Favorable outcome of non-myeloablative allogeneic transplantation in adult patients with severe sickle cell disease: A single center experience of 200 patients.

Allogeneic hematopoietic stem cell transplant (HSCT) for adults with severe sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. Herein, we are reporting our long-term outcome data of non-myeloablative (NMA) HSCT in adults with severe SCD with emphasis on factors predicting event free survival (EFS). Adults with severe SCD undergoing NMA match-related donor allogeneic HSCT from 2015 to 2021 with at least 12 months of follow-up were included. A total of 200 patients were included with a median age of 26 years (14-43) and 56% were male. The median infused CD34 dose was 13.7 (5.07-25.8), respectively. Median absolute neutrophil count engraftment was 19 (13-39) days with 51% of patients receiving GCSF to expedite recovery. A total of 17 patients experienced GF; 3 as primary and 14 as secondary within a median time of 204 days (40-905). A 76% successfully discontinued sirolimus at the last follow-up. Median follow-up for the cohort is 29.2 (2.1-71.4) months. Estimated 3-year EFS and OS were 88.2% (81.9-92.5) and 94.6% (89.2-97.3). At multivariable analysis, minor ABC incompatibility hazard ratio (HR) 4 (1.3-12.1; 0.014) and allo-antibody against non-ABO donor antigens HR 4.3 (1.3-14.1; 0.016) were significant for EFS. No clonal evolution or myeloid malignancies were seen. This largest single-center report of NMA HSCT in adults with severe SCD further delineated its feasibility, potential toxicities, and fertility outcomes. GF remains a major impediment and appears dependent on ABO matching and non-ABO antibodies.

Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality.

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population. We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01-2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16-4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype (P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.

Chemotherapy-Induced Peripheral Neuropathy and its Impact on Health-Related Quality of Life among Multiple Myeloma Patients: A Single-Center Experience.

AIM: Chemotherapy-induced peripheral neuropathy (CIPN) is a long-term neurological health issue in patients diagnosed with multiple myeloma (MM). The aim of this study was to assess CIPN symptoms and health-related quality of life (HRQOL) among MM patients. METHODS: A cross-sectional survey was conducted among patients diagnosed with MM in a tertiary care hospital using a self-reported Arabic questionnaire, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire for CIPN scale (QLQ-CIPN20). The HRQOL was assessed using EORTC multiple myeloma module (QLQ-MY20). Categorical variables were reported in frequency tables and percentages. Age and duration of MM diagnosis were reported as mean and standard deviation. Survey responses were presented using descriptive statistics. RESULTS: In total, 62 patients had participated. Males were 60%. The average age was 58.74 ± 11.49 years. On sensory scale, 20% reported "quite a bit"/"very much" tingling in fingers/hands, 23% in toes/feet, 39% numbness in fingers/hands, 37% in toes/feet, and 43% reported trouble standing or walking. On motor scale, 40% reported trouble walking and 60% had difficulty in climbing stairs/standing up from chair. On autonomic scale, 27% reported orthostatic hypotension and only 13/37 (46%) males reported erectile dysfunction. For HRQOL, 50% reported bone aches/pain, 42% reported back pain, 57% reported feeling ill, 33% reported lost hair, 35% had been thinking about their illness, whereas 28% were worried about future health and 22% had reported being worried about dying. CONCLUSION: MM patients encounter CIPN symptoms with impaired HRQOL. Capturing CIPN as a patient-reported outcome needs to be considered in routine clinical practice.

CD95-mediated apoptosis in Burkitt's lymphoma B-cells is associated with Pim-1 down-regulation.

B-cells of the high-grade non-Hodgkin lymphoma Burkitt's lymphoma (BL) overexpress survival oncoproteins, including the proviral integration site for Moloney murine leukaemia virus kinase (Pim)-1, and become apoptosis resistant. Activated death receptor CD95 after ligation with anti-CD95 monoclonal antibody (mAb) resulted in the regression of BL via induction of apoptosis, suggesting a decrease of survival protein expression. Here, CD95-mediated apoptotic pathways in BL B-cell lines (Raji and Daudi) following treatment with anti-CD95 mAb was investigated with the cause-and-effects on pim-1 gene expression, in comparison with leukemic cell line (K562) used as CD95-negative cells. Immunohistochemical staining for CD95 and Pim-1 was performed, and the effects of anti-CD95 mAb on apoptotic signalling using western blotting, on caspase activity and cell survival of BL B-cell and leukemic cell lines were determined. We showed that Raji cells expressed more CD95 receptors than Daudi cells. Half of each population underwent apoptosis accompanied by decreased cell viability after anti-CD95 mAb treatment. Distinct extrinsic and intrinsic CD95-mediated apoptotic pathways in Raji and Daudi cells were revealed by high caspase activity and mitochondrial outer membrane permeabilization, respectively. We observed decreased Pim-1 transcript and protein expression levels with increased heat-shock protein (Hsp)70 and decreased Hsp90 expression in anti-CD95 mAb-treated cells. Throughout the study, K562 cells did not undergo apoptosis upon anti-CD95 mAb treatment. Pim-1 knockdown following to stable transfection with plasmid vectors induced apoptosis and decreased viability of BL and K562 cells. Therefore, CD95-mediated apoptosis induces Pim-1 down-regulation in BL B-cells, but Pim-1 down-regulation cannot fully eradicate BL and leukaemia.

Predictors of patient satisfaction in an emergency care centre in central Saudi Arabia: a prospective study.

AIM: This study aimed to (i) assess the level of patient satisfaction and its association with different sociodemographic and healthcare characteristics in an emergency care centre (ECC) in Saudi Arabia and (ii) to identify the predictors of patients' satisfaction. METHODS: A prospective cohort study of 390 adult patients with Canadian triage category III and IV who visited ECC at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between 1 July and end of September 2011 was conducted. All patients were followed up from the time of arrival at the front desk of ECC until being seen by a doctor, and were then interviewed. Patient satisfaction was measured using a previously validated interview-questionnaire, within two domains: clarity of medical information and relationship with staff. Patient perception of health status after as compared with before the visit, and overall life satisfaction were also measured. Data on patient characteristics and healthcare characteristics were collected. Multiple linear regression analysis was used, and significance was considered at p≤0.05. RESULTS: One-third (32.8%) of patients showed high level of overall satisfaction and 26.7% were unsatisfied, with percentage mean score of 70.36% (17.40), reflecting moderate satisfaction. After adjusting for all potential confounders, lower satisfaction with the ED visit was significantly associated with male gender (p<0.001), long waiting time (p=0.032) and low perceived health status compared with status at admission (p<0.001). Overall life satisfaction was not a significant predictor of patient satisfaction. CONCLUSIONS: An appreciation of waiting time as the only significant modifiable risk factor of patient satisfaction is essential to improve the healthcare services, especially at emergency settings.

Saudi SCD patients' symptoms and quality of life relative to the number of ED visits.

BACKGROUND: Individuals living with sickle cell disease (SCD) have significantly increased emergency department (ED) use compared to the general population. In Saudi Arabia, health care is free for all individuals and therefore has no bearing on increased ED visits. However, little is known about the relationship between quality of life (QoL) and frequency of acute care utilization in this patient population. METHODS: A cross-sectional study was conducted on 366 patients with SCD who attended the outpatient department at King Fahad Hospital, Hofuf, Saudi Arabia. Data were collected through self-administered surveys, which included: demographics, SCD-related ED visits, clinical issues, and QoL levels. We assessed the ED use by asking for the number of SCD-related ED visits within a 6-month period. RESULTS: The self-report survey of ED visits was completed by 308 SCD patients. The median number of SCD-related ED visits within a 6-month time period (IQR) was four (2-7 visits). According to the unadjusted negative binomial model, the rate of SCD-related ED visits increased by (46, 39.3, 40, and 53.5 %) for patients with fever, skin redness with itching, swelling, and blood transfusion, respectively. Poor QoL tends to increase the rate of SCD-related ED visits. Well education and poor general health positively influenced the rate of SCD-related ED visits. Well education tends to increase the rate of SCD-related ED visits by 50.2 %. The rate of SCD-related ED visits decreased by 1.4 % for every point increase in general health. CONCLUSION: Saudi patients with sickle cell disease reported a wide range of SCD-related ED visits. It was estimated that six of 10 SCD patients had at least three ED visits within a 6-month period. Well education and poor general health resulted in an increase in the rate of SCD-related ED visits.

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

BACKGROUND: There 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). METHODS: Six 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. RESULTS: SCD 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. CONCLUSIONS: This 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.

Using the health belief model to predict breast self examination among Saudi women.

BACKGROUND: In the Kingdom of Saudi Arabia, breast cancer (BC) usually presents at advanced stages and more frequently in young pre-menopausal women in comparison to western countries. There is controversy surrounding the efficacy of breast self examination (BSE) for early detection of BC in countries where other methods are available. This study aims to explore the perception towards breast cancer and towards BSE among Saudi women, using the Health Belief Model (HBM). METHODS: A convenient sample of adult Saudi female employees, working at King Abdulaziz Medical City, Riyadh, Saudi Arabia (n = 225), and their non-working adult female family members (n = 208), were subjected to the Arabic version of revised Champion's Health Belief Model Scale (CHBMS) and the Arabic version of Breast Cancer Awareness Measure (CAM), to assess their knowledge and attitude on BC respectively. Percentage mean score (PMS) for each HBM domain was calculated. Significant predictors of BSE practice were identified using logistic regression analysis and significance was considered at p < 0.05. RESULTS: The majority of women heard about BSE (91.2 %), only 41.6 % reported ever practicing BSE and 21 % performed it regularly. Reported reasons for not doing BSE were: not knowing how to examine their breast (54.9 %), or untrusting themselves able to do it (24.5 %). Women were less knowledgeable about BC in general, its risk factors, warning signs, nature and screening measures (PMS:54.2 %, 44.5 %, 61.4 %, 53.2 %, 57.6 % respectively). They reported low scores of; perceived susceptibility, seriousness, confidence and barriers (PMS: 44.8 %, 55.6 %, 56.5 % & 41.7 % respectively), and high scores of perceived benefits and motivation (PMS: 73 % & 73.2 % respectively) to perform BSE. Significant predictors of BSE performance were: levels of perceived barriers (p = 0.046) and perceived confidence (p = 0.001) to BSE, overall knowledge on BC (p < 0.001), work status (p = 0.032) and family history of BC (p = 0.011). CONCLUSIONS: Saudi women had poor knowledge on BC, reported negative attitude towards BSE and their practice was poor. Working women and those with family history of BC, higher perceived confidence and lower perceived barriers on HBM, and those with high level of knowledge on BC were more likely to perform BSE. Breast awareness as an alternative to BSE needs further investigations. HBM was shown as a valid tool to predict BSE practice among Saudi women.

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

BACKGROUND: 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. STUDY DESIGN AND METHODS: A total of 2891 mothers were evaluated. Reasons for rejecting donors, not collecting, and rejecting units before or after collection were analyzed and compared for the years 2011 and 2012. RESULTS: A total of 1157 (40%) CBUs were not collected, mainly due to staff availability, and 564 (20%) CBUs were rejected. The main reason for rejecting donations was the mother's or neonate's health. Rejecting CBUs after collection was due to low volume. A total of 1170 (40%) CBUs were successfully collected for potential banking and sent for processing; however, 58% were rejected in the laboratory due to low total nucleated cell counts. Several changes were implemented during the 2 years including physician education and awareness, in utero collection, cesarean collection, and staff recruitment. These changes positively affected the numbers of our collected units. Out of the initially eligible mothers in 2011, only 17% were banked; this was increased to 33% in 2012. CONCLUSIONS: We identified the problems with collecting CBUs for banking and will keep improving our selection process of recruiting more CBUs of high quality.

In vitro cytotoxicity of Artemisia vulgaris L. essential oil is mediated by a mitochondria-dependent apoptosis in HL-60 leukemic cell line.

BACKGROUND: The essential oil (EO) of Artemisia vulgaris L. has been traditionally used worldwide for treating a large number of diseases. Although major components in A. vulgaris EO have been shown to inhibit growth of different cancer cells, as pure compounds or part of other plants extracted oil, no information is known about its anti-proliferative activities. Therefore, the current investigation has evaluated the toxicity of the plant extracted oil from buds (AVO-b) and leaves (AVO-l) and characterized their growth inhibitory effects on cancer cells. METHODS: AVO-b and AVO-l from A. vulgaris L. were extracted by hydrodistillation, and their effect on the viability of human HL-60 promyelocytic leukemia and various other cancer cell lines was tested using MTT assay. Flow cytometric analysis of apoptosis, DNA fragmentation assay, caspases enzymatic activities and Western blotting were used to determine the apoptotic pathway triggered by their action on HL-60 cells. RESULTS: Low concentrations of AVO-b and AVO-l inhibited the growth of HL-60 cells in a dose- and time-dependent manner. Employing flow cytometric, DNA fragmentation and caspase activation analyses, demonstrated that the cytotoxic effect of the oils is mediated by a caspase-dependent apoptosis. Kinetic studies in the presence and absence specific caspase inhibitors showed that activation of caspase-8 was dependent and subsequent to the activation of caspases-9 and -3. In addition, the essential oil caused a disruption of the mitochondrial transmembrane potential (ΔΨm), increased the release of cytochrome c to the cytosol, and altered the expression of certain members of Bcl-2 family (Bcl-2, Bax and Bid), Apaf-1 and XIAP. Interestingly, low doses of AVO-b and AVO-1 also induced apoptosis in various cancer cell lines, but not in noncancerous cells. CONCLUSIONS: The results demonstrate that the EO-induced apoptosis in HL-60 cells is mediated by caspase-dependent pathways, involving caspases-3, -9, and -8, which are initiated by Bcl-2/Bax/Bid-dependent loss of ΔΨm leading to release of cytochrome c to the cytoplasm to activate the caspase cascade. The finding that AVO-b and AVO-l are more efficient to induce apoptosis in different cancer cell lines than noncancerous cells, suggests that A. vulgaris might be a promising source for new anticancer agents.