Rivaroxaban is a safer and more effective alternative to warfarin. However, there are reports of some cases of major hemorrhagic complications associated with rivaroxaban that significantly impair the patients' quality of life and can lead to a fatality. Personalized therapy, including pharmacogenetic testing, may help prevent such adverse events. This study aimed to investigate how ABCB1 3435C>T (rs1045642) and CYP3A5 6986A>G (rs776746) gene polymorphisms, when carried by a patient taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery, affect prothrombin time (PT). Sixty-five patients participated in the study. Their genotypes were identified by PCR in real time. To learn PT peculiar to each patient, we collected venous blood on the 5th day of their anticoagulation therapy, 1 hour before they took rivaroxaban and 3 hours after. Having calculated %ΔPT, we divided the patients into 2 groups: 1) %ΔPT ≤ 0 (n = 7; 10.8%); 2) %ΔPT > 0 (n = 58; 89.2%). Regarding the distribution of rs1045642 polymorphism, we determined the difference between the groups to be statistically significant (χ2 = 6.64; p = 0.027). As for rs776746 polymorphism, the difference was insignificant (χ2 = 0.101; p = 1.0). We discovered that rs1045642 polymorphism has a significant effect on PT variance in patients taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery.
VIEWS 4451
Early detection of dorsopathies is an urgent task for primary care physicians, since such conditions can combine with other chronic noncommunicable diseases (NСD) and adversely affect the course all comorbidities, consequently disimproving the quality of life of patients and increasing the frequency of their requests for medical assistance. This study aimed to determine the value of routine checkups in the context of detection of dorsopathies, NCD, and identification of risk factors (RF). We have retrospectively analyzed the patient records database of a rural outpatient clinic in the Tver region (years 2015 to 2017). The prevalence of dorsopathies and NCD RF were the subjects investigated. Fisher's exact test and Spearman's rank correlation coefficient (SRCC) were applied for the purposes of statistical processing of the results. We discovered that dorsopathy most often was a comorbidity to arterial hypertension and gastrointestinal tract diseases; it was strongly related to the NCD (SRCC = 0.506), age (SRCC = 0.383), slightly less so — to hypodynamia (SRCC = 0.146), type of the patient's occupation (intellectual or physical labor) (SRCC = 0.07). Routine checkups improve the rate of detection of dorsopathy: the more patients undergo such examinations, the more cases of dorsopathy are diagnosed. Thus, it is necessary to increase the number of working people attending the checkups in order to detect dorsopathies early and prevent them effectively.
VIEWS 4362
Contrast-enhanced radiotherapy (CERT) is a binary treatment modality in which the absorbed radiation dose is not only determined by the parameters of the external radiation source but also affected by the concentration of a dose-enhancing agent (DEA) in the studied object. In this work we assessed the distribution of the absorbed dose in a murine B16F10 melanoma injected with a single dose of an aqueous Bi-DTPA solution. The mice were exposed to a single fraction of X-ray irradiation for 28.5 min. In vivo measurements of DEA concentrations were done on a micro-CT scanner using the radiopacity values of malignant tissues from the obtained CT images. We found that the presence of DEA enhanced the absorbed dose more than twofold in 6% of the tumor volume; in 29% of the tumor volume the absorbed dose increased more than onefold. The tumor growth delay time calculated for our model was 0.76 days (we only accounted for the damage caused directly by radiation), whereas in our previous research study tumor growth delay was 10 days. This discrepancy may indicate that in the tumors exposed to contrast-enhanced radiotherapy growth delay results from both the damage directly caused by radiation and other antitumor mechanisms.
VIEWS 4659
The actual prevalence of genetic variants causing familial hypercholesterolemia (FH) in every population remains unknown. The aim of this work was to determine the spectrum of pathogenic variants in patients with acute coronary syndrome (ACS) and clinically diagnosed FH using targeted sequencing. We selected 38 patients with ACS from the sample of 2,081 participants of two multicenter observational studies (2004–2007; 2014–2016) who had a clinical diagnosis of FH based on the Dutch Lipid Clinic Network score and Simon Broome criteria. The men and women included in the study were ≤ 55 and ≤ 60 years of age, respectively. Molecular genetic screening was done by targeted next-generation sequencing. We started by sequencing 3 genes associated with FH, including LDLR, APOB, and PCSK9. If no relevant variants were detected, the panel was expanded. Of 38 patients, 24 (63.2%) were shown to have mutations that could cause clinical manifestations of FH and premature coronary artery disease. All patients were heterozygous carriers. Mutations were detected in three “classic” genes LDLR, APOB, and PCSK9 associated with FH, as well as in other genes involved in lipid metabolism, such as APOE, ABCA1, ABCG5, ABCG8, LPL, ANGPTL3, and MTTP. Five variants detected in our study sample had not been described previously: the pathogenic p.Val273_Cys313del variant of the LDLR gene, the likely pathogenic p.Arg160His variant in the APOE gene, two variants of uncertain significance p.Glu612Lys and c.*415G>A in the PCSK9 gene, and the mutant variant p.Ala776Ser in the LDLR gene. We conclude that the use of clinical diagnostic criteria in patients with ACS and FH enables identification of carriers of both “classic” mutations associated with FH and rare genetic variants that can be phenotypically expressed as FH.
VIEWS 4267