadenitis, myositis, or involvement of other orbital tissue. Hypophysitis or pachymeningitis may manifest as cranial neuropathies. The diagnosis of IgG4-RD is based on a typical clinical scenario, supportive laboratory test, expected radiological characteristics, and distinct histopathological and immunohistochemical features. Corticosteroids and immunosuppressives form the mainline treatment.

Objectives: To study and classify the immunophenotypic characteristics of Omani patients diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and to correlate the results with age and gender as well as biological factors (peripheral and bone marrow blast cells percentage). Methods: Fifty cases from both genders and of all ages who fulfilled the inclusion criteria with a diagnosis of T-ALL were included in the study. Correlation of T-ALL subtypes with age, gender, and initial bone marrow and peripheral blood blast cells percentage was assessed using ANOVA. Results: Among the 50 T-ALL patients analyzed, 44 were male and six were female giving a male-to-female ratio of 7:1 (p = 0.007). The average age of patients was 19.2 years with no significant differences in the three disease subtypes. No significant association was seen between the peripheral or bone marrow blast cell percentage and the differentiation stages of the neoplastic clone of T-ALL. All female patients were found to express an immature T-ALL phenotype. Conclusions: This study reports the subtypes of T-ALL in Oman for the first time. It is hoped that this will lead to a better understanding of the disease outcomes.

Introduction and importance Histiocytic sarcoma (HS) is a rare, aggressive malignant neoplasm of hematopoietic cell origin. Primary HS of the proximal humerus, without involvement of lymph nodes or bone marrow, or systemic features, is very rare. Case presentation We report a rare case of primary bony HS of the proximal humerus without bone marrow involvement in a healthy 33-year-old pregnant woman. She was successfully treated with surgical resection during pregnancy and radiotherapy post-delivery. Clinical discussion This is the first report of a patient with primary bony HS during pregnancy. This highlights the fact that although HS is a neoplasm of hemolymphoid cell lineage, it frequently arises in non-lymphoid organs. Conclusion This case emphasizes the importance of a multidisciplinary approach and the need for balancing treatment risk in a patient with primary bone HS during pregnancy., Highlights • Histiocytic sarcoma is a rare aggressive malignant neoplasm of hematopoietic cell origin. • Primary bony histiocytic sarcoma during pregnancy is extremely rare and difficult to diagnose. • Treatment is challenging in a patient with histiocytic sarcoma during pregnancy.

Objectives To evaluate the impact of myeloid antigen expression on complete remission (CR), event-free survival (EFS), and overall survival (OS) in patients with T-cell acute lymphoblastic leukemia (T-ALL) treated with intensive chemotherapy. Methods We retrospectively reviewed consecutive patients diagnosed with T-ALL and treated in Sultan Qaboos University Hospital and Royal Hospital in Oman between 2004 and 2010. The diagnosis of T-ALL was established using French-American-British classification or World Health Organization criteria. Patients were considered having myeloid antigen expression if they expressed CD13, CD33, or both (My+ and My-). Results Of the 39 patients, 38 were included in the study (25 patients with My- and median age of 18.4 years, 13 patients with My+ and median age of 22.0 years). Median follow-up was 12 months. Thirty-two out of the total cohort were eligible for response-rate assessment. Twenty-nine patients (90.6%) achieved CR with one or two courses of chemotherapy with similar CR rates between the two groups (p = 0.880). Twenty-five percent (5/20) of the patients with My- required two courses of induction, whereas 58.3% (7/12) of My+ required two courses of induction and the difference was statistically significant (p = 0.040). In the multivariable analysis; age, gender, initial white blood cell count, central nervous system disease, and myeloid antigen expression were not statistically significant predictors of CR. The EFS and OS were similar between the My+ and My- groups p = 0.180 and p = 0.440, respectively. Conclusions Patients with T-ALL with myeloid antigen expression need more courses of induction; however, rates of CR, EFS, and OS are not different from those without myeloid antigen expression. Larger prospective studies are required to confirm these findings.

Objectives: Manual platelet estimation is one of the methods used when automated platelet estimates are very low. However, the reproducibility of manual platelet estimation has not been adequately studied. We sought to assess the reproducibility of manual platelet estimation following automated low platelet counts and to evaluate the impact of the level of experience of the person counting on the reproducibility of manual platelet estimates. Methods: In this cross-sectional study, peripheral blood films of patients with platelet counts less than 100 × 109/L were retrieved and given to four raters to perform manual platelet estimation independently using a predefined method (average of platelet counts in 10 fields using 100× objective multiplied by 20). Data were analyzed using intraclass correlation coefficient (ICC) as a method of reproducibility assessment. Results: The ICC across the four raters was 0.840, indicating excellent agreement. The median difference of the two most experienced raters was 0 (range: -64 to 78). The level of platelet estimate by the least-experienced rater predicted the disagreement (p = 0.037). When assessing the difference between pairs of raters, there was no significant difference in the ICC (p = 0.420). Conclusions: The agreement between different raters using manual platelet estimation was excellent. Further confirmation is necessary, with a prospective study using a gold standard method of platelet counts.

Objectives: Increased cardiac troponin I (TI) has been suggested to be a sensitive indicator of intraoperative myocardial injury. We investigated the association of transfusion on TI levels post-surgery and outcomes in patients undergoing elective cardiac surgeries. Methods: We conducted a retrospective review of 542 patients. Patients were divided into two groups based on TI levels at 24 hours (TI24) (> 6.5 µg/L vs. ≤ 6.5 µg/L). The impact of transfusion on TI levels was estimated using logistic regression and adjusted for using a multivariable model that included aortic cross-clamp time and preoperative ejection fraction. The effect of TI on the clinical outcomes was examined. Results: Red blood cell (RBC) transfusion was found to be associated with high TI levels (odds ratio (OR) = 2.33, p = 0.007, 95% confidence interval (CI): 1.30–4.30). A trend was observed when aortic cross-clamp time and preoperative ejection fraction were adjusted for (OR = 2.06, p = 0.080, 95% CI: 0.90–4.70). An association was found between aortic cross-clamp time and high TI levels in the multivariable model (OR = 1.01, p = 0.028, 95% CI: 1.00–1.02). Elevated TI levels was associated with higher mortality (OR = 4.15, p = 0.017, 95% CI: 1.29–13.08), renal failure (OR = 2.99, p = 0.004, 95% CI: 1.41–6.32), and increased length of stay in-hospital (OR = 4.50, p = 0.020, 95% CI: 0.69–8.30). Conclusions: RBC transfusion is associated with increased TI24 post-cardiac surgery and worse outcomes, albeit a confounding effect cannot be excluded. Larger studies are required to confirm these findings.

This study aimed to estimate the prevalence of liver fibrosis and assess the risk factors for developing significant liver fibrosis in patients with Thalassemia Major (TM).All patients with TM over the age of 10 years were included in the study.A total of 94 eligible patients underwent 2-D SWE. The median age was 26.7 years. The median of the average 5-year serum ferritin (5yrSF) and liver iron concentration (LIC) assessed by MRI T2* were 1326 µg/L and 6.7 mg/g dw, respectively. Hepatitis C and hepatitis B core antibodies were positive in 38% and 1% of the patients respectively. The proportion of patients with significant fibrosis was 60%. Male gender increased the risk of significant fibrosis (Odds ratio of 0.4; p = .0373). Additionally, the 5yrSF (p = .00661), the LIC (p = .0225) and the lowest LIC of the previous 5 years (p = .0211) were significant. In the multivariable logistic regression model, only 5yrSF (p = .0035) and gender (p = .00984) remained significant.The risk of liver fibrosis is associated with iron overload and gender in patients with TM.

Key PointsQuestionCan poloxamer 188, an agent that is reported to reduce blood viscosity and cell-cell interactions, effectively reduce the duration of vaso-occlusive episodes (painful crises) in hospitalized patients with sickle cell disease? FindingsIn this randomized clinical trial that included 388 children and adults with sickle cell disease, treatment with poloxamer 188 vs placebo resulted in mean time to last dose of parenteral opioids during vaso-occlusive episodes of 81.8 vs 77.8 hours, a difference that was not statistically significant. MeaningAmong patients with sickle cell disease, poloxamer 188 did not significantly shorten the duration of painful vaso-occlusive episodes. ImportanceAlthough 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. ObjectiveTo reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and ParticipantsPhase 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-beta(0) thalassemia, or S-beta(+) thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. InterventionsA 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 MeasuresTime 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. ResultsOf 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT01737814 This phase 3 trial examines the effectiveness of poloxamer 188 in reducing the duration of painful vaso-occlusive episodes in children and adults with sickle cell disease compared with placebo.

Natural killer (NK) cell lymphoproliferative disorders are uncommon and the Epstein-Barr virus (EBV) plays an important aetiological role in their pathogenesis. We report a 20-year-old male with a chronic active EBV infection associated with a NK cell lymphoproliferative disorder which had an unusual indolent course. He presented to the Sultan Qaboos University Hospital in Muscat, Oman, in December 2011 with a history of intermittent fever and coughing. Examinations revealed generalised lymphadenopathy, hepatosplenomegaly, leukocytosis, transaminitis, diffuse bilateral lung infiltrates and bone marrow lymphocyte involvement. A polymerase chain reaction (PCR) test revealed a high EBV viral load in the peripheral blood cells. The patient received a course of piperacillin-tazobactam for Klebsiella pneumoniae , but no active treatment for the lymphoproliferative disorder. However, his lymphocyte count, serum lactate dehydrogenase and liver enzymes dropped spontaneously. In addition, EBV PCR copies fluctuated and then decreased significantly. He remained clinically asymptomatic over the following four years. Keywords: Epstein-Barr Virus Infections; Natural Killer Cell; Lymphoproliferative Disorders; Spontaneous Remission; Case Report; Oman.

Objectives: Structural and functional cardiovascular abnormalities have been reported in adults with osteogenesis imperfecta (OI); however, there is a lack of paediatric literature on this topic. This study aimed to investigate cardiovascular abnormalities in children with OI in comparison to a control group. Methods: This case-control study was conducted at the Sultan Qaboos University Hospital in Muscat, Oman, between May 2013 and August 2014. Data from eight patients with OI and 24 healthy controls were compared using conventional and tissue Doppler echocardiography (TDE). Results: The OI group had significantly lower peak early mitral valve flow velocity ( P = 0.027), peak a-wave reversal in the pulmonary vein ( P = 0.030) and peak early diastolic velocity of the mitral valve and upper septum ( P = 0.001 each). The peak late diastolic velocities of the mitral valve ( P = 0.002) and the upper septum ( P = 0.037) were significantly higher in the OI group; however, the peak early/late diastolic velocity ratios of the mitral valve ( P = 0.002) and upper septum ( P = 0.001) were significantly lower. Left ventricular dimensions and aortic and pulmonary artery diameters were larger in the OI group when indexed for body surface area. Both groups had normal systolic cardiac function. Conclusion: Children with OI had normal systolic cardiac function. However, changes in myocardial tissue Doppler velocities were suggestive of early diastolic cardiac dysfunction. They also had increased left ventricular dimensions and greater vessel diameters. These findings indicate the need for early and detailed structural and functional echocardiographic assessment and follow-up of young patients with OI. Keywords: Children; Osteogenesis Imperfecta; Cardiovascular Abnormalities; Doppler Echocardiography.

OBJECTIVE We performed a systematic review and meta-analysis of randomized clinical trials on adult patients undergoing cardiac surgery and compared the rates of red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusion between the cell saver (CS) and the standard of care groups. METHODS MEDLINE ®, The Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Hematology (ASH) and bibliographies of relevant studies were searched. We used random-effect model. RESULTS Our search strategy returned 624 citations, of which 15 studies were selected. The use of CS did not decrease the rate of RBC transfusion (odds ratio [OR]: 0·69; 95% CI: 0·48-1·00), albeit with a substantial heterogeneity (I2 = 60%). The year of publication explained most of the heterogeneity (P for subgroup effect

Introduction: Von Willebrand Disease (VWD) is the second most common inherited bleeding disorder. There is paucity of the literature describing the prevalence and clinical characteristics of VWD in this part of the world. The aim of the current study is to detect the prevalence, describe the spectrum of the different types of VWD, their mode of presentation, bleeding phenotype and outcome in Oman. Methods: A retrospective cross-sectional study was carried out in the 2 available referral tertiary care facilities in Oman namely; Sultan Qaboos University and the Royal Hospitals. The study included all children and adults diagnosed with VWD in Oman until June 2019. The patients were subtyped as per the International Society of Thrombosis and Haemostasis (ISTH) criteria. Data was collected from the electronic hospital systems in both hospitals. Out of 700 entries of VWD in both hospitals, only 140 were true cases and 560 were tested negative but wrongly labelled. Patients or their next of ken were called and interviewed to obtain the necessary information that was not documented in the electronic system. Results: A total of 140 patients are confirmed to have VWD giving a prevalence of 1:20000. Fifty eight patients are males (41.5%), 82 patients are females (58.5%). Sixty six patients have type I (47%), 38 patients have type II (27%) and 36 patients have type III (26%). The majority of patients 90 (64%) were diagnosed before the age of 20 years and 62 of them (68%) had positive family history of the disease. The most common presentation was recurrent unexplained bruising. As expected, patients with type III tend to have a significant bleeding phenotype with a bleeding score more than 5 in adults and 3 for paediatric patients. All of them were admitted to hospital at some point electively (for surgery) or for bleeding control, however, they were not put on prophylaxis. None of the patients had serious or intra-cranial bleeding. Conclusion: Von Willebrand Disease is not uncommon in Oman with an overall prevalence of 1:20000, however, it is much less than what was originally reported in previous studies in developing countries and the WFH website. The majority of patients are type 1 and have a positive family history of the disease. The disease is more common in females. All patients with type III have abnormal bleeding score and required VW factor replacement at one point. None of the patients had a serious bleed and they are not on prophylaxis. Keywords: Von Willebrand disease, Prevalence, Oman. Disclosures Al-Khabori: AstraZeneca: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Shire (Takeda): Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Background and purpose: There are no currently approved treatments for the vaso-occlusive crises (VOC) associated with sickle cell disease (SCD). In addition to causing pain, vaso-occlusion and the resulting hypoxia cause a reduction in overall life expectancy and increase chronic morbidity. Sevuparin is a novel, non-anticoagulant, low-molecular weight heparin analogue, with a preclinical multi-modal activity profile against VOC relevant targets (i.e. P- and L-selectin, thrombospondin, Von Willebrand factor, fibronectin). Due to its low risk for bleeding side effects, sevuparin can be dosed at levels that were previously unattainable with heparinoids. The present study evaluated whether sevuparin could shorten the time with VOC in hospitalized SCD patients compared to placebo. Patients and methods: This phase II, global, multicenter, randomized, double-blind, placebo-controlled and parallel group clinical trial enrolled patients aged 12 to 50 with a diagnosis of SCD (HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia). The study recruited patients across 22 sites in 8 countries (Netherlands, Belgium, Turkey, Oman, Bahrain, Lebanon, Saudi Arabia, and Jamaica). Patients with VOC received sevuparin or placebo (1:1) along with standard of care (SoC) therapy with a requirement for parenteral opioid use. The primary endpoint was time to VOC resolution, measured as the time from IMP start until resolution by fulfilment of the two following criteria: a) freedom from parenteral opioid use (8 ± 2 hours), b) readiness for discharge as judged by the patient or physician (whichever occurred first). In addition to assessing safety, main secondary efficacy measures were related to pain and opioid use. The sample size of 120 VOC resolution events was determined based on an assumed between-arm hazard ratio of 0.60. Results: Overall, 147 subjects were randomized (144 dosed) to sevuparin, n=71 (69); or placebo n=76 (75). The median age of subjects entering the study was 22 years with 72% adults and 62,5 % males. Treatment groups were generally balanced with respect to demographic and baseline characteristics. Sevuparin, infused continuously at 18 mg/kg/day, did not confer any benefit over placebo in the primary endpoint of time to VOC resolution (ITT Cox proportional HR 0.89 (95% CI 0.61-1.30; p = 0.554; Figure 1a), which was also reflected by the secondary endpoint analyses (exemplified in Figure 1b). Most AEs were mild to moderate and transient. The number of SAEs was slightly higher in the placebo group (21/17 [22.4%]; one fatal case with hyperhemolytic crisis) than in the sevuparin group (16/15 [22.1%]). The most commonly reported treatment emergent AEs (TEAEs) are displayed in Table 1. No clinically meaningful differences, imbalances or trends were apparent in TEAEs, laboratory parameters, vital signs, physical examination and ECG data across treatment groups. Conclusions: In this study, one of the largest VOC studies run to date, sevuparin failed to show an improvement of the VOC resolution time and associated measures (pain, opioid use, etc) in patients hospitalized with acute VOC. These results were surprising given both the promise from preclinical models and the clinical efficacy seen with selectin inhibition. It is possible that once full-blown, an acute VOC cannot be limited by sevuparin's mode of action (MoA). The understanding of sevuparin's MoA combined with this negative result may contribute to the notions of VOC causative factors and help inform future therapeutics targeting the VOC. The study is also important given its size and the high patient representation from the eastern Mediterranean and Middle Eastern regions, where SCD is of high prevalence. The comparison of this data with the available data from other VOC studies will be important in helping understand both regional and genetic differences in treatment practices and response to therapeutics. In conclusion, the present study showed that sevuparin treatment was not effective in acute VOC. However, sevuparin's promising safety profile and broad MoA including p-selectin inhibition, may warrant further exploration in the prodromal setting, especially given that sevuparin may be dosed by the patient at home in a convenient, subcutaneous format. Acknowledgements: Modus is grateful for the contributions from Ergomed, the Arabian Gulf University, the study sites, as well as to the patients for participating in this study. Disclosures Al-Khabori: Shire (Takeda): Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria; AstraZeneca: Honoraria. Abboud:CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Other: Travel support; Modus: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Inati:Novonordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Research Funding; AstraZeneca: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kristensen:Modus Therapeutics: Employment. Donnelly:Modus Therapeutics: Employment. Ohd:Modus Therapeutics: Employment.

Objectives: Sickle Cell Disease (SCD) is an inherited hemoglobinopathy with multiple complications including stroke. It is observed that siblings with SCD have an increased risk of stroke if there was a sibling in the family with SCD and stroke (Driscoll M C, Blood, 2003). Human Leukocyte Antigen (HLA) is extremely variable among individuals and certain HLA alleles have previously been associated with a number of diseases. It has been shown that HLA-DRB1*0301, HLA-DRB1*0302 and HLA-DQB1*0201 increase the risk of stroke and HLA-DRB1*1501 and HLA-DQB1*0602 lower the risk of stroke in patients with SCD (Styles L, Blood, 2000). These alleles are not common in all populations. We therefore planned to assess the impact of other HLA alleles on the risk of stroke in patients with SCD. Methods: This is a retrospective case-control study conducted at Sultan Qaboos University Hospital. We included all adult and pediatric patients with SCD and diagnosed with stroke using CT/MRI of the brain. The study included patients diagnosed during the period of 1995 to 2015. HLA typing was performed using molecular techniques. HLA alleles with a frequency of at least 5% were selected for analysis. Association studies were performed using Fisher Exact test. All statistical tests were performed using R program (version 3.1.2). Results: A total of 244 patients were included (66 patients with SCD and stroke [cases] and 178 patients with SCD with no stroke. The median age was 26 years (Interquartile Range [IQR]: 19-32) and 23 (IQR: 17-29 ) for cases and controls respectively. The median hemoglobin, mean corpuscular volume, hemoglobin S level and lactate dehydrogenase level was 9 g/dL, 70 fL, 70% and 400 U/L respectively for the cases, and 9 g/dL, 60 fL, 70% and 400 U/L respectively for the control. The most frequent HLA-A allele was HLA-A*02 (24%) which did not impact the risk of stroke (Odds Ratio [OR]: 1.59, 95% Confidence Interval [CI]: 0.84-3.02) as were the other tested HLA-A alleles (all CIs crossed OR of 1.00). The most frequent HLA-B allele was HLA-B*51 (15%) which did not impact the risk of stroke (OR: 0.89, 95% CI: 0.43-1.85) as were the other tested HLA-B alleles (all CIs crossed OR of 1.00). The most frequent HLA-C allele was HLA-C*04 (17%) which did not impact the risk of stroke (OR: 1.34, 95% CI: 0.67-2.65); however, HLA-C*06 (OR: 2.37, 95% CI: 1.01-5.54) increased the risk of stroke while HLA-C*07 protected from stroke (OR: 0.35, 95% CI: 0.13-0.93). None of the other HLA-C alleles were statistically significant (all CIs crossed OR of 1.00). The most frequent HLA-DRB1 allele was HLA-DRB1*16 (18%) which did not impact the risk of stroke (OR: 1.02, 95% CI:0.51-2.03) as were the other tested HLA-DRB1 alleles (all CIs crossed OR of 1.00). Conclusions: HLA-C*06 is associated with an increased risk of stroke in patients with SCD while HLA-C*07 is protective from stroke in these patients. Early identification of high-risk patients would be beneficial for preventive intervention, such as chronic transfusion or bone marrow transplantation. The impact of these HLA alleles should be validated in other populations. Disclosures Al-Khabori: Shire (Takeda): Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; SOBI: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; NovoNardisk: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.