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Bleeding disorders and thrombotic complications are major causes of morbidity and mortality with many cases being unexplained. Thrombus formation involves aberrant expression and activation of tissue factor (TF) in vascular endothelial and smooth muscle cells. Here, we sought to identify factors that modulate TF gene expression and activity in these vascular cells. The LIM-only protein FHL2 is a scaffolding protein that modulates signal transduction pathways with crucial functions in endothelial and smooth muscle cells. However, the role of FHL2 in TF regulation and thrombosis remains unexplored. Using a murine model of venous thrombosis in mesenteric vessels, we demonstrated that FHL2 deficiency results in exacerbated thrombus formation. Gain- and loss-of-function experiments revealed that FHL2 represses TF expression in endothelial and smooth muscle cells through inhibition of the transcription factors nuclear factor κB and activating protein-1. Furthermore, we observed that FHL2 interacts with the cytoplasmic tail of TF. In line with our in vivo observations, FHL2 decreases TF activity in endothelial and smooth muscle cells whereas FHL2 knockdown or deficiency results in enhanced TF activity. Finally, the FHL2 single nucleotide polymorphism rs4851770 was associated with the risk of venous thrombosis in a large population of venous thrombosis cases and control subjects from 12 studies (INVENT consortium). Altogether, our results highlight functional involvement of FHL2 in TF-mediated coagulation and identify FHL2 as a novel gene associated with venous thrombosis in humans., (Copyright© 2020 Ferrata Storti Foundation.)

It is unclear whether hyperglycaemia or diabetes mellitus are risk factors for a first venous thrombosis (VT). Self-reported diabetes status and fasting glucose (FG) measures were collected from the Multiple Environmental and Genetic Assessment (MEGA) study to confirm these associations. FG levels were categorized based on the World Health Organization criteria [<6·1 (reference), 6·1-7·0 (2nd), ≥7·0 (3rd) mmol/l]. Logistic regression was performed to quantify the associations. Neither increased FG levels [Odds ratio (95% confidence interval): 0·98 (0·69-1·37) 2nd vs. reference, 0·97 (0·58-1·63) 3rd vs. reference] nor self-reported diabetes [1·12 (0·80-1·58)] were associated with an increased risk of a first VT., (© 2018 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Classical observational studies into the causal relationship between a risk factor and a disease sometimes result in contradictory and spurious findings. This is due to confounding factors. It is not possible to conclude from the results of classical observational studies whether a specific risk factor may be a suitable target for future treatments. A solution is to conduct a Mendelian randomization analysis, which uses genetic variation as a surrogate marker for the risk factor. Mendelian randomisation is based on the idea that characteristics and environmental factors are proportionately divided into carriers and non-carriers of various genetic variants. Mendelian randomisation can be used only if there is a robust relationship between the genetic variant and the risk factor, if the genetic variant is not associated with other factors that confound the relationship between the risk factor and the disease, and if the genetic variant has an effect on the disease only via the risk factor, i.e. not via other biological mechanisms.

The aim of this study was to investigate (potential) research participants' (a) information preferences with regard to receiving biobanks' genetic research results, and (b) attitudes towards the duties of researchers to communicate research results. A total group of 1,678 was analyzed, consisting of a sample of the general Dutch population (N=1,163) and patients with asthma, rhinitis, and thrombosis (N=515) who completed a survey including six fictitious genetic research results each presented as aggregate and individual result, varied for treatability and kind of disease. Five questions assessed attitudes towards researchers' duties to communicate research results. Additionally, background characteristics were measured. A majority of the respondents wanted to receive aggregate results as well as individual results. A small majority (59%) held the view that researchers should communicate individual results with no health consequences. One third agreed with an information duty only when treatment is available. A preference for individual results and an attitude in favor of communicating results were both associated with belonging to the general Dutch population rather than being a patient, wanting to learn about own health as the reason for biobank-participation, a monitoring coping style, a general desire for health information, perceived meaningfulness of genetic information and no anticipated anxiousness. A sizable majority of respondents showed a high information preference for individual results, even when it is unclear that treatment is available. Fewer were of the opinion that researchers should make this possible. For their communication policy biobanks should take notice of (potential) participants' high information preferences and expectations., (Copyright © 2010 Wiley-Liss, Inc.)

Background: Tumor recurrence in the surgical scar after radical hysterectomy for cervical cancer has been reported, but the incidence is unknown. Facts about patient and tumor characteristics and follow-up are lacking. The objective of this study was to analyze the incidence and characteristics of cervical cancer scar recurrences., Methods: All patients who were surgically treated for cervical cancer in our center between 1984 and 2007 were reviewed for scar recurrences. For each case, 5 random controls were selected. Clinical characteristics were compared between the cases and controls., Results: Eleven (1.3%) of 842 patients developed a scar recurrence. Mean time between surgery and scar recurrence was 16 months (range, 2-45 months). For 8 patients (73%), the scar recurrence was the first disease recurrence. Five patients (45%) died, and 2 (18%) were lost to follow-up. Mean time between scar recurrence and death was 9 months. Ninety-one percent of the cases had recurrent disease besides the scar recurrence during follow-up. The case group had a higher percentage of advanced FIGO (International Federation of Gynecology and Obstetrics) stage and postoperatively found involvement of parametria or resection margins and tumor diameter greater than 4 cm, whereas lymph nodes were more often involved in the control group., Conclusions: The incidence of scar recurrences after primary surgery for cervical cancer was 1.3%. Time to development was variable, and prognosis was poor. Besides higher FIGO stage and concurrent unfavorable pathological characteristics, we found no outstanding characteristics of patients with scar recurrence. Scar recurrences go hand in hand with recurrent disease at other locations and seem a manifestation of tumors with extensive metastatic potential.