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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

Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT.This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes.A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively).GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

Background Safe handling of oral anticancer agents is of great concern. There is a lack of clear, national guidelines on how patients can safely handle and dispose of unwanted medications. We aimed to evaluate the safe handling, storage, and disposal of oral anticancer drugs among cancer patients and caregivers at home. Method This cross-sectional survey of adult cancer patients (or their adult caregivers) used a closed-ended questionnaire from May 2019 to March 2020. Results A total of 257 patients (50 ± 15 years; range: 18–93 years) were enrolled; however, only 91% (233/257) reported self-administering oral anticancer medications. Caregivers were more likely to administer oral anticancer agents for patients ≥60 years than those Conclusion While two-thirds of patients stored their oral anticancer medications properly, more than half used inappropriate handling procedures. Disposal practices were inconsistent and did not adhere to the reported international guidelines.

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.

Introduction Stem cell enumeration by the hematopoietic progenitor cells (HPC) mode is a novel method available from Sysmex XN2000 hematology analyzer. A small amount of blood (190 μL) is required, and the results are available in a few minutes without manual gating or presample treatment. The present study compares stem cell measurements using XN2000 analyzer HPC mode and FC500 flow cytometry analyzer using peripheral blood (PB) specimens and apheresis products. Methods In this prospective study, CD34-positive cell counts were enumerated using an FC500 flow cytometry analyzer and compared with XN2000 Sysmex analyzer (XN-HPC mode) in the same samples. Results were compared using Bland-Altman plots. Results A total of 103 samples were used. In the PB samples, the median HPC count and CD34-positive cells were 83.5 × 106 /L and 78.0 × 106 /L, respectively. The mean Bland-Altman difference was 4.5 × 106 /L (Limits: -51.7 to 60.7 × 106 /L), with a Pearson's correlation of 0.79. In the apheresis products, the median HPC count and CD34-positive cells were 1468 × 106 /L (IQR: 1049 - 1960 × 106 /L) and 1327 × 106 /L (IQR: 910 - 2001 × 106 /L), respectively. The mean Bland-Altman difference was 179.0 × 106 /L (Limits: -2022.2 - 2380.2 × 106 /L), with a Pearson's correlation of 0.58. Conclusion The XN-HPC mode has an excellent correlation and minimal disagreement for stem cell enumeration in PB compared with flow cytometry and could replace it. There is high disagreement in apheresis products, and therefore, the XN-HPC mode cannot be recommended.

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted 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.

Summary 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, HbSβ0-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.

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.

Most anticancer agents show wide variability in pharmacokinetics (PK) and have a narrow therapeutic index which makes fixed dosing suboptimal. To achieve the best therapeutic outcomes with these agents, many studies have postulated using PK or therapeutic drug monitoring (TDM)-guided dosing. However, multiple factors contribute to the variability in PKs making the application of TDM in practice challenging. Also, despite the known association with clinical outcomes, standard guidelines on PK-guided dosing are lacking for most agents. Understanding the factors that contribute to PK variability and their impact is essential for dose individualization. The purpose of this review is to discuss the factors that contribute to the PK variability of anticancer agents and the challenges faced in practice when individualizing doses for certain widely used agents. Searching the literature has identified several gaps and efforts are needed to ensure better targeting of cancer therapeutics.

Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplant (HSCT). Busulfan has a narrow therapeutic index and its concentration was found to correlate with VOD. Our primary objective was to assess the association between busulfan clearance and VOD in HSCT patients. In this retrospective analysis, we included patients who received their HSCT between 2003 and 2014 and followed at Sultan Qaboos University Hospital. All patients who received dose-targeted busulfan-containing conditioning were included. Target steady-state concentration (Css) was 800-900 ng/ml. VOD was assessed using modified Seattle criteria. The impact of busulfan clearance on VOD was analyzed using univariable logistic regression model. Seventy-three patients were included with a mean age of 15 years. Of those, 47% were transplanted for hematological malignancies and 53% for inherited hemoglobinopathies. Target Css was achieved in 85% of patients. The rate of VOD was 17%. There was no significant impact of busulfan clearance (p = 0.919) or area-under-the-concentration-time-curve (p = 0.275) on VOD. Targeting busulfan Css into narrow therapeutic range may have accounted for the findings. The risk of VOD might be related to other factors such as the genetic background, and more studies are required to investigate these factors.

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

BACKGROUND AND OBJECTIVES Blood group genotyping has been used in different populations. This study aims at evaluating the genotypes of common blood group antigens in the Omani blood donors and to assess the concordance rate with obtained phenotypes. MATERIAL AND METHODS Blood samples from 180 Omani donors were evaluated. Samples were typed by serological methods for the five blood group systems MNS, RH (RHD/RHCE), KEL, FY and JK. Samples were genotyped using RBC-FluoGene vERYfy eXtend kit (inno-train©). Predicted phenotypic variants for 70 red blood cell antigens among the MNS, RH (RHD/RHCE), KEL, FY, JK, DO, LU, YT, DI, VEL, CO and KN blood group systems were assessed. RESULTS Simultaneous phenotype and genotype results were available in 130 subjects. Concordance rate was >95% in all blood group systems with exception of Fy(b+) (87%). Homozygous GATA-1 mutation leading to erythroid silencing FY*02N.01 (resulting in the Fy(b-)ES phenotype) was detected in 81/112 (72%) of genotyped samples. In addition, discrepant Fyb phenotype/genotype result was obtained in 14/112 samples; 13 of which has a heterozygous GATA-1 mutation and one sample with a wild GATA genotype. D and partial e c.733C>G variants expressing the V+VS+ phenotype were found in 22/121 (18.2%) and 14/120 (11.7%) of the samples, respectively. Di(a-b+), Js(a-b+), Yt(a+b-) and Kn(a+b-) genotype frequencies were 99.4%, 95.8%, 91.9% and 97.7%, respectively. CONCLUSION In conclusion, we report a high frequency of FY*02N.01 allele due to homozygous c.-67T>C GATA-1 single-nucleotide variation. This is the first study reporting the detailed distribution of common and rare red cell genotypes in Omani blood donors.

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.

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources.

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

The consequence of regular blood transfusion in patients with thalassemia major (TM) is iron overload. Herein, we report the long-term impact of chelation on liver iron concentration (LIC) and cardiac T2* MR in patients with TM. This is a retrospective cohort study over 10 years of adolescents and adults with TM aged at least 10 years who had their first cardiac T2* MR between September 2006 and February 2007. One-year chelation therapy was considered the unit of analysis. A total of 99 patients were included in this study with a median age of 18 years. The median cardiac T2* MR and LIC at baseline were 19 ms and 11.6 mg/g dw, respectively. During follow-up, 18 patients died and six underwent successful bone marrow transplantation. Factors associated with decreased survival were older age (HR 1.12, p = 0.014) and high risk cardiac T2* (HR 8.04, p = 0.004). The median cardiac T2* and LIC significantly improved over the 10-year follow-up period (p = 0.000011 and 0.00072, respectively). In conclusion, this long-term “real-life” study confirms that low cardiac T2* adversely impacts the overall survival in patients with TM. Higher baseline LIC predicts a larger reduction in LIC, and lower baseline cardiac T2* predicts a larger improvement in T2*.

Objectives This study was conducted to assess transfusion knowledge between different specialty board residents and to identify areas of need for further education. Background Physicians' knowledge of transfusion medicine (TM) is critical for patients' safety. Many clinicians who are involved in day-to-day transfusion practice have little or no formal training in TM. There are no studies to assess physician's TM knowledge locally. Methods A comprehensive anonymous survey was developed to assess baseline TM knowledge of all the residents. The survey is composed of different sections, including a questionnaire on resident's demographics, resident's self-reflection on their TM knowledge and 30 multiple choice questions addressing basic and clinical TM knowledge in two major domains: component selection and transfusion practice and transfusion safety and transfusion reactions. Finally, the residents' opinion on educational needs was assessed. Results A total of 130 residents were surveyed. The lowest score obtained among the two major domains assessed was in the transfusion safety and transfusion reaction domain, with a mean score of 4·34 of 15 (SD ± 3·27). The mean score obtained on component selection and transfusion practice was 7·1 of 15 (SD ± 3·74). A substantial proportion of the residents (74·7%) admitted minimal baseline knowledge in the field of TM. Finally, 94·5% of the residents admitted the need for more education during residency, whereas 49·5% thought additional education is required during the first year of practice. Conclusion This survey shows serious TM knowledge deficiency and indicates the need for additional education among all physicians during training.

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.

Background: Glanzmann's thrombasthenia (GT) is an autosomal, qualitative platelet disorder that is genetically recessive. This report is about a patient with GT, complicated by infertility...