ED-B fibronectin expression is a marker of epithelial-mesenchymal transition in translational oncology

Fibronectin is a component of the extracellular matrix that links collagen fibers to integrins on the cell's surface. The splicing isoforms, containing the ED-B domain, are not expressed in adult tissues but only in tumor stroma or during embryonic development. Fibroblasts and endothelial cells express ED-B fibronectin during angiogenesis. Also cancer cells can synthetize ED-B fibronectin, but its function in tumor growth needs to be further elucidated. We evaluated the expression of ED-B fibronectin in prostate cancer cell lines: PC3 and DU145. Using TGF-β, we induced epithelial to mesenchymal transition in culture and observed an increase of ED-B fibronectin expression. Thereafter, we evaluated the expression of ED-B fibronectin in multipotent mesangiogenic progenitor cells, and in mesenchymal stromal cells. The expression of ED-B fibronectin was much higher in mesenchymal than prostate cancer cells even after the epithelial to mesenchymal transition. Epithelial to mesenchymal transition is a key step for tumor progression contributing to the metastatic spread. Therefore, circulating cancer cells could seed into the metastatic niche taking advantage from the ED-B fibronectin that secrete their own

Age, left atrial dimension and arterial stiffness after external cardioversion of atrial fibrillation. A vascular component in arrhythmia maintenance? Results from a preliminary study.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most frequent arrhythmia in elderly patients. Aims of this study were to evaluate the predictors of arterial stiffness after external cardioversion (ECV) of AF and to establish whether a link exists between vascular properties and left atrial diameter (LAD). METHODS: We studied 33 patients (age 73 ± 12 years). After 5 h from ECV of persistent AF, an echocardiogram was recorded and arterial stiffness was evaluated with cardio-ankle vascular stiffness index (CAVI). RESULTS: In multivariate analysis (R = 0.538, p = 0.006), CAVI (mean 9.60 ± 1.63) increased with age (p = 0.018) and with an AF length ≤3 months (p = 0.022). LAD was significantly related to CAVI (p = 0.007) even after adjustment for interventricular septum thickness (p = 0.018) (R = 0.574, p = 0.002). CONCLUSIONS: In patients with AF, immediately after ECV, arterial stiffness is associated with age and AF length, and could represent an important factor for left atrium remodeling and, therefore, for AF maintenance

Psychological effects of treatment with new oral anticoagulants in elderly patients with atrial fibrillation: a preliminary report

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most common arrhythmia in elderly people, yet oral anticoagulation is underused in the aged. We tried to determine whether new oral anticoagulants (NOA) have greater psychological tolerability than warfarin. METHODS: Age-, gender-matched groups of AF patients receiving NOA (N = 15) or warfarin (N = 15) were assessed with the Anti-Clot Treatment Scale (ACTS) and the Perceived Stress Scale (PSS). RESULTS: Patients were old (81 ± 9 years). NOA group showed greater psychological satisfaction, with lower therapy-related burden (ACTS burdens: 16.3 ± 4.5 vs. 32.9 ± 10.2, p < 0.001) and higher awareness of benefits (ACTS benefits: 13.0 ± 1.3 vs. 10.8 ± 1.9, p = 0.001). Even stress was lower (PSS: 13.1 ± 4.0 vs. 17.1 ± 4.2, p = 0.013). The multivariate analysis confirmed these findings, showing that higher levels of anxiety and depression could justify more stress in warfarin patients. CONCLUSIONS: The results of this preliminary study show that NOA have an improved psychological impact compared with warfarin in elderly patients

Rate-control vs rhythm-control of atrial fibrillation in elderly patients. From new, age-oriented outcomes to a more complex management strategy

Atrial fibrillation (AF) is the most frequent arrhythmia in elderly people. Findings derived from clinical trials seem to demonstrate that a rate-control strategy of AF in aged patients improves prognosis if compared to a rhythm-control one. However, epidemiological studies concordantly show that the arrhythmia is associated to increased hospitalization and mortality rates. In last years, the proportion of patients admitted to hospital for AF has progressively increased; this trend is observed in subjects >75 and >85 years, while no change was found in younger cohorts. Importantly, in aged individuals, probably because of the loss of atrial activity, the increase of heart rate and the irregularity of RR intervals, AF begins a vicious cycle, leading from heart failure, through the compromise of functional and neurocognitive status, to overt disability, dementia and increased mortality. Evidence specifically aimed at clarifying the effects of arrhythmia management on outcomes characteristic of aged people is completely lacking. In the elderly, the question regarding the effects of a rate- or a rhythm-control strategy of AF should be considered as an aspect of a more complex strategy, addressed to reduce disability and hospitalizations, and to improve quality of life and survival

hERG1 Channels Regulate VEGF-A Secretion in Human Gastric Cancer: Clinicopathological Correlations and Therapeutical Implications

Purpose: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking. Experimental Design: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models. Results: hERG1 was positive in69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1-G2 grading, I and II tumor-node-metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments. Conclusion: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed. © 2014 American Association for Cancer Research

Course and Lethality of SARS-CoV2 Epidemic in Nursing Homes after Vaccination in Florence, Italy

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30&nbsp;days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD

National variations in perioperative assessment and surgical management of Crohn's disease: a multicentre study

Aim: Crohn's disease (CD) requires a multidisciplinary approach and surgery should be undertaken by dedicated colorectal surgeons with audited outcomes. We present a national, multicentre study, with the aim to collect benchmark data on key performance indicators in CD surgery, to highlight areas where standards of CD surgery excel and to facilitate targeted quality improvement where indicated. Methods: All patients undergoing ileocaecal or redo ileocolic resection in the participating centres for primary and recurrent CD from June 2018 to May 2019 were included. The main objective was to collect national data on hospital volume and practice variations. Postoperative morbidity was the primary outcome. Laparoscopic surgery and stoma rate were the secondary outcomes. Results: In all, 715 patients were included: 457 primary CD and 258 recurrent CD with a postoperative morbidity of 21.6% and 34.7%, respectively. Laparoscopy was used in 83.8% of primary CD compared to 31% of recurrent CD. Twenty-five hospitals participated and the total number of patients per hospital ranged from 2 to 169. Hospitals performing more than 10 primary CD procedures per year showed a higher adoption of laparoscopy and bowel sparing surgery. Conclusions: There is significant heterogeneity in the number of CD surgeries performed per year nationally in Italy. Our data suggest that high-volume hospitals perform more complex procedures, with a higher adoption of bowel sparing surgery. The rate of laparoscopy in high-volume hospitals is higher for primary CD but not for recurrent CD compared with low-volume hospitals