Physical Activity Improves Borderline Ankle-Brachial Index Values in a Cardiovascular Risk Population

Background: Peripheral, arterial disease (PAD) is an underdiagnosed and undertreated disease because it remains asymptomatic for so long. The ankle brachial index (ABI) is a valid method for detecting PAD: in lower extremities. ABI Methods: A total of 193 subjects with borderline ABI were examined in 2005-2006. None of them had previously diagnosed diabetes, cardiovascular or renal disease or intermittent claudication. They were given conventional treatment for multiple risk factors of cardiovascular diseases (hypertension, hypercholesterolemia, elevated blood glucose, smoking, and overweight). Sixty-four percent of these subjects (n = 1.23) attended a follow-up visit in 2012. Results: Of the 123 subjects with borderline ABI (mean age 59.0 years, 62% female) at baseline, 18 (15%, 95% confidence intervals {Cl] 9%-22%) developed incident PAD during the follow-up. The mean ABI was 0.97 +/- 0.03 at baseline and 1.01 +/- 0.12 at 7-year follow-up visit. The change in mean ABI was 70:04 (95% CI: 0.03-0.07), P <0.001. ABI improved significantly in 25 (20%) subjects. In multivariate ordered logistic regression analyses high and even moderate leisure-time physical activity :(LTPA; odds ratio 6.15; 95% CI: 1.99-19.1) predicted a rise in ABI in comparison to low LTPA. Conclusions: Physical activity seems to improve significantly ABI values among men and women with borderline ABI (0.91-1.00).Peer reviewe

Expression of markers of stem cell characteristics, epithelial-mesenchymal transition, basal-like phenotype, proliferation, and androgen receptor in metaplastic breast cancer and their prognostic impact

Background Metaplastic breast cancer (MpBC) is a heterogeneous subtype of invasive mammary carcinoma associated with epithelial-mesenchymal transition (EMT) and cancer stem cell characteristics. Data regarding prognostic markers and potentially actionable targets for therapy are still limited. The present study aimed to characterize the immunohistochemical landscape of this rare malignancy and to identify potential prognostic factors and targets for therapy. Material and methods A total of 75 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for Ki-67 (MIB-1), epidermal growth factor receptor (EGFR), cytokeratin 5/6, vimentin, CD44, and androgen receptor (AR) and correlated their expression with clinicopathologic features and clinical outcomes. The p-values for survival analyses were corrected for multiple testing (threshold 0.01). Results Most tumors expressed CK5/6 (73%), EGFR (59%), CD44 (81%), and vimentin (87%). Eighty-nine percent had a high Ki-67 index. Eighty-four percent were classified as basal-like (CK 5/6 or EGFR positive). AR was expressed in 21% of the tumors. The basal-like phenotype was significantly (p = 0.009) associated with inferior disease-free (DFS) and breast-cancer-specific overall survival (BCOS) with borderline significance (p = 0.01). In addition, a low Ki-67 index was associated with improved DFS (p = 0.033) and BCOS (p = 0.03). Conclusion Most MpBCs express basal markers (CK5/6, EGFR), epithelial-mesenchymal transition marker vimentin, and the stem cell marker CD44. Expression of basal-like markers was significantly related to inferior DFS. All the 11 patients with a lack of expression of basal markers survived without relapse.Peer reviewe

Resection margins and local recurrences of impalpable breast cancer : Comparison between radioguided occult lesion localization (ROLL) and radioactive seed localization (RSL)

Objectives: The aim of this retrospective study is to compare surgical margins, reoperation rates and local recurrences after breast conserving surgery (BCS) using radioguided occult lesion localization (ROLL) or radioactive seed localization (RSL). Materials and methods: We reviewed 744 consecutive patients with impalpable primary invasive breast cancer who underwent BCS at Helsinki University Hospital between 2010 and 2012. ROLL was used in our unit until October 31st, 2011; from November 1st we changed localization method to RSL. Results: 318 patients underwent ROLL and 426 RSL. Patients in the RSL group had more often multifocal (p = 0.013) tumours. No statistically significant differences were found regarding tumour size, specimen weight, histology or grade of tumours or lymph node status. 42 (5.6%) patients were reoperated because of insufficient margins, 13 (4.1%) in the ROLL group and 29 (6.8%) in the RSL group. The reoperation rate was not different between the groups either in the univariable analysis (p = 0.112) or in the multivariable binary logistic regression analysis (p = 0.204). Risk factors for reoperations were multifocality of the tumour (p Conclusion: Reoperation rates and LRFS were comparable for ROLL and RSL in patients with impalpable breast cancer treated with BCS. (C) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Family history influences the tumor characteristics and prognosis of breast cancers developing during postmenopausal hormone therapy

Long term use of postmenopausal hormone therapy (HT) has been reported to increase breast cancer risk. On the other hand, observational studies suggest that breast cancers diagnosed during HT may have a more favorable prognosis. While family history is a risk factor for breast cancer, and genetic factors also influence prognosis, the role of family history in combination with HT use has been little studied. We investigated the relationship between HT, family history, and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial breast cancer cases, using three survival end points: death from breast cancer (BCS), distant disease free survival (DDFS), and local recurrence free survival (LRFS). Among non-familial cases, HT was associated with better BCS (HR 0.63, 95% CI 0.41-0.94; p = 0.025), and DDFS (HR 0.58, 95% CI 0.40-0.85; p = 0.005), with a consistent but not statistically significant effect in LRFS. This effect was not seen in familial cases (HR > 1.0), and family history was found to interact with HT in BCS (p((interaction)) = 0.0067) (BC-death) and DDFS (p((interaction)) = 0.0070). There was phenotypic heterogeneity between HT-associated tumors in familial and non-familial cases, particularly on estrogen receptor (ER) status, although the interaction between HT and family history appears to be at least partially independent of these markers (p = 0.0370 after adjustment for standard prognostic factors). If confirmed by further studies, our results suggest that family history should be taken into consideration in clinical counseling before beginning a HT regimen.Peer reviewe

Biological subtyping of early breast cancer : a study comparing RT-qPCR with immunohistochemistry

The biological subtype of breast cancer influences the selection of systemic therapy. Distinction between luminal A and B cancers depends on consistent assessment of Ki-67, but substantial intra-observer and inter-observer variability exists when immunohistochemistry (IHC) is used. We compared RT-qPCR with IHC in the assessment of Ki-67 and other standard factors used in breast cancer subtyping. RNA was extracted from archival breast tumour tissue of 769 women randomly assigned to the FinHer trial. Cancer ESR1, PGR, ERBB2 and MKI67 mRNA content was quantitated with an RT-qPCR assay. Local pathologists assessed ER, PgR and Ki-67 expression using IHC. HER2 amplification was identified with chromogenic in situ hybridization (CISH) centrally. The results were correlated with distant disease-free survival (DDFS) and overall survival (OS). qPCR-based and IHC-based assessments of ER and PgR showed good concordance. Both low tumour MKI67 mRNA (RT-qPCR) and Ki-67 protein (IHC) levels were prognostic for favourable DDFS [hazard ratio (HR) 0.42, 95 % CI 0.25-0.71, P = 0.001; and HR 0.56, 0.37-0.84, P = 0.005, respectively] and OS. In multivariable analyses, cancer MKI67 mRNA content had independent influence on DDFS (adjusted HR 0.51, 95 % CI 0.29-0.89, P = 0.019) while Ki-67 protein expression had not any influence (P = 0.266) whereas both assessments influenced independently OS. Luminal B patients treated with docetaxel-FEC had more favourable DDFS and OS than those treated with vinorelbine-FEC when the subtype was defined by RT-qPCR (for DDFS, HR 0.52, 95 % CI 0.29-0.94, P = 0.031), but not when defined using IHC. Breast cancer subtypes approximated with RT-qPCR and IHC show good concordance, but cancer MKI67 mRNA content correlated slightly better with DDFS than Ki-67 expression. The findings based on MKI67 mRNA content suggest that patients with luminal B cancer benefit more from docetaxel-FEC than from vinorelbine-FEC.Peer reviewe

Myofibroblastic cell activation and neovascularization predict native liver survival and development of esophageal varices in biliary atresia

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Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells

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Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines : Implications for Pandemrix-Associated Narcolepsy Risk

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AS03 Adjuvanted AH1N1 Vaccine Associated with an Abrupt Increase in the Incidence of Childhood Narcolepsy in Finland

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Increased Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland

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