Bader Al Alwan

Sickle cell disease belongs to the hemoglobinopathies group that includes genetically inherited blood diseases. These diseases occurred due to single-gene autosomal recessive mutations. The inheritance of these mutations contributes to the formation of either abnormally structured hemoglobins or inadequate to no production of globin chains in the hemoglobins. Sickle cell disease constitutes a global concern since it can cause morbidity and early mortality of the affected people. It is a common monogenic disorder in Saudi Arabia where multiple organs are affected. The hepatobiliary system is among the affected systems with the spectrum of acute clinical presentations often referred to as “sickle cell hepatopathy”. The evaluation of liver enzymes as a sickle cell hepatopathy prediction tool is not fully addressed. Here in this work, we performed a retrospective correlation quantitative study to confirm that the decrease in the hemoglobin levels due to sickle cell crises predicts an early development of hepatomegaly. This prediction was estimated by correlating hemoglobin levels to the liver enzyme levels. The data was collected from King Abdulaziz Medical City in Riyadh for patients with a confirmed diagnosis of sickle cell disease for 5 years period and analyzed using SPSS and Microsoft excel. Our findings revealed an inverse relationship between hemoglobin levels and liver biomarkers. These results emphasize on the importance of earlier interventions to prevent liver degeneration in SCD patients.

Background and Objectives: Hydroxyurea (HU) is an effective medication used to reduce the frequency of painful crises associated with sickle cell disease (SCD). However, data describing its prevalence among SCD patients in the Eastern Region of Saudi Arabia are scarce. This is a multi-center, retrospective, cross-sectional study that aims to investigate the pattern of prescribing HU in SCD patients and to determine the association between prescribing HU and other co-prescribed medications used to manage SCD complications. Methods: Data were collected from patients who visited the hematology clinics of Al-Qatif Central Hospital (QCH) and King Fahad Hospital in Hofuf (KFHH) between June 2021 to May 2023. The data included demographics, prescribed medications, and recent laboratory test results, all of which were collected from patients’ medical records. Descriptive statistics were utilized to assess the difference between HU users vs. non-users. A binary logistic regression model was used to determine the association between prescribing HU and co-prescribed medications used to manage SCD complications. The results are presented as the odds ratio (OR) and 95% confidence interval (95% CI). Results: This study included 2816 SCD patients with a 56% prevalence of HU prescription. HU was prescribed for young age groups more often compared to old age group patients. Young males were more likely to be prescribed with HU compared to females, and it becomes dominant in females after the age of 36. HU users were more likely to have paracetamol (69% vs. 53%, OR = 1.9, 95% CI 1.6–2.2), NSAIDs (50% vs. 35%, OR = 1.7, 95% CI 1.5–2), and opioids (41% vs. 37%, OR = 1.3, 95% CI 1.1–1.6) co-prescribed, and less often to have laxatives (8% vs. 5%, OR = 0.66, 95% CI 0.48–0.9) and anticoagulants (22% vs. 15%, OR = 0.56, 95% CI 0.46–0.68) co-prescribed compared to non-users. Conclusions: The pattern of prescribing HU, supported by the association findings, raises concerns about patients’ compliance and adherence to HU therapy. Early health education, specifically to young female SCD patients, is warranted to increase the success rate of HU therapy.

Background/Objectives: Proton pump inhibitors (PPIs) are amongst the most commonly prescribed classes of medication. However, inappropriate PPI use can lead to several adverse drug reactions (ADRs). Limited data exist on factors contributing to the risk of ADRs associated with PPI prescribing patterns in the Eastern Region of Saudi Arabia. This retrospective, cross-sectional study aimed to assess the prevalence and the pattern of PPI use and to identify factors contributing to the risk of ADRs. Methods: Data were collected from electronic medical records of patients at Al-Qateef Central Hospital from January 2020 to December 2021. The inclusion criteria included patients aged ≥40 years attending an outpatient medical care clinic. PPI prescribing patterns were categorized based on their dosage intensity into low-dose, medium-dose (MD), and high-dose (HD) categories. Binary and multinominal logistic regression models were used to determine the relationship between PPI prescribing patterns and use, categorized by MD or HD, and patient characteristics, adjusted for significant covariates. Results are presented as adjusted odds ratio (OR) with corresponding 95% confidence intervals (95% CI). Results: The study included 41,084 patients. The prevalence of PPI prescribing was 31%. PPI users were more frequently found to be females than males (52% vs. 50%, p = 0.013); they were also likely to be prescribed more medications (7 vs. 6, p < 0.001), but less likely to have gastritis-related diseases (34% vs. 32%, p < 0.001) compared to non-users. PPI HD users were more likely male (56% vs. 43%, p < 0.001), older (53 vs. 52 years, p < 0.001), and prescribed more medications (11.8 vs. 2.8, p < 0.001) compared to MD users. PPI usage was associated with concurrent use of antiplatelet drugs (OR = 1.08, 95% CI 1.01–1.15). An increasing number of prescribed medications was associated with HD usage (OR = 1.13, 95% CI 1.12–1.14), but negatively associated with MD usage (OR = 0.7 95% CI 0.69–0.71). Female gender was negatively associated with HD usage (OR = 0.85, 95% CI 0.79–0.91). Conclusions: Our findings indicate that 31% of the included cohort were prescribed PPI. Inappropriate PPI prescribing related to the drug’s omission is a concern as PPI non-users presented with valid indications such as gastritis. Male gender and increasing NPM were the common factors contributing to increased risk of PPI ADR. This study points to the importance of re-evaluating PPI use to ensure effective therapy with minimum risks of ADR.

The repair and remodeling of injured tissues, known as wound healing, is a multifaceted process. The use of nanotechnology to speed up the healing process of wounds by promoting the right kind of mobility through different mechanisms has shown a lot of promise. Several nanotechnologies with novel properties have emerged in recent years, each of which targets a different issue associated with wound-healing processes. Through their antibacterial, anti-inflammatory, and angiogenic actions, nanomaterials may alter the wound microenvironment from a non-healing to a healing state. Wound dressings including hydrogels, gelatin sponges, films, and bandages may all benefit from the use of nanoparticles (NPs) to keep harmful microbes out. The addition of bioactive substances like antibiotics, NPs, and growth factors to certain dressings may further boost their efficacy. In conclusion, this review sheds light on wound healing that may be aided by the special features of materials based on nanotechnology. Although nanomaterials for wound healing show great promise, further study is needed before this promising area can convert its findings into consumer-friendly solutions.

Iron is an essential cofactor needed for normal functions of various enzymes and its depletion lead to increase DNA damage, genomic instability, deteriorate innate, adaptive immunity, and promote tumor development. It is also linked to tumorigenesis of breast cancer cells through enhancing mammary tumor growth and metastasis. There is insufficient data describing this association in Saudi Arabia. This study aims to determine the prevalence of iron deficiency and its association with breast cancer among premenopausal and postmenopausal women referred for breast cancer screening center in Al Ahsa, Eastern Province of Saudi Arabia. Age, hemoglobin level, iron level, history of anemia, or iron deficiency were collected from patients’ medical records. The included participants were grouped based on their age into premenopausal (<50 years) or postmenopausal (⩾50 years). The definition of low Hb implemented (Hb below 12 g/dL) and low total serum Iron levels (below 8 μmol/L). Logistic regression test was used to compute the association between having a positive cancer screening test (radiological or histocytological) and participant’s lab results. The results are presented as odds ratios and 95% confidence intervals. Thrree hundred fifty-seven women were included, 77% (n = 274) of them were premenopausal. This group cases had more history of iron deficiency (149 [60%] vs 25 (30%), P = .001) compared to those in the postmenopausal group. The risk of having a positive radiological cancer screening test was associated with age (OR = 1.04, 95% CI 1.02-1.06), but negatively was associated with iron level (OR = 0.9, 95% CI 0.86-0.97) among the entire cohort. This study is the first to propose an association between iron deficiency and breast cancer among Saudi young females. This could suggest iron level as a new risk factor that may be used by clinicians to assess breast cancer risk.

Hematopoietic stem/progenitor cell (HSPC) and leukemic cell homing is an important biological phenomenon that occurs through key interactions between adhesion molecules. Tethering and rolling of the cells on endothelium, the crucial initial step of the adhesion cascade, is mediated by interactions between selectins expressed on endothelium to their ligands expressed on HSPCs/leukemic cells in flow. Although multiple factors that affect the rolling behavior of the cells have been identified, molecular mechanisms that enable the essential slow and stable cell rolling remain elusive. Here, using a microfluidics-based single-molecule live cell fluorescence imaging, we reveal that unique spatiotemporal dynamics of selectin ligands on the membrane tethers and slings, which are distinct from that on the cell body, play an essential role in the rolling of the cell. Our results suggest that the spatial confinement of the selectin ligands to the tethers and slings together with the rapid scanning of a large area by the selectin ligands, increases the efficiency of selectin-ligand interactions during cell rolling, resulting in slow and stable rolling of the cell on the selectins. Our findings provide novel insights and contribute significantly to the molecular-level understanding of the initial and essential step of the homing process.

Hematopoietic stem/progenitor cell (HSPC) and leukemic cell homing is an important biological phenomenon that occurs through key interactions between adhesion molecules. Tethering and rolling of the cells on endothelium, the crucial initial step of the adhesion cascade, is mediated by interactions between selectins expressed on endothelium to their ligands expressed on HSPCs/leukemic cells in flow. Although multiple factors that affect the rolling behavior of the cells have been identified, molecular mechanisms that enable the essential slow and stable cell rolling remain elusive. To investigate the molecular mechanisms of cell rolling, an experimental platform that enables molecular level characterization of the adhesion molecules in the context of space, time, and force is required. Here, using a microfluidics-based single-molecule live cell fluorescence imaging, we reveal that unique spatiotemporal dynamics of selectin ligands on the membrane tethers and slings, which are distinct from that on the cell body, play an essential role in the rolling of the cell. Our results suggest that the spatial confinement of the selectin ligands to the tethers and slings together with the rapid scanning of a large area by the selectin ligands, increases the efficiency of selectin-ligand interactions during cell rolling, resulting in slow and stable rolling of the cell on the selectins. Our findings provide novel insights and contribute significantly to the molecular-level understanding of the initial and essential step of the homing process.

Hemoglobin (Hb) disorders or hemoglobinopathies are groups of blood conditions involving inherited genetic diseases – mostly as single-gene autosomal recessive – that lead to the formation of abnormal Hb structure or inadequate to no production of globin chains in Hbs. Disorders of Hb are a global concern since these diseases can cause severe morbidity and early mortality of the affected populations. Treatments vary between chemicals and molecular approaches. The most promising approach is Hb correction. However, the stability of the correction faces a big challenge along with safety concerns. It is worth noting that most of the inherited hemoglobinopathies share common clinical presentations and laboratory findings, although some have distinct features. Hemoglobinopathies with emphasis on recent advances in gene therapy targeting sickle cell disease and thalassemia are discussed in this review.

Super-resolution imaging reveals subtle interplay between nanoscopic organization of membrane ligands and cellular interaction.