Invasion of gastric epithelium represents a hitherto unappreciated trait of H. pylori that could contribute to the bacterium's ability to establish persistent infection that evades the mucosal immune defense and sometimes also antimicrobial therapy. A small number of bacterial cells with a transient intracellular habitat could serve as a seeder population, providing a backup for a constantly challenged and fluctuating luminal population.
This study highlights several aspects of H. pylori aging in vitro and shows some of the differences that exist between bacillary and coccoid forms. This information is important for understanding the transmission and survival of H. pylori outside the human host, as the degradative changes in the intracellular composition and the surface properties shown here point to dead bacteria, and not to a viable but nonculturable form.
Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of < 3.0. A lower time in therapeutic range was associated with a higher risk of CRB. Conclusions CRB is a frequent complication in cancer patients with VTE during anticoagulant treatment, and is associated with age > 75 years and intracranial malignancy.
Purpose
It is not known if mammographic breast compression of a primary tumor causes shedding of tumor cells into the circulatory system. Little is known about how the detection of circulating biomarkers such as circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) is affected by breast compression intervention.
Methods
CTCs and ctDNA were analyzed in blood samples collected before and after breast compression in 31 patients with primary breast cancer scheduled for neoadjuvant therapy. All patients had a central venous access to allow administration of intravenous neoadjuvant chemotherapy, which enabled blood collection from superior vena cava, draining the breasts, in addition to sampling from a peripheral vein.
Results
CTC and ctDNA positivity was seen in 26% and 65% of the patients, respectively. There was a significant increase of ctDNA after breast compression in central blood (
p
= 0.01), not observed in peripheral testing. No increase related with breast compression was observed for CTC. ctDNA positivity was associated with older age (
p
= 0.05), and ctDNA increase after breast compression was associated with high Ki67 proliferating tumors (
p
= 0.04). CTCs were more abundant in central compared to peripheral blood samples (
p
= 0.04).
Conclusions
There was no significant release of CTCs after mammographic breast compression but more CTCs were present in central compared to peripheral blood. No significant difference between central and peripheral levels of ctDNA was observed. The small average increase in ctDNA after breast compression is unlikely to be clinically relevant. The results give support for mammography as a safe procedure from the point of view of CTC and ctDNA shedding to the blood circulation. The results may have implications for the standardization of sampling procedures for circulating tumor markers.
Electronic supplementary material
The online version of this article (10.1007/s10549-019-05326-5) contains supplementary material, which is available to authorized users.
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