Prognostics and Clinical Outcomes in Patients Diagnosed With Acute Lymphoblastic Leukemia in King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

Background Acute lymphoblastic leukemia (ALL) is a hematological cancer that causes an accumulation of immature cells in the bone marrow. The count of white blood cells (WBCs) is an independent predictor of survival. Integrating first-line treatment, such as intensive chemotherapy, with prognostic factors aids in developing critical therapeutic decisions and improving long-term outcomes. This study evaluated several prognostics such as age, WBCs, ALL cell subtypes, and absolute WBC counts. Methods This study involved a retrospective record review and was conducted by scanning the medical records of all individuals who developed ALL and were on chemotherapy at a teaching Hospital in Jeddah between 2012 and 2018. The data entry was done using Microsoft Excel, while the analysis was done using SPSS Version 21. To test any associations, frequency and measure of central tendencies, t-test, and chi-square test were used. Results A total of 98 of ALL patients were on chemotherapy, and 18 were excluded. Thus, 80 patients were analyzed. The mean age for all patients was 13.6 years (range: 0.6-26.6 years), and the most frequent ages were less than 18 years (90%). More than half of them (62.5%) were males. The majority of the patients were Bangladeshi, Pakistani, Indian, Afghan, Indonesian, and Myanmar (37.7%), and the least were Saudi (3.8%). B subtype (75.9%) was more common than T subtype (24.1%). The first remission after treatment was in 66 patients, with a mean of 6.86 years. There was a significant adverse relationship between the ability of patients to reach the first remission and WBC count (p = 0.032). There was strong significant negative correlation between absolute lymphocyte count (ALC) and survival duration after treatment (r = -0.669; p = 0.012). Conclusions The impact regarding age and WBC is almost like most previous studies. ALC shows a strong poor prognosis, while ALL cell subtypes demonstrate a contradictory prognosis effect.

Immunogenicity of The BNT162b2 COVID-19 mRNA and ChAdOx1 nCoV-19 Vaccines in Patients with Hemoglobinopathies.

INTRODUCTION: Studies assessing immune responses following Pfizer-BioNTech BNT162b2 mRNA COVID-19 (Pfizer) and ChAdOx1 nCoV-19 AZD1222 (AstraZeneca) vaccines in patients with hemoglobinopathy are non-existent in the literature despite being thought at high risk of infection. METHODS: Prospectively, we collected serum from patients with hemoglobinopathies at least 14 days post vaccine and measured neutralizing antibodies (nAb) in addition to binding antibodies using in-house assays. RESULTS: All 66 participants mounted a significant binding antibody response (100%), but nAbs were detected in (56/66) post-vaccine with a rate of 84.5%. Age, gender, vaccine type, spleen status, hydroxyurea use, and hyperferritinemia did not affect the rate significantly. While 23/32 (71.8%) patients receiving only one dose of the vaccine were able to mount a positive response, 33/34 (97.05%) of those who had two doses of any vaccine type had a significant nAbs response. Patients who had anti-nucleocapsid (N), signifying asymptomatic infection in the past, were able to produce nAbs (31/31). No nAbs were detected in 10/35 (28.5%) patients with no anti-N antibodies. CONCLUSION: Our results provide supportive data when advising patients with hemoglobinopathy to receive COVID-19 vaccines and ensure booster doses are available for better immunity. Whenever available, measurement of nAb is recommended.

Low clinical utility of testing for anti-platelet factor 4 in asymptomatic individuals after ChAdOx1 nCoV-19 vaccine.

INTRODUCTION: The development of anti-platelet factor 4 (PF4) antibodies is linked to a rare thrombotic complication described now as vaccine-induced immune thrombotic thrombocytopenia (VITT). This clinical syndrome with thrombosis and thrombocytopenia was reported after exposure to the Oxford-AstraZeneca COVID-19 vaccine, ChAdOx1 nCoV-19 vaccine (AZD1222), and Ad26.COV2.S vaccine (Janssen/Johnson & Johnson). In the absence of the clinical features, the incidence of positive anti-PF4 antibodies in asymptomatic individuals post-vaccination is unclear. METHODS: The aim of this study was to evaluate the development of anti-PF4 antibodies in asymptomatic individuals 14-21 days after receiving the first dose of ChAdOx1 nCoV-19 vaccine (AZD1222) and BNT162b2 vaccine. Prospectively, we collected serum from individuals before and after ChAdOx1 nCoV-19 vaccine and BNT162b2 vaccine and measured anti-PF4 antibodies using the Asserachrom HPIA IgG ELISA (Stago, Asnieres, France). RESULTS: We detected positive anti-PF4 antibodies in 5 of 94 asymptomatic individuals post-vaccine with a rate of 5.3% with low titers (OD 0.3-0.7). Four of 5 individuals who tested positive after the vaccine had also positive anti-PF4 antibodies before the vaccine, which indicates that a majority of the positive results are due to preexisting anti-PF4 antibodies. We did not find a relation between the development of anti-PF4 antibodies and the immune response to the vaccine, status of prior COVID-19 infection, and baseline characteristics of participants. None of the participants developed thrombosis nor thrombocytopenia. CONCLUSION: Our results provide new evidence to guide the diagnostic algorithm of suspected cases of VITT. In the absence of thrombosis and thrombocytopenia, there is a low utility of testing for anti-PF4 antibodies.

Prognostics and Clinical Outcomes in Patients Diagnosed With Acute Myeloid Leukemia (AML) in a Teaching Hospital.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis and survival depend on several factors that determine tumor behavior and response to therapy. AML has a poor prognosis that depends on several factors: patient's age, gender, body mass index (BMI), baseline white blood cells count, and bone marrow blast (BMB) cell count at the time of diagnosis. Therefore, this study aimed to determine the prognostic role of these factors and their impact on outcomes, and how these prognostic factors may affect AML patients before and after induction chemotherapy. METHODS: The study design is an observational, retrospective record review. We included records of patients diagnosed with primary and secondary AML who received chemotherapy between 2013 and 2019 at King Abdulaziz University in Jeddah, Saudi Arabia. Data were extracted from medical records, entered into an Excel sheet (Microsoft Corp., Redmond, WA), and analyzed using SPSS Statistics, version 25 (IBM Corp., Armonk, NY). RESULTS: Forty-two AML patients who were started on chemotherapy were analyzed. The mean age at diagnosis was 35 ± 22.2 years; 52.4% were male. The ability to achieve the first remission varied according to age group; the 21-45 age group had the higher ability and survival rate of 75.0%. On the other hand, the mortality incidence was higher (at 70.0%) in both the 11-20 and the 46-70 age groups. A strong negative correlation was observed between age and survival duration after treatment (SDAT) (r = - 0.618, p = 0.004). The death incidence was increased in the BMI ranges that were under and above the normal weight range. SDAT differed significantly between the three groups in favor of the normal-weight patients (p = 0.019). We found that patients with BMB < 5 had the most deaths. There was a significant negative association between BMB and days to achieve the first remission after treatment (p = 0.033).  Conclusion: Age, BMI, and BMB are considered effective prognostic factors for AML patients.

Mutations Encountered in Acute Lymphoblastic Leukemia: A Retrospective Study in a Teaching Hospital in Jeddah, Saudi Arabia.

Background Acute lymphoblastic leukemia (ALL) is an invasive cancer that results from the malignant conversion and rapid replication of white blood cells and hematopoietic stem cells that supply multiple lymphocytes. Harmful gene mutations occur in more than two-thirds of patients with ALL; however, these mutations have not been extensively identified in Saudi Arabia. Aim The aim of this study was to identify the types of mutations in patients with ALL at King Abdulaziz University Hospital (KAUH) in Jeddah. In addition, we identified the most common mutations. Methods A retrospective study was performed on patients who were diagnosed with ALL from January 2009 to January 2019 at the Department of Hematology at KAUH. Our target population comprised patients diagnosed with ALL, including all age groups and both sexes. Patients were excluded if they had Down syndrome or central nervous system involvement, Li-Fraumeni syndrome, or neurofibromatosis. Results Of the 130 patients with ALL, 101 (77.77%) were children. The number of men (n=81) was substantially more than that of women (n=49). The data showed that 13.1% of our patients had mutations, and they occurred more frequently in patients with B-cell lymphoblastic ALL (B-ALL) than in those with T-cell lymphoblastic ALL (T-ALL). Several mutations, including BCR-ABL and ETV6/RUNX1, were more common in B-ALL, whereas the MLL-F0X04mutation was more commonly observed in T-ALL. There was a significant difference between the types of ALL and the genes involved (p=0.039). One female patient had translocation t(X;11)(q26;q23) (MLL-F0X04), which is a rare mutation. Conclusion In summary, 13.1% of our study population had mutations. The BCR-ABL fusion gene was the most frequent mutation in patients at KAUH, and it occurred at a higher rate in B-ALL. Moreover, we detected other mutations, such as ETV6/RUNX1 and MLL-F0X04. The gene mutations were significantly different between B-ALL and T-ALL.

A Novel Nanoformulation of Ellagic Acid is Promising in Restoring Oxidative Homeostasis in Rat Brains with Alzheimer's Disease.

BACKGROUND: Aluminum toxicity induces neurodegenerative changes in the brain and results in Alzheimer's disease (AD). OBJECTIVE: Here, the aim was to evaluate the antioxidant therapeutic effects of ellagic acid (EA) and EA-loaded nanoparticles (EA-NP) in an aluminum chloride-induced AD rat model. METHODS: The nanoparticles' loading of EA was 0.84/1 w/w. The in vitro release kinetics of EA from EA-NP in fetal bovine serum showed 60% release in the first 1-5 hours, followed by sustained release at 60-70% over 6-24 hours. Six groups were implemented; group 1 served as the control, group 2 received EA, group 3 received EA-NP, group 4 was the AD rat model administered AlCl3 (50 mg/kg) for 4 weeks, groups 5 (AD+EA) and 6 (AD+EA-NP) were treated with EA and EA-NP, respectively, for 2 weeks after AlCl3 was stopped. The neurotoxicity in the rat brain was examined by measuring the brain antioxidant biomarkers catalase, glutathione, and total antioxidant activity and lipid peroxidation (thiobarbituric acid, TBA). Histopathological studies using hematoxylin and eosin, cresyl violet, silver stains, and the novel object recognition test were examined. RESULTS: Data revealed significant increase of antioxidant biomarkers and decreased TBA in the EA-NP group. The pathological hallmarks of AD-vacuolation of the neurons, chromatolysis, neurofibrillary tangles, and the senile plaques in brains of the AD rat model were decreased and restoration of Nissl granules was noted. The calculated discrimination index in the behavioral test increased more in cases treated with EA-NP. CONCLUSION: The treatment of AD with EA-NP was more effective than EA in alleviating the oxidative neurotoxic effects on AD rat brains.

Untargeted Metabolomics Identifies Key Metabolic Pathways Altered by Thymoquinone in Leukemic Cancer Cells.

Thymoquinone (TQ), a naturally occurring anticancer compound extracted from Nigella sativa oil, has been extensively reported to possess potent anti-cancer properties. Experimental studies showed the anti-proliferative, pro-apoptotic, and anti-metastatic effects of TQ on different cancer cells. One of the possible mechanisms underlying these effects includes alteration in key metabolic pathways that are critical for cancer cell survival. However, an extensive landscape of the metabolites altered by TQ in cancer cells remains elusive. Here, we performed an untargeted metabolomics study using leukemic cancer cell lines during treatment with TQ and found alteration in approximately 335 metabolites. Pathway analysis showed alteration in key metabolic pathways like TCA cycle, amino acid metabolism, sphingolipid metabolism and nucleotide metabolism, which are critical for leukemic cell survival and death. We found a dramatic increase in metabolites like thymine glycol in TQ-treated cancer cells, a metabolite known to induce DNA damage and apoptosis. Similarly, we observed a sharp decline in cellular guanine levels, important for leukemic cancer cell survival. Overall, we provided an extensive metabolic landscape of leukemic cancer cells and identified the key metabolites and pathways altered, which could be critical and responsible for the anti-proliferative function of TQ.

Consensus Statement by an Expert Panel on the Diagnosis and Management of Iron Deficiency Anemia in the Gulf Cooperation Council Countries.

BACKGROUND: Iron deficiency (ID) and ID anemia (IDA) are common in the member states of the Gulf Cooperation Council (GCC). The unique genetic and lifestyle factors of the patient population in the region have necessitated the development of recommendations to help educate health-care professionals on appropriate diagnosis and management of ID/IDA. METHODS: A panel of regional experts, including gastroenterologists and hematologists with expertise in the treatment of IDA, was convened to develop regional practice recommendations for ID/IDA. After reviewing the regional and international literature, the expert panel developed consensus recommendations for screening, diagnosis, and treatment of patients with IDA in the GCC region. RESULTS: The recommendations proposed were customized to the patient population keeping in view the increasingly recognized burden of coeliac disease, high fertility and obesity rates, high prevalence of alpha- and beta-thalassemia traits, and poor tolerance and low treatment compliance with oral iron therapy. CONCLUSIONS: This consensus statement proposes recommendations for screening, diagnosis, and treatment of IDA in the GCC region.

Knowledge and attitude toward hemoglobinopathies premarital screening program among unmarried population in western Saudi Arabia.

OBJECTIVES: To assess the knowledge and attitude toward hemoglobinopathies premarital screening (PMS) program among unmarried population in Jeddah, Kingdom of Saudi Arabia. METHODS: A cross-sectional study was conducted among 1039 unmarried males and females from the general population who fulfilled the eligibility criteria. Data was collected from July-December 2017, using an electronic questionnaire to assess the socio-demographic data, knowledge and attitudes of the participants regarding PMS. Results: Approximately half of the participants had poor knowledge scores (51.1%), while 28.4% of them had fair and 20.5% had good scores. Individuals with an educational level of "university degree and above" had significantly higher knowledge than  those with lower educational levels. Furthermore, 60.4% of the participants had a positive attitude toward PMS. The data was analyzed using the Statistical Package for the Social Sciences (SPSS) Version 21 (IBM Corp., Armonk, NY, USA); and a Chi-squared test was used for comparisons between proportions and a p-value ≤0.05 was considered significant. Conclusion: Participants showed a lack of knowledge regarding PMS but they had a positive attitude towards the program. More efforts are required to raise awareness in the public regarding PMS, via social media and educational lectures in schools and universities. Additionally, early genetic screening may help improve test acceptance and higher impact.

Antimicrobial effect of different types of honey on Staphylococcus aureus.

Honey exhibits antimicrobial activities against a wide range of bacteria in different milieu. This study aims to compare the effects of five types of honey (both imported and local Saudi honey) against Staphylococcus aureus. The five types of honey (Manuka Honey UMF +20, Manuka Honey UMF +16, Active +10 Manuka Honey, Sidr honey and Nigella sativa honey) were evaluated for their bactericidal/bacteriostatic activities against both methicillin resistant and sensitive S. aureus. The inhibitory effect of honey on bacterial growth was evident at concentrations of 20% and 10% (v/v). Manuka Honey showed the best results. Manuka Honey UMF +20 had a bactericidal effect on both methicillin resistant and sensitive S. aureus. However, Sidr and N. sativa honey exerted only a bacteriostatic effect. The efficacy of different types of honey against S. aureus was dependent on the type of honey and the concentration at which it was administered. Manuka Honey had the best bactericidal activity. Future experiments should be conducted to evaluate the effects of honey on bacterial resistance.

The effect of wet cupping on quality of life of adult patients with chronic medical conditions in King Abdulaziz University Hospital.

OBJECTIVES: To assess the effect of wet cupping on health-related quality of life (HRQOL) of adult patients with chronic medical conditions, who were referred to the Cupping Clinic of King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia. Methods: A controlled, quasi-experimental study design was carried out among 629 patients referred for cupping from the KAUH Specialty Clinics, during the period from January to December 2014. Patients in the intervention group (309 patients) completed a pre-test included WHO quality of life-BREF, received one wet-cupping session, and filled-out the post-test (1 month later). Patients in the control group (320 patients) completed the pre-test during their enrollment in the study and post-test one month later. Both groups received their ordinary treatment. Descriptive and inferential statistics were performed.  Results: Pain was the most common cause for cupping referral. After cupping intervention, the mean scores of most of the HRQOL domains, especially the physical domain, improved significantly among patients in the intervention group. The mean total score of physical HRQOL domain was 61.6 ± 13.6 before cupping, and reached 69.7 ± 12.6 after intervention (paired t-test=11.3, p=0.000). Improvements in HRQOL were noticed for almost all types of pain and other medical conditions.  Conclusion: There are promising effects in favor of using wet cupping for improving HRQOL of patients with chronic conditions. Cupping is recommended as a complementary treatment modality for chronic medical conditions, especially pain.

Deviating from safety guidelines during deferiprone therapy in clinical practice may not be associated with higher risk of agranulocytosis.

BACKGROUND: A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5 × 10(9)/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real-life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis. PROCEDURE: This non-interventional surveillance program assessed the monitoring of deferiprone therapy in clinical practice. A total of 294 patients with transfusion-dependent anemias received deferiprone, as monotherapy or with another chelator, for up to 1 year. The participating physicians were not given any instructions about treatment and monitoring beyond being referred to the information in the package insert. RESULTS: ANC monitoring was conducted at an average interval of 5 ± 4 weeks, and deferiprone was not always interrupted upon detection of neutropenia. One patient (0.3%) experienced agranulocytosis, and nine others (3%) experienced a total of 11 episodes of neutropenia. All neutropenia episodes resolved; median time to resolution was similar whether or not treatment was interrupted; and no case of neutropenia progressed to agranulocytosis. CONCLUSIONS: These data indicate that less frequent ANC monitoring and continuation of deferiprone therapy during neutropenia are not associated with prolonged neutropenia or with progression to agranulocytosis.

Regional consensus opinion for the management of Beta thalassemia major in the Arabian Gulf area.

Thalassemia syndrome has diverse clinical presentations and a global spread that has far exceeded the classical Mediterranean basin where the mutations arose. The mutations that give rise to either alpha or beta thalassemia are numerous, resulting in a wide spectrum of clinical severity ranging from carrier state to life-threatening, inherited hemolytic anemia that requires regular blood transfusion. Beta thalassemia major constitutes a remarkable challenge to health care providers. The complications arising due to the anemia, transfusional iron overload, as well as other therapy-related complications add to the complexity of this condition. To produce this consensus opinion manuscript, a PubMed search was performed to gather evidence-based original articles, review articles, as well as published work reflecting the experience of physicians and scientists in the Arabian Gulf region in an effort to standardize the management protocol.

Flow cytometric assessment of leukocyte function in sickle cell anemia.

Sickle cell anemia is associated with susceptibility to infection due to hyposplenism and the reduced ability of neutrophils to kill pathogenic organisms. In this study, blood samples from sickle cell anemia patients were divided into two groups: the painful crisis group and the steady state group. Flow cytometric assessment of phagocytosis and burst formation of neutrophils and monocytes as well as basophil function were performed, and these were compared to those of age- and sex-matched normal control subjects. Neutrophils and monocytes in sickle cell anemia patients were significantly different from those in the normal control subjects in the areas of weaker phagocytosis, fewer ingested bacteria and reduced burst formation. Basophil degranulation was normal. This pilot study using flow cytometry explains in part the susceptibility to infection of sickle cell anemia patients despite their high neutrophil and monocyte counts.

Diagnosis and management of sickle cell disorders.

Sickle cell disease (SCD) is a wide-spread inherited hemolytic anemia that is due to a point mutation leading to a valine/glutamic acid substitution in the beta-globin chain, causing a spectrum of clinical manifestations in addition to hemolysis and anemia. Acute painful crisis is a common sequela that can cause significant morbidity and negatively impact the patient's quality of life. Remarkable improvements in our understanding of the pathogenesis of this clinical syndrome and the role of cell adhesion, inflammation, and coagulation in acute painful crisis have led to changes in the management of pain. Due to the endemic nature of SCD in various parts of the Middle East, a group of physicians and scientists from the United States and Middle East recently met to draw up a set of suggested guidelines for the management of acute painful crisis that are reflective of local and international experience. This chapter brings together a detailed etiology, pathophysiology, and clinical presentation of SCD, including the differential diagnoses of pain associated with the disease, with evidence-based recommendations for pain management and the potential impact of low-molecular weight heparin (LMWH), from the perspective of physicians and scientists with long-term experience in the management of a large number of SCD patients.

Pattern of HB F level rise during normal pregnancies.

Fetal hemoglobin (Hb F) is the normal hemoglobin (Hb) that is present in the fetus and usually almost absent in adults. The objective of this study was to assess the changes in Hb F levels during normal pregnancy. The level of Hb F was determined in serial blood samples from women at different stages of pregnancy using cation exchange high performance liquid chromatography (HPLC) and compared to age and sex-matched controls. A significant increase (p <0.001) was observed in the level of maternal Hb F; the mean Hb F level during pregnancy was 0.71 +/- 0.51%, while in the non pregnant control group it was 0.28 +/- 0.35%. There was no significant difference in Hb F levels in the three trimester groups using the ANOVA test (F = 0.25). Correlation studies between the gestational age and level of Hb F showed no significant increase of Hb F with advancing pregnancy (R = -0.053, p >0.05). The cause of the rise in Hb F is yet to be elucidated.

Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial.

A randomized double-blind clinical trial was performed to test the safety and efficacy of a low-molecular-weight heparin, tinzaparin (Innohep), for the management of acute painful vasoocclusive crisis characteristic of sickle cell anemia (SCA). We studied 253 patients with acute painful crisis but with no other complications of SCA, randomized to treatment or control groups. In the treatment group, 127 patients received tinzaparin at 175 IU/kg, subcutaneous once daily, along with supportive care including morphine analgesia; in the control group, 126 patients received placebo and the same supportive care. The maximal experimental treatment period was seven days. Analysis revealed a statistically significant reduction in number of days with the severest pain score, overall duration of painful crisis, and duration of hospitalization (p < 0.05 for each comparison of tinzaparin vs. placebo). The decline in pain intensity was sharper for tinzaparin-treated patients, and complications consisted of two minor bleeding events that were reported and treated by cessation of tinzaparin. This investigation demonstrated that tinzaparin, administered at its approved treatment regimen, reduced the severity and duration of acute crisis of SCA.

Recent advances in the diagnosis and treatment of deep vein thrombosis: a regional consensus.

Considerable progress has been made in the understanding of the risk factors for venous thromboembolism (VTE). The clinical applications of molecular techniques have allowed identification of important inherited, yet not uncommon, risk factors for VTE, such as mutations that cause Factor V Leiden and prothrombin G20210A. However, advances in our understanding have raised several questions regarding the need for, and duration of anticoagulation. At the end of the treatment period, low molecular weight heparins have become the drugs of choice and standard-of-care for VTE. In this review, cost effective diagnostic approaches for patients with suspected deep vein thrombosis, and recommended treatment options using evidence-based approaches, are described.