Ahmed Alaskar

Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.

Human Chorionic Villous Mesenchymal Stem Cells Modify the Functions of Human Dendritic Cells, and Induce an Anti-Inflammatory Phenotype in CD1+ Dendritic Cells

BackgroundMesenchymal stem cells derived from the chorionic villi of human term placenta (pMSCs) have drawn considerable interest because of their multipotent differentiation potential and their immunomodulatory capacity. These properties are the foundation for their clinical application in the fields of stem cell transplantation and regenerative medicine. Previously, we showed that pMSCs induce an anti-inflammatory phenotype in human macrophages. In this study, we determined whether pMSCs modify the differentiation and maturation of human monocytes into dendritic cells (DCs). The consequences on dendritic function and on T cell proliferation were also investigated.MethodsInterleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to stimulate the differentiation of monocytes into immature dendritic cells (iDCs), which were subsequently co-cultured with pMSCs. Lipopolysaccharide (LPS) was used to induce maturation of iDCs into mature dendritic cells (mDCs). Flow cytometry and enzyme-linked immunosorbent assays (ELISA) were used to quantify the effect pMSC co-culturing on DC differentiation using CD1a, a distinctive marker of DCs, as well as other molecules important in the immune functions of DCs. The phagocytic activity of iDCs co-cultured with pMSCs, and the effects of iDCs and mDC stimulation on T cell proliferation, were also investigated.ResultsMonocyte differentiation into iDCs was inhibited when co-cultured with pMSCs and maturation of iDCs by LPS treatment was also prevented in the presence of pMSCs as demonstrated by reduced expression of CD1a and CD83, respectively. The inhibitory effect of pMSCs on iDC differentiation was dose dependent. In addition, pMSC co-culture with iDCs and mDCs resulted in both phenotypic and functional changes as shown by reduced expression of costimulatory molecules (CD40, CD80, CD83 and CD86) and reduced capacity to stimulate CD4+ T cell proliferation. In addition, pMSC co-culture increased the surface expression of major histocompatibility complex (MHC-II) molecules on iDCs but decreased MHC-II expression on mDCs. Moreover, pMSC co-culture with iDCs or mDCs increased the expression of immunosuppressive molecules [B7H3, B7H4, CD273, CD274 and indoleamine-pyrrole 2,3-dioxygenase (IDO). Additionally, the secretion of IL-12 and IL-23 by iDCs and mDCs co-cultured with pMSCs was decreased. Furthermore, pMSC co-culture with mDCs decreased the secretion of IL-12 and INF-γ whilst increasing the secretion of IL-10 in a T cell proliferation experiment. Finally, pMSC co-culture with iDCs induced the phagocytic activity of iDCs.ConclusionsWe have shown that pMSCs have an inhibitory effect on the differentiation, maturation and function of DCs, as well as on the proliferation of T cells, suggesting that pMSCs can control the immune responses at multiple levels.

Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells from Decidua Basalis of Human Term Placenta

Mesenchymal stem cell (MSC) therapies for the treatment of diseases associated with inflammation and oxidative stress employ primarily bone marrow MSCs (BMMSCs) and other MSC types such as MSC from the chorionic villi of human term placentae (pMSCs). These MSCs are not derived from microenvironments associated with inflammation and oxidative stress, unlike MSCs from the decidua basalis of the human term placenta (DBMSCs). DBMSCs were isolated and then extensively characterized. Differentiation of DBMSCs into three mesenchymal lineages (adipocytes, osteocytes, and chondrocytes) was performed. Real-time polymerase chain reaction (PCR) and flow cytometry techniques were also used to characterize the gene and protein expression profiles of DBMSCs, respectively. In addition, sandwich enzyme-linked immunosorbent assay (ELISA) was performed to detect proteins secreted by DBMSCs. Finally, the migration and proliferation abilities of DBMSCs were also determined. DBMSCs were positive for MSC markers and HLA-ABC. DBMSCs were negative for hematopoietic and endothelial markers, costimulatory molecules, and HLA-DR. Functionally, DBMSCs differentiated into three mesenchymal lineages, proliferated, and migrated in response to a number of stimuli. Most importantly, these cells express and secrete a distinct combination of cytokines, growth factors, and immune molecules that reflect their unique microenvironment. Therefore, DBMSCs could be attractive, alternative candidates for MSC-based therapies that treat diseases associated with inflammation and oxidative stress.

Public awareness of blood donation in Central Saudi Arabia

Introduction In Saudi Arabia, voluntary donors are the only source of blood donation. The aim of this study was to assess the level of public knowledge and attitude toward blood donation in Saudi Arabia. Methods Using a previously validated questionnaire that comprises 38 questions to assess the levels of knowledge, attitudes, and motivations towards blood donation, 469 Saudi adults who attended different shopping malls in Riyadh, Saudi Arabia were surveyed. Multiple regression analyses were used to identify the significant predictors of blood donation, with the significance set at P<0.05. Results Approximately half of all subjects (53.3%) reported that they had previously donated blood, 39% of whom had donated more than once. The knowledge percentage mean score was 58.07%, denoting a poor level of knowledge, with only 11.9% reporting a good level of knowledge. The attitude percentage mean score towards donation was 75.45%, reflecting a neutral attitude towards donating blood, with 31.6% reporting a positive attitude. Donation was significantly more prevalent among males than females (66% versus 13.3%; P<0.001). After adjustment for confounders, a higher knowledge score (t=2.59; P=0.01), a higher attitude score (t=3.26; P=0.001), and male sex (t=10.45; P<0.001) were significant predictors of blood donation. An inability to reach the blood donation centers and a fear of anemia were the main reasons for females not donating blood (49.9% and 35.7%, respectively), whereas a lack of time was the main reason for males (59.5%). Conclusion Prevalence of blood donation was less than satisfactory among the Saudi public, probably due to misconceptions, poor knowledge, and unfavorable attitude to donation. Educational programs are necessary to increase the level of knowledge and improve the attitude of the Saudi public toward blood donation. Providing mobile blood collection units nearer to individuals’ places of work to reduce their time costs of donating is a necessity.

Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells From Decidua Parietalis of Human Term Placenta

Mesenchymal stem/multipotent stromal cells (MSCs) from the human placenta show stem cell-like properties useful for regenerative medicine. Previously, we reported that MSCs isolated from the fetal part of human term placentae have characteristics, which make them a potential candidate for regenerative medicine. In this study, we characterized MSC isolated from the maternal part of human term placenta. The MSCs were isolated from the decidua parietalis (DPMSCs) of human placenta using a digestion method and characterized by colony-forming unit assay and the expression of MSC markers by flow cytometry technique. In addition, DPMSC differentiation into the 3 mesenchymal lineages was also performed. Moreover, the gene and protein expression profiles of DPMSCs were identified by real-time polymerase chain reaction and flow cytometry techniques, respectively. Furthermore, proteins secreted by DPMSCs were detected by sandwich enzyme-linked immunosorbent assays. Finally, the proliferation and migration potentials of DPMSCs were also determined. The DPMSCs were positive for MSC markers and negative for hematopoietic and endothelial markers, as well as costimulatory molecules and HLA-DR. Functionally, DPMSCs formed colonies and differentiated into chondrocytes, osteocytes, and adipocytes. In addition, they proliferated and migrated in response to different stimuli. Finally, they expressed and secreted many biological and immunological factors with multiple functions. Here, we carry out an extensive characterization of DPMSCs of human placenta. We report that these cells express and secrete a wide range of molecules with multiple functions, and therefore, we suggest that these cells could be an attractive candidate for cell-based therapy.

Health-related quality of life in patients with sickle cell disease in Saudi Arabia

BackgroundThere is a lack of research concerning health-related quality of life (HRQoL) in Saudi patients with sickle cell disease (SCD), particularly among adult populations. The aim of the current study was to describe the characteristics of SCD patients and their impact on their quality of life (QoL).MethodsSix hundred twenty-nine adult SCD patients who attended King Fahad Hospital in Hofuf and King Fahad Central Hospital in Jazan were included in the analysis. Demographic/clinical data were collected and an Arabic version of the Medical Outcomes 36-Item Short-Form Health Survey (SF-36) questionnaire was used to assess QoL.ResultsSCD patients who hold a university degree reported positive impacts on the following domains of SF-36: physical role function, vitality, emotional well being, social function, pain reduction, and general health (P = .002, P = .001, P = .001, P = .003, P = .004, and P = .001, respectively). In general, patients with fever, skin redness, swelling, or history of blood transfusion tended to impair the health status of the SF-36. A multivariate analysis revealed that patients with a university degree tended to report high scores of physical role functions, emotional role function, and vitality. Patients with regular exercise tend to increase vitality, social function, general health, and reduce pain. Unemployment tends to lessen vitality and worsen pain. On average, pain, social function, and physical function scores tended to worsen in patients with swelling or history of blood transfusion.ConclusionsThis study highlighted that poor education, fever, skin redness, and swelling were negatively associated with specific components of SF-36. SCD patients with a history of blood transfusion found their QoL poorer, whereas regular exercise tended to improve QoL.

Improving cord blood unit quantity and quality at King Abdullah International Medical Research Center Cord Blood Bank.

Public cord blood banks (CBBs) store cord blood unit (CBU) donations for anyone in need. However, strict regulations need to be followed to build up high‐quality bank products that can be used worldwide. We established a public CBB at a tertiary hospital in Saudi Arabia. Here, we investigated the reasons behind rejecting or not collecting CBUs over 2 years (2011‐2012) and which steps were implemented to improve the number and quality of storable units.

Preconditioning by Hydrogen Peroxide Enhances Multiple Properties of Human Decidua Basalis Mesenchymal Stem/Multipotent Stromal Cells

Stem cell-based therapies rely on stem cell ability to repair in an oxidative stress environment. Preconditioning of mesenchymal stem cells (MSCs) to a stress environment has beneficial effects on their ability to repair injured tissues. We previously reported that MSCs from the decidua basalis (DBMSCs) of human placenta have many important cellular functions that make them potentially useful for cell-based therapies. Here, we studied the effect of DBMSC preconditioning to a stress environment. DBMSCs were exposed to various concentrations of hydrogen peroxide (H2O2), and their functions were then assessed. DBMSC expression of immune molecules after preconditioning was also determined. DBMSC preconditioning with H2O2 enhanced their proliferation, colonogenicity, adhesion, and migration. In addition, DBMSCs regardless of H2O2 treatment displayed antiangiogenic activity. H2O2 preconditioning also increased DBMSC expression of genes that promote cellular functions and decreased the expression of genes, which have opposite effect on their functions. Preconditioning also reduced DBMSC expression of IL-1β, but had no effects on the expression of other immune molecules that promote proliferation, adhesion, and migration. These data show that DBMSCs resist a toxic environment, which adds to their potential as a candidate stem cell type for treating various diseases in hostile environments.

Depression and anxiety in patients with hematological malignancies, prevalence, and associated factors

Objectives: To study the prevalence and associated factors of depression and anxiety in hematological cancers (HC) patients. Methods: We conducted a cross-sectional survey in all HC patients at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia between March 2014 and June 2015. We excluded patients with depression, or generalized anxiety disorder. We conducted a structured face to face interview using an internally developed and validated questionnaire (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 patient’s questionnaire with all participants). Results: Among 211 participants, depression was detected in 98 (46.5%) and anxiety was detected in 47 (22.3%). Thirty-eight (18.1%) had concurrent anxiety and depression. Multiple co-morbidities and tense home atmosphere were predictive for anxiety and depression. We found no association between gender, smoking, income, or being on active therapy and depression or anxiety. Conclusions: Depression and anxiety are highly prevalent in HC patients in KAMC. Health care providers should screen HC cancers for depression and anxiety; as early intervention possibly improve their disease outcome and will likely enhance their psychological wellbeing.

Appendicitis and intestinal infarction due to aspergillosis in a patient with acute myeloid leukemia

Small bowel infarction is a rare and fatal complication of invasive aspergillosis following chemotherapy in acute myeloid leukemia (AML) patients. We describe a case of an adult patient with an AML who developed appendicitis and intestinal infarction secondary to aspergillosis following anti-leukemic chemotherapy. The diagnosis was made histologically at laparotomy. The patient died later despite antifungal therapy.