Impact of Genetic Variations on Thromboembolic Risk in Saudis with Sickle Cell Disease.

BACKGROUND: Sickle cell disease (SCD) is a Mendelian disease characterized by multigenic phenotypes. Previous reports indicated a higher rate of thromboembolic events (TEEs) in SCD patients. A number of candidate polymorphisms in certain genes (e.g., FVL, PRT, and MTHFR) were previously reported as risk factors for TEEs in different clinical conditions. This study aimed to genotype these genes and other loci predicted to underlie TEEs in SCD patients. METHODOLOGY: A multi-center genome-wide association study (GWAS) involving Saudi SCD adult patients with a history of TEEs (n = 65) and control patients without TEE history (n = 285) was performed. Genotyping used the 10× Affymetrix Axiom array, which includes 683,030 markers. Fisher's exact test was used to generate p-values of TEE associations with each single-nucleotide polymorphism (SNP). The haplotype analysis software tool version 1.05, designed by the University of Göttingen, Germany, was used to identify the common inherited haplotypes. RESULTS: No association was identified between the targeted single-nucleotide polymorphism rs1801133 in MTHFR and TEEs in SCD (p = 0.79). The allele frequency of rs6025 in FVL and rs1799963 in PRT in our cohort was extremely low (<0.01); thus, both variants were excluded from the analysis as no meaningful comparison was possible. In contrast, the GWAS analysis showed novel genome-wide associations (p < 5 × 10-8) with seven signals; five of them were located on Chr 11 (rs35390334, rs331532, rs317777, rs147062602, and rs372091), one SNP on Chr 20 (rs139341092), and another on Chr 9 (rs76076035). The other 34 SNPs located on known genes were also detected at a signal threshold of p < 5 × 10-6. Seven of the identified variants are located in olfactory receptor family 51 genes (OR51B5, OR51V1, OR51A1P, and OR51E2), and five variants were related to family 52 genes (OR52A5, OR52K1, OR52K2, and OR52T1P). The previously reported association between rs5006884-A in OR51B5 and fetal hemoglobin (HbF) levels was confirmed in our study, which showed significantly lower levels of HbF (p = 0.002) and less allele frequency (p = 0.003) in the TEE cases than in the controls. The assessment of the haplotype inheritance pattern involved the top ten significant markers with no LD (rs353988334, rs317777, rs14788626882, rs49188823, rs139349992, rs76076035, rs73395847, rs1368823, rs8888834548, and rs1455957). A haplotype analysis revealed significant associations between two haplotypes (a risk, TT-AA-del-AA-ins-CT-TT-CC-CC-AA, and a reverse protective, CC-GG-ins-GG-del-TT-CC-TT-GG-GG) and TEEs in SCD (p = 0.024, OR = 6.16, CI = 1.34-28.24, and p = 0.019, OR = 0.33, CI = 0.13-0.85, respectively). CONCLUSIONS: Seven markers showed novel genome-wide associations; two of them were exonic variants (rs317777 in OLFM5P and rs147062602 in OR51B5), and less significant associations (p < 5 × 10-6) were identified for 34 other variants in known genes with TEEs in SCD. Moreover, two 10-SNP common haplotypes were determined with contradictory effects. Further replication of these findings is needed.

The effect of intermittent fasting on the clinical and hematological parameters of patients with sickle cell disease: A preliminary study.

Introduction: Sickle cell disease is a genetic disorder that frequently presents with vaso-occlusive crisis (VOC). Most patients with sickle cell disease in Qatar are Muslims; hence, they practice intermittent fasting during the holy month of Ramadan. However, there is a paucity of literature describing the effect of intermittent fasting on the occurrence of severe VOC. As a result, there is a lack of guidelines or standardized protocols that can help physicians advise patients with sickle cell disease who wish to practice intermittent fasting. Therefore, this study's aim was to investigate the effect of intermittent fasting on the clinical and hematological parameters of individuals with sickle cell disease. Methods: We conducted a retrospective study for 52 Muslim patients with sickle cell disease in Qatar aged ≥18 years who were confirmed to be fasting during the holy month of Ramadan during any of the years 2019-2021. The difference in the occurrence of severe VOC, hemolytic crisis, and other clinical, hematological, and metabolic parameters were studied one month before, during, and one month after the intermittent fasting of Ramadan using the patient's medical records. Mean (sd), median (IQR), and frequency (%) described the data. One-way with repeated measures ANOVA with a Greenhouse-Geisser correction and Friedman tests (*) were used at alpha level 0.05. Results: The study participants' (mean±sd) age was (31.1±9.2) years, 51.9% were males, and 48.1% were females. Roughly seventy percent of the participants were of Arab ethnicity, while the rest were either African or Asian. Most of the patients were homozygotes (SS) (90.4%). The median number of severe VOC (P = 0.7) and hemolytic crisis (P = 0.5) was not found to be significantly different before, during, or after Ramadan. Significant differences, however, were found in platelet count (P = 0.003), reticulocyte count (P < 0.001), and creatinine level (P = 0.038) with intermittent fasting. Discussion: In this preliminary study, intermittent fasting does not seem to influence the rate of occurrence of severe vaso-occlusive crisis or hemolytic crisis in patients with sickle cell disease; however, it was found to be associated with differences in platelet count, reticulocytes count, and creatinine level. The statistical and clinical significance of these findings needs to be confirmed in studies with a larger sample size.

Outcome of children older than one year with neuroblastoma.

OBJECTIVE: To assess the outcome of children older than one year with neuroblastoma treated at King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia. METHODS: We retrospectively reviewed the files of 52 children older than one year with neuroblastoma (NBL) treated at our center between September 1987 and May 2003. Treatment consisted of OPEC chemotherapy regimen (vincristine, cisplatin, etoposide, and cyclophosphamide) or alternating OPEC/OJEC (carboplatin in place of cisplatin), surgical resection +/- radiotherapy (RT). No patient received high dose therapy (HDT). RESULTS: Thirty-four patients (65%) were stage 4, 12 (23%) stage 3, and 6 (11%) stage 2. Three stage 2 patients were treated with surgery only, all are alive in complete remission (CR). All stage 3 and 4 patients were treated with chemotherapy and surgery +/- RT. After induction chemotherapy, CR was achieved in 17 patients (32%) and partial remission in 10 (19%). Complete surgical resection was possible in 11 patients (22%). Disease recurrence or progression occurred in 27 patients (51%). With a median follow-up of 24 months (range 4-120), the 2-year event free survival was 10%, 82%, and 87% and the overall survival was 12%, 83%, and 100% for stage 4, 3, and 2. CONCLUSION: Children older than one year with localized NBL have good prognosis compared to those with stage 4. The use of HDT may improve the outcome in the latter group. Toxicity was significant, and adoption of risk-stratified treatment may help to reduce treatment complications.

Physical assault on a medical resident.

We report a physical assault on a 25-year-old male medical resident who was on-call in the emergency room. Causes of assault on physicians as well as how they can be avoided are discussed.