No abstract

To assess the role of noninvasive tests--quantitative photoplethysmography, air plethysmography, and quantitative duplex scanning, we compared a group of normal (group N, eight limbs) volunteers to patients with severe chronic venous insufficiency who were stratified according to the degree of reflux seen on the current "gold standard," descending phlebography. Group M (10 limbs) had mild (grades 0 to 2) reflux, and group S (10 limbs) had severe (grades 3 to 4) reflux as determined by phlebography. Quantitative photoplethysmography could identify normal from abnormal limbs but could not distinguish the severity of reflux. Air plethysmography was used to calculate venous filling index, ejection fraction, and residual volume fraction. Ejection fraction was the same in all groups. Venous filling index could not significantly distinguish the degree of reflux (group M vs group S) but increased as reflux increased. Residual volume fraction was considerably higher in group S. Quantitative duplex valve closure time was measured in the superficial femoral and popliteal veins, with the values added together in each limb to give a total valve closure time (TVCT). A TVCT value greater than or equal to 4 seconds correlated best with severe phlebographic reflux, with a sensitivity of 90%, a specificity of 94%, and an accuracy of 93%. This value was confirmed as the best test for venous reflux by receiver operating characteristic curve analysis. Thus in the evaluation of patients with severe chronic venous insufficiency who are candidates for phlebography and surgery, quantitative duplex measurement of TVCT gives the best noninvasive assessment of the severity of deep venous reflux.

BackgroundGene panel testing has become the norm for assessing breast cancer (BC) susceptibility, but actual cancer risks conferred by genes included in panels are not established. Contrarily, deciphering the missing hereditability on BC, through identification of novel candidates, remains a challenge. We aimed to investigate the mutation prevalence and spectra in a highly selected cohort of Greek patients with BC, questioning an extensive number of genes, implicated in cancer predisposition and DNA repair, while calculating gene-specific BC risks that can ultimately lead to important associations.MethodsTo further discern BC susceptibility, a comprehensive 94-cancer gene panel was implemented in a cohort of 1382 Greek patients with BC, highly selected for strong family history and/or very young age (<35 years) at diagnosis, followed by BC risk calculation, based on a case–control analysis.ResultsHerein, 31.5% of patients tested carried pathogenic variants (PVs) in 28 known, suspected or candidate BC predisposition genes. In total, 24.8% of the patients carried BRCA1/2 loss-of-function variants. An additional 6.7% carried PVs in additional genes, the vast majority of which can be offered meaningful clinical changes. Significant association to BC predisposition was observed for ATM, PALB2, TP53, RAD51C and CHEK2 PVs. Primarily, compared with controls, RAD51C PVs and CHEK2 damaging missense variants were associated with high (ORs 6.19 (Exome Aggregation Consortium (ExAC)) and 12.6 (Fabulous Ladies Over Seventy (FLOSSIES)), p<0.01) and moderate BC risk (ORs 3.79 (ExAC) and 5.9 (FLOSSIES), p<0.01), respectively.ConclusionStudying a large and unique cohort of highly selected patients with BC, deriving from a population with founder effects, provides important insight on distinct associations, pivotal for patient management.