Objectives To review studies developing or validating a prognostic model for individual venous thromboembolism (VTE) recurrence risk following cessation of therapy for a first unprovoked VTE. Prediction of recurrence risk is crucial to informing patient prognosis and treatment decisions. The review aims to determine whether reliable prognostic models exist and, if not, what further research is needed within the field.

Design Bibliographic databases (including MEDLINE, EMBASE and the Cochrane Library) were searched using index terms relating to the clinical field and prognosis. Screening of titles, abstracts and subsequently full texts was conducted by 2 reviewers independently using predefined criteria. Quality assessment and critical appraisal of included full texts was based on an early version of the PROBAST (Prediction study Risk Of Bias Assessment Tool) for risk of bias and applicability in prognostic model studies.

Setting Studies in any setting were included.

Primary and secondary outcome measures The primary outcome for the review was the predictive accuracy of identified prognostic models in relation to VTE recurrence risk.

Results 3 unique prognostic models were identified including the HERDOO2 score, Vienna prediction model and DASH score. Quality assessment highlighted the Vienna, and DASH models were developed with generally strong methodology, but the HERDOO2 model had many methodological concerns. Further, all models were considered at least at moderate risk of bias, primarily due to the need for further external validation before use in practice.

Conclusions Although the Vienna model shows the most promise (based on strong development methodology, applicability and having some external validation), none of the models can be considered ready for use until further, external and robust validation is performed in new data. Any new models should consider the inclusion of predictors found to be consistently important in existing models (sex, site of index event, D-dimer), and take heed of several methodological issues identified through this review.

PROSPERO registration number CRD42013003494.

https://bmjopen.bmj.com/content/bmjopen/6/5/e011190.full.pdf

Systematic review of prognostic models for recurrent venous thromboembolism (VTE) post-treatment of first unprovoked VTE

Mariya A. Smetanina, Andrey I. Shevela, Konstantin A. Gavrilov, Maxim L. Filipenko Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia. Department of Fundamental Medicine, V. Zelman Institute for Medicine and Psycology (NSU), Novosibirsk 630090, Russia. Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia. Department of Surgical Diseases, V. Zelman Institute for Medicine and Psycology (NSU), Novosibirsk 630090, Russia. Department of Clinical Biochemistry, V. Zelman Institute for Medicine and Psycology (NSU), Novosibirsk 630090, Russia.

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The genetic constituent of varicose vein pathogenesis as a key for future treatment option development

Objective To investigate the association of polymorphisms located near the FOXC2 gene with the risk of varicose veins in ethnic Russians. Methods Allele, genotype, and haplotype frequencies were determined in the sample of 474 patients with primary varicose veins and in the control group of 478 individuals without a history of chronic venous disease. Results Polymorphisms rs7189489, rs4633732, and rs1035550 showed the association with the increased risk of varicose veins, but none of the observed associations remained significant after correction for multiple testing. Haplotype analysis revealed the association of haplotype rs7189489 C–rs4633732 T–rs34221221 C–rs1035550 C–rs34152738 T–rs12711457 G with the increased risk of varicose veins (OR = 2.67, P = 0.01). Conclusions Our results provide evidence that the studied polymorphisms do not play a major role in susceptibility to varicose veins development in the Russian population.

Association of polymorphisms near the FOXC2 gene with the risk of varicose veins in ethnic Russians

Эпигенетика популяций, экотоксикогенетика и болезни человека

Дифференциальная экспрессия генов и активация сигнальных путей в радиорезистентных и радиочувствительных раковых клеточных линиях

Varicose veins of the lower limbs are one of the most common and wide-spread pathology all around the world. What triggers the specific changes in a vein wall still remains unclear as well as what happens in the layers of the vein wall after the disease starts. The aim of the article is to analyze published data and results of researches on epidemiology, genetics, cellular and molecular mechanisms underlying varicose veins pathogenesis. It is now commonly accepted that vein wall changes in patients with varicose veins result from vein-specific inflammation. This process includes leukocytes adhesion to venous endothelium with their subsequent migration into the vein wall and surrounding tissues. Activated leukocytes express a number of molecules that lead to vein wall remodeling and dilation. Comprehensive assessment of the epidemiological data on the prevalence of varicose veins and risk factors, of the findings from genetic studies, of data on molecular-cell interactions as well as results of various surgical interventions in patients with varicose veins, shows that remodeling is a reversible process that can be stopped and reversed by different stimuli including some chemical substances. For the first time in the literature, the authors assume that varicose veins can be successfully cured pharmacologically with no surgical interventions needed.

/pdf/varicose-veins-on-the-verge-of-discovering-the-cause-2e990z23i0.pdf

Varicose veins: on the verge of discovering the cause?

Aim: to study the prevalence of various risk factors (RF) for venous thromboembolic events (VTEE) and their association with D-dimer levels.
Subjects and methods. The clinical, demographic, anthropometric, anamnestic, and laboratory data were analyzed in 106 patients (73 men and 33 women) aged 18 to 78 years admitted to hospital with the first or recurrent episode of VTEE.
Results. RF and VTEE-associated diseases were identified in all patients. Over 90% of the patients had more 2 RFs. The most common RFs were the age above 40 years (85%) and overweight (82%), including obesity (42%). There was a preponderance of cardiovascular diseases in the pattern of VTEE-associated diseases. The direct causes (precipitating factors) of thrombosis were revealed in 57% of cases; the thrombotic episode was classified as idiopathic in 43%. Elevated D-dimer levels were found in 74% of the patients. Higher D-dimer content was seen in women, non-smokers, patients operated on for thrombosis, those who had 2 precipitating factors or more, and those who had a less than 30-day history of thrombosis. There was an inverse correlation between the elevated level of D-dimer and the duration of thrombosis by the moment of its identification (thrombus age). 
Conclusion. All patients who have experienced a venous thrombotic episode have various RFs for VTEE. The content of D-dimer exceeds the normal value in most patients with VTEE. Among the RFs studied, thrombus age is the most important factor associated with elevated D-dimer levels in patients with VTEE.

Кириенко Александр Иванович

Papers

Varicose veins: on the verge of discovering the cause?

Risk factors for venous thromboembolic events and their association with D-dimer level