Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase ...isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT.
This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes.
A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively).
GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.
Cardiac complications occur in patients with non-transfusion dependent thalassemia (NTDT). The study aimed to evaluate transfusion effect on systolic and diastolic cardiac function in young NTDT ...patients. Methods: Study design: Cohort study. Seventeen regularly-transfused patients with NTDT (12.5±5.3 years; group 1) and 15 none/minimally transfused patients (13.2±4.8 years; group 2) were followed up for 5 years and compared as regards their clinical parameters, echocardiographic and Tissue-Doppler-Imaging.
Group 2 patients had significantly higher peak late-diastolic velocity of the left-ventricular-inflow Doppler (Am). Mitral-valve A-wave duration/pulmonary-veins, A-wave duration-ratio and pulmonary-vein S/D velocities-ratio were larger in group 2 as well (p = < 0.01). The diameters of right and left outflow-tract were larger with a higher cardiac-index in patients of group 2. Systolic-function was similar in the 2 studied groups.
Diastolic function assessment revealed indicators of an abnormal relaxation of left-ventricle in non-transfused patients, which suggests a diastolic dysfunction. An increase in the diameter of the outflow-tract is likely attributed to high cardiac-output status in non-transfused NTDT patients as they have a higher cardiac index. Early start of regular transfusion for NTDT patients might prevent serious long-term cardiac complications.
α-Thalassemia (α-thal) is the most common autosomal recessive hemoglobinopathy. There is a vast diversity and geographical variability in underlying genotypes in Hb H (β4) patients. Herein, we ...describe the genotypes found in the largest report of Omani Hb H patients. Moreover, we reviewed and summarized the literature published from the Eastern Mediterranean region. A retrospective review of all genetically confirmed Hb H disease patients diagnosed between 2007 and 2017 at Sultan Qaboos University Hospital, Muscat, Oman, was performed. Hematological parameters and clinical presentations were assessed. Both α-globin genes were screened for deletional and nondeletional mutations using a stepwise diagnostic strategy as described before. A total of 52 patients (27 females and 25 males) with a mean age of 20.6 years (range 0.23-80.0) were molecularly confirmed to carry Hb H disease. The patients had a hemoglobin (Hb) level of 9.3 g/dL (range 5.7-13.0) and mean corpuscular volume (MCV) of 58.4 fL (range 48.2-82.1). A total of eight genotype combinations were identified, with α2 polyadenylation signal mutation (polyA1) (AATAAA>AATAAG (α
PA1
α/α
PA1
α), often cited as α
T-Saudi
α/α
T-Saudi
α, being the most common (53.8%) followed by -α
3.7
/- -
MED I
(28.8%). Our cohort also included patients with combinations of α
PA1
with other Hb variants: α
PA1
α/α
PA1
α with Hb S (HBB: c.20A>T) trait (n = 2), -α
3.7
/α
PA1
α (n = 2) and α
codon 19
α (HBA2: c.56delG)/α
PA1
α (n = 1). Nondeletional Hb H disease due to the α
PA1
mutation is the most common in Omanis. Molecular diagnosis is necessary for accurate confirmation of the diagnosis of α-thal, determination of underlying genotypes, follow-up and counseling.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Previous studies have reported that cancer incidence trends in Oman varied by tumor site and sex. No comprehensive analysis of all cancer sites had been reported. The objective of this study is to ...analyze cancer incidence trends in Oman and calculate the annual percent change (APC) in age-standardized rates (ASRs) for all-cancer and 61 individual cancer sites in Omani men and women from 1996 to 2019.
We gathered incidence data from The Omani National Cancer Registry for all cancers combined and individual tumor sites. We estimated the APC using Poisson regression.
The cancer ASR in the Omani population increased by 23% (from 95/100,000 in 1996 to 117.2/100,000 in 2019), with the increase being more pronounced in females (48%
7% in males). Among the male population, there was significant increase in the ASRs of colon, rectum, thyroid, and prostate cancers, with APCs of 6.92%, 4.24%, 4.19%, and 2.03%, respectively. Among females, all-cancer incidence showed significant increase (APC = 1.39%), and increasing trends were observed in uterine, colon, rectum, thyroid, and breast cancers (APCs = 7.57%, 7.08%, 5.19%, 5.16%, and 4.19%, respectively).
The ASR of all-cancer increased significantly in Omani women but not in men. Uterine cancer had the highest APC. Colorectal cancer and thyroid ASR increased in both males and females. Breast and prostate cancers showed increasing trends. Further research is needed to explore factors contributing to increasing cancer incidences.
Urogenital cancers, which include prostate, bladder, and kidney malignancies, exert a substantial impact on global cancer-related morbidity and mortality. Proteomic biomarkers, emerging as valuable ...tools, aim to enhance early detection, prognostic accuracy, and the development of personalized therapeutic strategies. This study undertook a comprehensive systematic review and meta-analysis of the existing literature investigating the role and potential of proteomic biomarkers in plasma, tissue, and urine samples in urogenital cancers. Our extensive search across several databases identified 1879 differentially expressed proteins from 37 studies, signifying their potential as unique biomarkers for these cancers. A meta-analysis of the significantly differentially expressed proteins was executed, accentuating the findings through visually intuitive volcano plots. A functional enrichment analysis unveiled their significant involvement in diverse biological processes, including signal transduction, immune response, cell communication, and cell growth. A pathway analysis highlighted the participation of key pathways such as the nectin adhesion pathway, TRAIL signaling pathway, and integrin signaling pathways. These findings not only pave the way for future investigations into early detection and targeted therapeutic approaches but also underscore the fundamental role of proteomics in advancing our understanding of the molecular mechanisms underpinning urogenital cancer pathogenesis. Ultimately, these findings hold remarkable potential to significantly enhance patient care and improve clinical outcomes.
Objectives: We sought to define the prevalence of isocitrate dehydrogenase (IDH) mutations, evaluate the clinicopathologic impact of IDH mutations, assess the effect of IDH mutations on the response ...to the currently offered treatment for acute myeloid leukemia (AML) cases, and determine the impact of other common concurrent mutations with IDH.
Methods: A single-center retrospective cohort study was conducted at Sultan Qaboos University Hospital (SQUH) from October 2009 to October 2019. We included all Omani patients (pediatric and adult) treated at SQUH with the standard therapy, for whom DNA extraction was performed at diagnosis. The target mutations in both IDH1 and IDH2 genes were screened using the direct polymerase chain reaction product sequencing method. Statistical analysis was conducted using SPSS software. Survival differences were estimated using the log-rank test. Continuous variables were presented as median (IQRs), while categorical variables were presented as frequency.
Results: A total of 61 patients treated, for whom DNA extraction was performed at diagnosis were evaluated. The median age was 40 (range equivalent 25.5-65.5). The prevalence of IDH1 R132, IDH2 R140, and IDH2 R172 mutations among the study group was 6.6%, 3.3%, and 1.6%, respectively. Clinicopathologic characteristics associated with IDH mutations at diagnosis included older age, lower white blood cell count, higher median platelet counts, normal karyotype AML, and cytogenetics intermediate-risk group. The overall survival (OS) in patients harboring IDH mutations was poor, with a median OS of nine months. This analysis confirms that the response rate and OS for both IDH-mutated and IDH wild-type AML patients were comparable. This will provide contemporary data to be used for comparison with the results of novel investigational (e.g., selective IDH inhibitor) strategies.
Conclusions: The current study results were consistent with the other international studies of IDH mutations in AML and demonstrate the poor prognosis associated with IDH mutations. Clinicopathologic features associated with IDH mutations included older age, lower white blood cell count, higher median platelet counts, normal karyotype AML, and cytogenetics intermediate-risk group.
The objective of our present study was to develop a warfarin dosing algorithm for the Omani patients, as performances of warfarin dosing algorithms vary across populations with impact on the daily ...maintenance dose. We studied the functional polymorphisms of CYP2C9, CYP4F2 and VKORC1 genes to evaluate their impact on the warfarin maintenance dose in an admixed Omani patient cohort with Caucasian, African and Asian ancestries. We observed a 64-fold inter-patient variability for warfarin to achieve stable international normalized ratio in these patients. Univariate analysis revealed that age, gender, weight, atrial fibrillation, deep vein thrombosis/pulmonary embolism and variant genotypes of CYP2C9 and VKORC1 loci were significantly associated with warfarin dose in the studied patient population. However, multiple regression model showed that only the atrial fibrillation, and homozygous CYP2C9 variant genotypes (*2/*3 and *3/*3) and VKORC1 GA and AA genotypes remained significant. A multivariate model, which included demographic, clinical and pharmacogenetic variables together explained 63% of the overall inter-patient variability in warfarin dose requirement in this microgeographically defined, ethnically admixed Omani patient cohort on warfarin. This locally developed model performed much better than the International Warfarin Pharmacogenetics Consortium (IWPC) model as the latter could only explain 34% of the inter-patient variability in Omani patients. VKORC1 3673G>A polymorphism emerged as the single most important predictor of warfarin dose variability, even in this admixed population (partial R(2)=0.45).
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