Machine Learning-Based Prediction of COVID-19 Prognosis Using Clinical and Hematologic Data.

The coronavirus disease 2019 (COVID-19) pandemic is challenging healthcare systems worldwide. The prediction of disease prognosis has a critical role in confronting the burden of COVID-19. We aimed to investigate the feasibility of predicting COVID-19 patient outcomes and disease severity based on clinical and hematological parameters using machine learning techniques. This multicenter retrospective study analyzed records of 485 patients with COVID-19, including demographic information, symptoms, hematological variables, treatment information, and clinical outcomes. Different machine learning approaches, including random forest, multilayer perceptron, and support vector machine, were examined in this study. All models showed a comparable performance, yielding the best area under the curve of 0.96, in predicting the severity of disease and clinical outcome. We also identified the most relevant features in predicting COVID-19 patient outcomes, and we concluded that hematological parameters (neutrophils, lymphocytes, D-dimer, and monocytes) are the most predictive features of severity and patient outcome.

Identification of Potential Poly (ADP-Ribose) Polymerase-1 Inhibitors Derived from Rauwolfia serpentina: Possible Implication in Cancer Therapy.

Poly (ADP-ribose) polymerase-1 (PARP-1) has been recognized as a prospective target for the development of novel cancer therapeutics. Several PARP-1 inhibitors are currently being considered for anticancer drug development and clinical investigation. Lately, natural compounds seem to be excellent alternative drug candidates for cancer treatment. Rauwolfia serpentina is a medicinal plant traditionally used in Indian subcontinents to treat various diseases. This study has been designed to identify the bioactive compounds derived from R. serpentina for possible binding and inhibition of PARP-1 using the molecular docking approach. Thirteen compounds were found to interact with the target with a binding affinity greater than the value of -9.0 kcal/mol. After screening the physicochemical properties, only 5 ligands (ajmalicine, yohimbine, isorauhimbine, rauwolscine, and 1,2-dihydrovomilenine) were found to obey all the parameters of Lipinski's rule of five, showed maximum drug-likeness, and possess no significant toxicity. These ligands displayed strong interactions with target PARP-1 via several hydrogen bonds and hydrophobic interactions. Therefore, these identified compounds derived from R. serpentina can be considered for drug development against cancer-targeting PARP-1.

Elucidating Antiangiogenic Potential of Rauwolfia serpentina: VEGFR-2 Targeting-Based Molecular Docking Study.

Angiogenesis plays a critical role in tumorigenesis as it provides the necessary blood supply to the newly grown solid tumor. It helps maintain the tumor microenvironment, promotes tumor development, progression, and metastasis. The vascular epithelial growth factor (VEGF), interacting with the tyrosine kinase receptor VEGFR-2 on endothelial cells, exerts its proangiogenic activity. Hence, targeting the VEGFR-2 signaling is considered a promising strategy to inhibit angiogenesis and thus cancer treatment. This study aims to identify the bioactive compounds derived from the medicinal herb Rauwolfia serpentina that effectively binds with VEGFR-2. The bioactive compounds of R. serpentina were first screened for their physicochemical properties using the DataWarrior program (version 5.5.0). Finally, 17 compounds that obeyed Lipinski's rule of five and showed good drug-likeness were selected for molecular docking studies. Molecular docking results showed that the ligands ajmalicidine, 1, 2-dihydrovomilenine, rauwolscine, yohimbine, ajmaline, and papaverine interact strongly with the target VEGFR-2 receptor. Hydrogen bonds and hydrophobic interactions stabilized the interactions of these compounds with VEGFR-2. These compounds showed favourable drug-like properties and possess no significant toxicity. Therefore, the findings of this study indicate that the compounds derived from R. serpentina can be considered for the development of antiangiogenic drug candidates by targeting VEGFR-2.

Clinical and hematologic presentations of adults with COVID-19 patients in Jeddah: A case control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), is associated with significant morbidity and mortality. The clinical features of COVID-19 were mentioned in previous studies. However, risk factors for COVID-19 are not fully recognized. The aim of this study is to characterize risk factors and clinical features of COVID-19 disease in Jeddah, Saudi Arabia. METHODS: A retrospective, chart-review, case-control study was conducted at King Abdulaziz University, Jeddah, Saudi Arabia. Demographic, clinical, radiological, and laboratory data on patients diagnosed between March 18 and May 18, 2020 were collected and analyzed. RESULTS: We reviewed medical records on 297 suspected cases of COVID-19. Of these, 175 (59%) tested positive for COVID-19 by polymerase chain reaction (PCR) and considered as cases, while 122 (41%) tested negative and considered as control. COVID-19 positive cases were more likely to be males, and non-health care providers. Hypertension (15%), diabetes (10%) and two or more concurrent comorbidities (54.4%) were more prevalent among COVID-19 patients. Patients presented with fever, cough, and loss of taste/smell were more likely to test positive for COVID-19 (P = 0.001, 0.008, 0.008; respectively). Radiological evidence of pneumonia was associated with confirmed COVID-19 disease (P = 0.001). Shortness of breath and gastrointestinal symptoms were not associated with the risk of COVID-19 at presentation. On admission, white blood cells, neutrophils, lymphocytes, eosinophils, basophils, and platelets were significantly lower among COVID-19 patients compared with controls. Surprisingly, D-Dimer levels were lower among COVID-19 positive patients when compared with controls. CONCLUSION: Male gender, hypertension, and diabetes are the most commonly observed risk factors associated with COVID-19 disease in Jeddah, Saudi Arabia. COVID-19 patient had significantly lower lymphocyte and neutrophil counts.

Response to Hydroxyurea in a Patient With Sickle Cell Hepatopathy: A Case Report.

Sickle cell hepatopathy is an underreported entity lacking clear management guidelines. This case highlights the potential role of hydroxyurea (HU) in improving the hepatic dysfunction seen among patients with sickle cell disease (SCD). We herein present the clinical course of a patient prior to and after the initiation of hydroxyurea with an emphasis on long-term outcomes and the patterns of liver injury over a 15-year time course.

An explanatory mixed methods study on the validity and validation of students' assessment results in the undergraduate surgery course.

BACKGROUND/PURPOSE: There is inadequate evidence of reported validity of the results of assessment instruments used to assess clinical competence. This study aimed at combining multiple lines of quantitative and qualitative evidence to support interpretation and use of assessment results. METHOD: This study is a mixed methods explanatory research set in two stages of data collection and analysis (QUAN : qual). Guided by Messick's conceptual model, quantitative evidences as reliability and correlation coefficients of various validity components were calculated using students' scores, grades and success rates of the whole population of students in 2012/2013 and 2013/2014 (n= 383; 326). The underlying values that scaffold validity evidences were identified via Focus Group Discussions (FGD) with faculty and students; sampling technique was purposive; and results were analyzed by content analysis. RESULTS: (1) Themes that resulted from content analysis aligned with quantitative evidences. (2) Assessment results showed: (a) content validity (table of specifications and blueprinting in another study); (b) consequential validity (positive unintended consequences resulted from new assessment approach); (c) relationships to other variables [a statistically significant correlation among various assessment methods; with combined score (0.64-0.86) and between mid and final exam results (r = 0.672)]; (d) internal consistency (high reliability of MCQ and OSCE: 0.81, 0.80); (3) success rates and grades distribution alone could not provide evidence to advocate an argument on validity of results. CONCLUSION: The unified approach pursued in this study created a strong evidential basis for meaningful interpretation of assessment scores that could be applied in clinical assessments.

Restless legs syndrome and sleep quality among adult sickle cell disease patients.

OBJECTIVE: The purpose of this study is to determine and compare the prevalence of restless legs syndrome (RLS) between adult patients with sickle cell disease (SCD) and non-SCD anemia. METHODS: This cross-sectional study was conducted from December 2013 to July 2014. Patients with SCD and non-SCD anemia were recruited from a hematology clinic at a large university hospital. Patients with secondary RLS were excluded. Data were collected on demographic features, clinical evaluations, laboratory tests, sleep quality using the Pittsburgh Sleep Quality Index, RLS symptoms using the International Restless Legs Syndrome Study Group Criteria, severity of RLS using the International Restless Leg Syndrome Rating Scale, and daytime sleepiness using the Epworth Sleepiness Scale. RESULTS: The study sample consisted of 44 patients with SCD and 45 with non-SCD anemia. The two groups were comparable in age, gender, body mass index, smoking habit, and comorbidities. Poor sleep quality was found in 63% of the SCD group compared to 53% of the non-SCD group. The prevalence of RLS among SCD group and non-SCD group was 13.6% (6/44) and 8.8% (4/45), respectively. These differences, however, were not statistically significant, p > 0.05. Excessive daytime sleepiness was also similar in both groups, with the rate being 20.5 and 17.8% in the SCD and non-SCD groups, respectively. CONCLUSION: Our study revealed that poor sleep quality and RLS were both common among adult patients with SCD; however, they did not differ significantly from patients with non-SCD anemia.

Derivation and differentiation of bone marrow mesenchymal stem cells from osteoarthritis patients.

Osteoarthritis (OA) of the knee is a degenerative joint disease caused by the progressive reduction of the articular cartilage surface that leads to reduced joint function. Cartilage degeneration occurs through gradual loss in extracellular matrix components including type II collagen and proteoglycan. Due to limited inherent self repair capacity of the cartilage, the use of cell-based therapies for articular cartilage regeneration is considered promising. Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent cells and are highly capable of multilineage differentiation which render them valuable for regenerative medicine. In this study, BM-MSCs were isolated from OA patients and were characterized for MSC specific CD surface marker antigens using flowcytometry and their differentiation potential into adipocytes, osteocytes and chondrocytes were evaluated using histological and gene expression studies. BM-MSCs isolated from OA patients showed short spindle shaped morphology in culture and expressed positive MSC related CD markers. They also demonstrated positive staining with oil red O, alizarin red and alcian blue following differentiation into adipocytes, osteocytes and chondrocytes, respectively. In addition, chodrogenic related genes such as collagen type II alpha1, cartilage oligomeric matrix protein, fibromodulin, and SOX9 as well as osteocytic related genes such as alkaline phosphatase, core-binding factor alpha 1, osteopontin and RUNX2 runt-related transcription factor 2 were upregulated following chondrogenic and osteogenic differentiation respectively. We have successfully isolated and characterized BM-MSCs from OA patients. Although BM-MSCs has been widely studied and their potential in regenerative medicine is reported, the present study is the first report in our series of experiments on the BMSCs isolated from OA patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

Incidence and potential causative factors associated with chronic benign neutropenia in the Kingdom of Saudi Arabia.

BACKGROUND: Benign neutropenia often presents in certain populations without any genotype nor phenotype. Middle East countries are among the regions where endemic cases of chronic benign neutropenia are reported in the general population with an incidence of approximately between 10-15%. Not many studies have been performed to ascertain the cause or burden associated with this condition. The objective of the current study was to identify the frequency and characterize the consequences of chronic benign neutropenia in the country of Saudi Arabia. RESULTS: Benign neutropenia was found to be high in the Saudi Arabia general population (up to 20%), with an average neutrophil count of 1.48 (range 0.99 - 1.95 × 10(9)cells/L), with Saudis having a higher incidence of chronic benign neutropenia compared to non-Saudis (p = <0.05). Complete blood count analyses showed significant difference in the total white cell count of neutrophils (p < 0.0001), WBC (p < 0.0001), lymphocytes (p < 0.001), monocytes (p < 0.001), eosinophils (p = 0.013) as well as the CD19 B cells (p = 0.008). CONCLUSIONS: Our study is the first to carefully quantitate benign neutropenia in Saudi Arabia. We identified that this condition is prevalent in the middle aged population (18 years to 55 years). These individuals not only had lower neutrophil counts, but also reduced peripheral blood cells types, especially the B-lymphocyte population (CD19 subset). As B-lymphocytes are involved in antibody production and antigen recognition, a decrease might easily predispose the individuals to infectious agents. As such more mechanistic studies need to be undertaken to understand the cause and potential long-term consequences of benign neutropenia.

Risk factors of coronary heart disease among medical students in King Abdulaziz University, Jeddah, Saudi Arabia.

BACKGROUND: Nowadays, Cardiovascular Diseases (CVDs) represents an escalating worldwide public health problem. Providing consistent data on the magnitude and risk factors of CVDs among young population will help in controlling the risks and avoiding their consequences. OBJECTIVE: The objective was to estimate the prevalence of risk factors of Coronary Heart Disease (CHD) among medical students during their clinical clerkship (4th - 6th years). METHODS: A cross-sectional study was done during the educational year 2012-2013 at King Abdulaziz University (KAU), Jeddah. Ethical standards were followed and a multistage stratified random sample method was used for selection of 214 medical students. Data was collected through an interviewing questionnaire, measurements and laboratory investigations. Both descriptive and analytical statistics were done by SPSS version 21. CHD risk percent in thirty years was calculated using Framingham algorithm for each student, then the risk among all students was determined. RESULTS: The commonest risk factors of CHDs were daily intake of high fat diet (73.4%), physical inactivity (57.9%), overweight/or obesity (31.2%) and daily consumption of fast food (13.1%). Hyper-cholesterolemia (17.2%) and hypertension (9.3%) were also prevalent risk factors. Smoking prevalence was low (2.8%). Males had significantly higher mean scores for most of CHD risk factors compared to females (p < 0.05). Systolic Blood pressure was higher among males (119.47 ± 11.17) compared to females (112.26 ± 9.06). A highly statistical significant difference was present (Students't test = 4.74, p < 0.001). Framingham Risk Score revealed that CHD risk percent in thirty-years among all students was 10.7%, 2.3% and 0.5% for mild, moderate and severe risk, respectively. CONCLUSION: An alarmingly high prevalence of CHD risk factors was prevailed among medical students, especially among males. However, a low prevalence of smoking may indicate the success of "Smoke-free Campus" program. Screening risk factors of CHD among medical students and implementation of intervention programs are recommended. Programs to raise awareness about CHD risk factors, encourage young adult students to adopt a healthy dietary behavior and promote physical exercise should be initiated.

Five novel glucose-6-phosphate dehydrogenase deficiency haplotypes correlating with disease severity.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. An association between enzyme levels and gene haplotypes remains to be established. METHODS: In this study, we determined G6PD enzyme levels and sequenced the coding region, including the intron-exon boundaries, in a group of individuals (163 males and 86 females) who were referred to the clinic with suspected G6PD deficiency. The sequence data were analysed by physical linkage analysis and PHASE haplotype reconstruction. RESULTS: All previously reported G6PD missense changes, including the AURES, MEDITERRANEAN, A-, SIBARI, VIANGCHAN and ANANT, were identified in our cohort. The AURES mutation (p.Ile48Thr) was the most common variant in the cohort (30% in males patients) followed by the Mediterranean variant (p.Ser188Phe) detectable in 17.79% in male patients. Variant forms of the A- mutation (p.Val68Met, p.Asn126Asp or a combination of both) were detectable in 15.33% of the male patients. However, unique to this study, several of such mutations co-existed in the same patient as shown by physical linkage in males or PHASE haplotype reconstruction in females. Based on 6 non-synonymous variants of G6PD, 13 different haplotypes (13 in males, 8 in females) were identified. Five of these were previously unreported (Jeddah A, B, C, D and E) and were defined by previously unreported combinations of extant mutations where patients harbouring these haplotypes exhibited severe G6PD deficiency. CONCLUSIONS: Our findings will help design a focused population screening approach and provide better management for G6PD deficiency patients.

Autoimmune thrombocytopenia. Is it a different disease or different aspects of a single disease?

OBJECTIVE: To evaluate the association between autoimmune thrombocytopenia with other autoimmune disorders, to show if they are different autoimmune diseases or one disease with different presentations at the same time, and to study the effect of treatment on platelet count in different thyroid condition. METHODS: In this retrospective study, we included 141 patients with thrombocytopenic purpura. The result of thyroid function test, thyroid autoantibodies, Coombs' reactivity, anti-nuclear antibody, and double-stranded DNA were analyzed. This study was conducted in the Clinical Hematology Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia between June 2003 and August 2010. RESULTS: There were 51 (36.2%) patients with laboratory evidence of autoimmune disease, 13 (9.2%) with hypothyroidism, and 6 (4.3%) with hyperthyroidism. In addition, 5 (3.5%) patients showed laboratory evidence of Evan syndrome and 3 (2.1%) patients had isolated positive thyroid antibodies. There was non-significant difference (p=0.61) in platelets count after one month of treatment of patients with different thyroid condition. CONCLUSION: Immune thrombocytopenia is associated with evidence of different autoimmune disease or a combination of them, which may appear at presentation or during the course of disease giving evidence that they are different manifestations of a single disease. Screening patients for antithyroid antibodies would identify a patient at risk of developing overt thyroid disease. These patients may be further screened with a thyroid-stimulating hormone assay to detect subclinical thyroid disease.

Detection of FLT3 oncogene mutations in acute myeloid leukemia using conformation sensitive gel electrophoresis.

FLT3 (fms-related tyrosine kinase 3) is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. FLT3 is also expressed on leukemia blasts in most cases of acute myeloid leukemia (AML). In order to determine the frequency of FLT3 oncogene mutations, we analyzed genomic DNA of adult de novo acute myeloid leukemia (AML). Polymerase chain reaction (PCR) and conformation-sensitive gel electrophoresis (CSGE) were used for FLT3 exons 11, 14, and 15, followed by direct DNA sequencing. Two different types of functionally important FLT 3 mutations have been identified. Those mutations were unique to patients with inv(16), t(15:17) or t(8;21) and comprised fifteen cases with internal tandem duplication (ITD) mutation in the juxtamembrane domain and eleven cases with point mutation (exon 20, Asp835Tyr). The high frequency of the flt3 proto-oncogene mutations in acute myeloid leukemia AML suggests a key role for the receptor function. The association of FLT3 mutations with chromosomal abnormalities invites speculation as to the link between these two changes in the pathogenesis of acute myeloid leukemiaAML. Furthermore, CSGE method has shown to be a rapid and sensitive screening method for detection of nucleotide alteration in FLT3 gene. Finally, this study reports, for the first time in Saudi Arabia, mutations in the human FLT3 gene in acute myeloid leukemia AML patients.

Gastrointestinal Non-Hodgkin's lymphoma: a clinico-pathological study.

OBJECTIVES: The aim of this study is to determine the clinico-pathological features of primary gastrointestinal non-Hodgkin's lymphoma (GI NHL) at King Abdulaziz University Hospital, Jeddah, and to compare our results to those reported in the literature. MATERIALS AND METHODS: Twenty-three adult patients with primary GI NHL diagnosed over a 5-year period (2000 through 2005) were retrospectively studied clinically and histopathologically. They were classified using the REAL/WHO histopathologic classification. RESULTS: Of the 23 patients with primary GI NHL, 14 (60.9%) were Saudis, with a male-to-female ratio of 1.3:1. The mean age of male patients was 61. 3 years, ranging from 42-83 years with an SD of +/-13.09; while for females, the mean age was 64 years, ranging from 50-75 years with an SD of +/-9.14. Abdominal pain was the most common presenting symptom (78.3%), and the most common primary site was the stomach (73.9%), followed by the small bowel (13%). The most frequent histologic subtype was the diffuse large B cell lymphoma, accounting for 60.9% of all cases, followed by the marginal-zone cell lymphoma (MALT type), which was Helicobacter pylori associated (39.1%). A large proportion of patients with primary GI NHL had early disease (Stage IE - 20%, Stage IIE - 58.6%). With regards to treatment, 15 patients (65.2%) had chemotherapy, while only 2 patients (8.7%) were treated by Helicobacter pylori eradication. The overall 5-year survival was 47.8%. CONCLUSION: The data demonstrated that primary GI NHL is more common among males, mainly in their sixth decade. Abdominal pain is the most common presenting symptom, with stomach being the most common involved site. Diffuse large B cell lymphoma is the most frequent histologic subtype, followed by extranodal marginal-zone B cell lymphoma (MALT type), which was Helicobacter-associated. A majority of cases have early disease (stage IE and IIE), mostly treated by combination chemotherapy.