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Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Abstract Leukemia burden is growing in the Gulf Council Cooperation (GCC) countries. Nonetheless, there is no unified protocol for managing adult acute lymphoblastic leukemia (ALL) patients in the GCC‐countries. Therefore, the GCC Adult‐ALL Treaters working group developed this consensus to address the adult‐ALL treatment protocols in the GCC‐countries and related toxicities' management. Besides, the consensus aimed to highlight the current unmet needs and treatment gaps and provide recommendations to optimize adult‐ALL care and patient‐centered communication. A three‐step modified Delphi method to develop evidence‐based recommendations through two‐voting rounds and in‐between virtual meetings are used in the manuscript development. A 12 experts' panel from five GCC‐countries and two international experts were invited to participate in this consensus. This consensus consisted of 35‐statements that highlighted the experts' recommendations to optimize ALL adults' care in the first line setting and manage pediatric or pediatric‐inspired regimens‐related toxicities. Besides, guidance was provided for future research direction and improve patient‐centered communication. In conclusion, the adult‐ALL management landscape is evolving, and the current evidence highlights better response and survival outcomes with pediatric or pediatric‐inspired regiments. Therefore, protocols are needed to optimize the adult‐ALL management in the GCC and tailored clinical‐trials findings according to the GCC patients' characteristics and local‐healthcare infrastructure.

Objectives: To estimate the incidence, risk factors, and outcome of cytomegalovirus (CMV) infection during the first year following hematopoietic stem cell transplant (HSCT) among Omani patients. Methods: This retrospective study included allogenic HSCT recipients between January 2006 and December 2018. We investigated the possible factors associated with CMV infection and CMV impact on one-year mortality.Results: Among 556 recipients of allogenic HSCT, 308 (55.4%) were male, the median age was 12 years, and 366 (65.8%) had benign conditions. One-year after transplants, the prevalence of CMV infection was 59.4%, and that of CMV disease was 1.8%. Multivariate analyses revealed significant relationships between CMV infection and haploidentical transplant (p =0.006), graft versus host disease (p =0.013), myeloablative conditioning (p =0.001), and patient age ≥ 12 years (p < 0.001). CMV infection was associated with an increased risk of one-year mortality (p =0.001). One-year overall mortality was 8.3%. Conclusions: The incidence of CMV infection in this Omani cohort was comparable with earlier findings, but the disease incidence and overall mortality were lower. Older age, haploidentical transplant, myeloablative conditioning, and graft versus host disease were significantly associated with a higher risk of CMV infection. In addition, CMV infection was associated with an increased risk of overall mortality in the first year post-transplant. Our findings support early initiation of preemptive therapy at low-level CMV viremia.

IntroductionCoronary artery disease (CAD) management in the setting of immune thrombocytopenia (ITP) remains very challenging to clinicians as a reasonable balance between bleeding and thrombosis risks needs to be achieved, and the evidence guiding such management is scarce.MethodsWe conducted a systematic review following the PRISMA guidelines to summarize the available literature on the management and outcomes of CAD coexisting with ITP. We searched PubMed and Embase for studies published in English exploring CAD and ITP management until 05 October 2022. Two independent reviewers screened and assessed the articles for inclusion. Patients' characteristics, CAD treatment modalities, ITP treatment, and complications were reported.ResultsWe identified 32 CAD cases, among which 18 cases were revascularized with percutaneous coronary intervention (PCI), 12 cases underwent coronary artery bypass graft surgery (CABG), and two cases were managed conservatively. More than 50% were men, with a mean age of 61 ± 13 years and a mean baseline platelet count of 52 ± 59 × 109/L. Irrespective of the revascularization modality, most patients were treated with either corticosteroids alone, intravenous immunoglobulins (IVIG) alone, or in combination. Among those who underwent PCI, two patients had bleeding events, and one patient died. Similarly, among those with CABG, one patient developed bleeding, and one patient died.ConclusionWe found that revascularization with either PCI or CABG with the concurrent use of corticosteroids and/or IVIG for ITP was feasible, with an existing non-negligible risk of bleeding and mortality.

Objectives: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most encountered abnormality of red blood cell metabolism worldwide and has a high prevalence in Oman. The objective of the study was to characterize the mutation variants of G6PD deficiency in a cohort of the Omani population with partial and complete enzyme deficiency. Methods: This prospective study included newborns and children less than one year of age with partial or complete G6PD enzyme deficiency identified on routine screening using a fluorescent spot test from 31 January 2017 to 12 September 2017 in Sultan Qaboos University Hospital. The identified samples were analyzed for the presence of C563T, G1003A, and other mutations using direct DNA sequencing of the polymerase chain reaction. Results: Out of 3679 newborn samples screened, 21.0% were found to have complete or partial G6PD enzyme deficiency. A total of 145 participants were included in the genetic analysis, of which 133 (91.7%) were completely deficient in G6PD enzyme activity and 12 (8.3%) had partial deficiency. The Mediterranean variant (C563T) was identified in 129 (89.0%). Other variants were found as follows: eight (5.5%) had variant A-, three (2.1%) had the Chatham variant (G1003A), one (0.7%) had the Cosenza variant, and one (0.7%) had exon 11 variant. No mutation was found in two subjects. Conclusions: The most common mutation in the Omani population is the Mediterranean mutation (C563T) followed by the variant A- mutation. However, not all participants were found to have a mutation.

BackgroundThe outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT.MethodsThis multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022.ResultsThe median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53).ConclusionsMortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p

Objectives: The primary objective is to determine the prevalence of SARS-CoV-2 antibodies persistence among HCWs and specifically among asymptomatic HCWs. 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 1111 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 < 0.001) and older age (OR 0.98, P < 0.019) were associated with a lower risk of acquiring SARS-CoV-2 infection. The probability of persistent SARS-CoV-2 antibodies at six months was 60.2% (95% CI: 49.5%–73.1%). Omanis had a higher probability of losing the antibody than others (HR 2.63, P = 0.021). Conclusion: We report a high prevalence of anti-SARS-CoV-2 antibodies among HCWs in Oman, specifically among asymptomatic HCWs. Community was the most likely source of infection. Therefore, the society must adhere to the roles and regulations set to reduce the risk of transmission. We demonstrate a high percentage of seroconversion post initial infection, and the persistence of SARS-CoV-2 antibodies at six months in more than half of those previously infected. We demonstrated a new interesting finding of fast decline of SARS-CoV2 antibody levels over time among different nationalities and this requires further research.

Abstract Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value

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 naïve 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 naïve CD4 T cells can be used as independent immunological predictors of poor outcomes in COVID-19 patients to prioritize critical care and resources.

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.

This is a systematic review and meta-analysis evaluating the prognostic significance of epigenetic mutations on the overall survival (OS) in Acute Myeloid Leukemia (AML). We searched for studies evaluating epigenetic mutations in AML (up to November 2018) in PubMed, Trip database and Cochrane library. Hazard ratio (HR) of outcomes were extracted, and random-effects model was used to pool the results. A total of 10,002 citations were retrieved from the search strategy; 42 articles were identified for the meta-analysis (ASXL1 = 7, TET2 = 8, DNMT3A = 12, IDH =15), with fair to good-quality studies. The pooled HR was 1.88 (95% CI: 1.49−2.36) for ASXL1 mutation, 1.39 (95% CI: 1.18−1.63) for TET2 mutation, 1.35 (95% CI 1.16-1.56) for DNMT3a and 1.54 (95% CI: 1.15-2.06) for IDH mutation. However, there was a substantial heterogeneity in the DNMT3a and IDH studies. In conclusion epigenetic mutations in ASXL1, TET2, DNMT3a and IDH adversely impact OS in patients with AML albeit with considerable heterogeneity and possibly publication bias. Further studies are required to address these limitations.

A systematic review is a specific and reproducible method to search, identify, select, appraise, and summarize all studies relevant to a particular health care 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.

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.

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.

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P

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.

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: 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.

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: 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.

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 × 109/L and 5.1 ± 5.9 × 109/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: 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.

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.

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: Transfusions are a common medical intervention. Discussion of the benefits, risks and alternatives with the patient is mandated by many legislations prior to planned transfusions. At the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, a written transfusion consent policy was introduced in March 2014. This was the first time such a policy was implemented in Oman. This study therefore aimed to assess adherence to this policy among different specialties within SQUH. Methods: The medical records of patients who underwent elective transfusions between June and August 2014 were reviewed to assess the presence of transfusion consent forms. If present, the consent forms were examined for completeness of patient, physician and witness information. Results: In total, the records of 446 transfused patients (299 adult and 147 paediatric patients) were assessed. Haematology patients accounted for 50% of adult patients and 71% of paediatric patients. Consent was obtained for 75% of adult and 91% of paediatric patients. The highest adherence rate was observed among adult and paediatric haematology specialists (95% and 97%, respectively). Consent forms were correctly filled out with all details provided for 51% and 52% of adult and paediatric patients, respectively. Among inadequately completed forms, the most common error was a lack of witness details (20–25%). Conclusion: In most cases, the pre-transfusion consent policy was successfully adhered to at SQUH. However, further work is required to ensure full compliance with the consent procedure within different specialties. Implementation of transfusion consent in other hospitals in the country is recommended.

Objectives: Transfusion is a common intervention that mandates the discussion of benefits, risks, and alternatives to planned transfusions. In Oman, transfusion consent was first introduced at the Sultan Qaboos University Hospital in March 2014. We sought to evaluate our physicians’ opinions, attitudes, and perception of the transfusion consent process. Methods: Attending physicians of different specialties were invited to complete an anonymous survey on transfusion consent. Results: A total of 114 physicians responded to the survey. Transfusion benefits and risks were explained regularly by 91% and 87% of the surveyed physicians, respectively. On the other hand, alternatives were declared by only 38%. Discomfort with the consent process was admitted by 10% of the physicians. There was no statistically significant association between discomfort in obtaining the consent and the physician seniority (p = 0.801), nor their specialties (p = 0.623). The importance of the consent process was acknowledged by 80% of surveyed physicians, who supported its implementation in other hospitals. Conclusion: This survey reflects positive attitudes of the surveyed physicians on the importance of transfusion consent. However, actions are required to achieve physicians’ full ease with the process and to ensure that transfusion alternatives are discussed. We advocate implementation of transfusion consent in other hospitals in Oman.

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.

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.

Objectives: To assess the response rate and duration of response in patients with chronic immune thrombocytopenia (ITP) receiving rituximab. Methods: We retrospectively analyzed 32 consecutive patients with chronic ITP who were treated in two tertiary centers in Oman. Response assessment was based on the American Society of Hematology criteria. Results: Nineteen patients (59%) had an initial response. However, six of the 19 patients lost their response leaving 13 patients with long-lasting remissions. The median age at diagnosis was 25 years (range 14–58). The median time from diagnosis to rituximab therapy was 21 months. The median follow-up after starting rituximab was 26 months. The overall cumulative response rate was 59% (complete response 44%, partial response 15%) and the median time to respond was 30 days with a response rate of 44% at four weeks. In all responders, the cumulative rate of loss of response was 32% with a median time to lose response of 54 months. Conclusions: The use of rituximab in ITP achieves high response rate and long remission duration. Our study was limited by the small sample size and further larger prospective studies are recommended.

The recognition and management of transfusion reactions (TRs) are critical to ensure patient safety during and after a blood transfusion. Transfusion reactions are classified into acute transfusion reactions (ATRs) or delayed transfusion reactions, and each category includes different subtypes. Different ATRs share common signs and symptoms which can make categorisation difficult at the beginning of the reaction. Moreover, TRs are often under-recognised and under-reported. To ensure uniform practice and safety, it is necessary to implement a national haemovigilance system and a set of national guidelines establishing policies for blood transfusion and for the detection and management of TRs. In Oman, there are currently no local TR guidelines to guide physicians and hospital blood banks. This paper summarises the available literature and provides consensus guidelines to be used in the recognition, management and reporting of ATRs.

Objective: This study aims to evaluate the knowledge and attitudes of Oman Medical Specialty Board (OMSB) residents towards Evidence-Based Medicine (EBM). Methods: This cross sectional study was conducted on all OMSB residents through a self-administered online questionnaire between October 2012 and March 2013. An electronic survey was designed to identify and determine residents' knowledge and attitudes toward the use of EBM. Results: The survey was completed by 93 (21%) OMSB residents, 76 (82%) of whom took part in continuing education courses and 50 (54%) belonged to professional practice-oriented organizations. On average, the residents were reportedly involved in patient care for approximately 70% (Standard Deviation [SD] 17%) of their time, while 14% (SD 12%) participated in research activities. The results showed that 53 respondents (57%) were competent users of medical search engines compared to 23 residents (25%) who rated their skills as neutral. Sixteen percent of the respondents strongly agreed and 46% only agreed that the facility supports the use of current research in practice. Fourteen percent strongly agreed and fifty-three percent only agreed that the foundation of EBM is part of OMSB academic preparation. On the other hand, 17% of the respondents thought that insufficient time is always a barrier against EBM, while another 27% perceived insufficient time as a usual barrier. The lack of information resources was reported to always be a barrier in 11% of the respondents while 32% thought that it usually acts as a barrier. Conclusion: Time constraints and skills in EBM were found to be the two major obstacles. This study was, however, limited by the low response rate of the survey; thus larger studies with a previously validated questionnaire should be conducted in the future.

Objective: The aim of this study is to compare the neonatal outcomes of monochorionic and dichorionic twin pregnancies.Methods: A retrospective cohort study involving 51 twin pregnancies followed and delivered at Sultan Qaboos University Hospital was conducted between January 2006 and December 2011.Result: Thirty six (71%) pregnancies were dichorionic diamniotic (DCDA), 14 (27%) were monochorionic diamniotic (MCDA), and one (2%) was monochorionic monoamniotic (MCMA). The antepartum complications noted in the 15 monochorionic twins were discordant fetal growth in 2 (14%) cases, low birth weight in 11 (73%) babies, pre-eclampsia in three mothers (21%) and twin to twin transfusion syndrome in four (29%) cases. Fetal respiratory distress affected eight (57%) of the pregnancies. Six (40%) twin sets were delivered before 30 weeks, 4 (27%) sets at 31 to 32 weeks, 2 (13%) sets at 34-35 weeks, 2 (13%) sets at 36-37 weeks, and 1 (7%) at 37-38 weeks. Fifteen mothers delivered 16 live infants, 9 (30%) stillbirths and 5 (17%) died after birth. Most neonatal deaths were due to neonatal sepsis and pulmonary hypoplasia. Dichorioinic twins, (DC) morbidity was seen in 11% and 40% for monochoroinic twins (MC). Mortality rate was 17% for DC and 47% for MC twins.Conclusions: Perinatal morbidity and mortality remain high among monochorionic twins. This is likely due to frequent twin-to-twin transfusion syndrome, prematurity, fetal growth restriction and intrauterine fetal death. Improved fetal and neonatal management may result in improved outcomes.

Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX) side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female) with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s) in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline), feeling unwell (2), severe diarrhea (1), pregnancy (1), death unrelated to chelator (2) and rise in serum transaminases (2). Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013).Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.