Prevalence and risk of colorectal neoplasia in consumers of alcohol in a screening population

BACKGROUND AND AIMS: Although studies suggest a positive association between alcohol consumption and risk for colorectal neoplasia, the impact on screening has not been fully examined. It is also unclear whether all types of alcohol are associated with an increased risk. We performed a cross-sectional study to examine the impact of regular alcohol consumption on the detection of significant colorectal neoplasia in a screening population. METHODS: Data collected for 2,291 patients presenting for screening colonoscopy: known risk factors for colorectal neoplasia and alcohol drinking pattern. Our outcome was the endoscopic detection of significant colorectal neoplasia, which included adenocarcinoma, high-grade dysplasia, villous tissue, adenomas 1 cm or greater and multiple (>2) adenomas of any size. RESULTS: When compared to abstainers, we found an increased risk for significant neoplasia in those patients who consumed more than eight drinks of spirits alcohol (26.3%; OR = 2.53; 95% CI = 1.10-4.28; p < 0.01) and those who drank more than eight servings of beer per week (21.7%; OR = 2.43; 95% CI = 1.11-5.32; p= 0.02). Consuming one to eight glasses of wine per week was associated with a decreased risk for significant neoplasia (OR = 0.55; 95% CI = 0.34-0.87; p < 0.01). CONCLUSIONS: While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.     

Angiogenesis promoted by vascular endothelial growth factor: Regulation through α1β1 and α2β1 integrins

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a cytokine of central importance for the angiogenesis associated with cancers and other pathologies. Because angiogenesis often involves endothelial cell (EC) migration and proliferation within a collagen-rich extracellular matrix, we investigated the possibility that VEGF promotes neovascularization through regulation of collagen receptor expression. VEGF induced a 5- to 7-fold increase in dermal microvascular EC surface protein expression of two collagen receptors—the α₁β₁ and α₂β₁ integrins—through induction of mRNAs encoding the α₁ and α₂ subunits. In contrast, VEGF did not induce increased expression of the α₃β₁ integrin, which also has been implicated in collagen binding. Integrin α₁-blocking and α₂-blocking antibodies (Ab) each partially inhibited attachment of microvascular EC to collagen I, and α₁-blocking Ab also inhibited attachment to collagen IV and laminin-1. Induction of α₁β₁ and α₂β₁ expression by VEGF promoted cell spreading on collagen I gels which was abolished by a combination of α₁-blocking and α₂-blocking Abs. In vivo, a combination of α₁-blocking and α₂-blocking Abs markedly inhibited VEGF-driven angiogenesis; average cross-sectional area of individual new blood vessels was reduced 90% and average total new vascular area was reduced 82% without detectable effects on the pre-existing vasculature. These data indicate that induction of α₁β₁ and α₂β₁ expression by EC is an important mechanism by which VEGF promotes angiogenesis and that α₁β₁ and α₂β₁ antagonists may prove effective in inhibiting VEGF-driven angiogenesis in cancers and other important pathologies.     

Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD

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Is Going Beyond Rasch Analysis Necessary to Assess the Construct Validity of a Motor Function Scale?

Objective

To examine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity.

Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae

Purpose

To investigate the clinical significance of infection-related ventilator-associated complications (IVAC) and their impact on carbapenem consumption in mechanically ventilated (MV) patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE).

Methods

Inception cohort study from the French prospective multicenter OUTCOMEREA database (17 ICUs, 1997–2015) including all ESBLE carriers (systematic rectal swabbing at admission then weekly and/or urinary or superficial surgical site colonisation) with MV duration?>?48 h and?≥?1 episode of IVAC after carriage documentation. All ICU-acquired infections were microbiologically documented.

Results

The 318 enrolled ESBLE carriers (median age 68 years; males 67%; medical admission 68%; imported carriage 53%) experienced a total of 576 IVAC comprising 361 episodes (63%) without documented infection, 124 (21%) related to infections other than ventilator-associated pneumonia (VAP), 73 (13%) related to non-ESBLE VAP and 18 (3%) related to ESBLE VAP. Overall, ESBLE infections accounted for only 43 episodes (7%). Carbapenem exposure within the preceding 3 days was the sole independent predictor of ESBLE infection as the causative event of IVAC, with a protective effect (adjusted odds ratio 0.2, 95% confidence interval 0.05–0.6; P?<?0.01). Carbapenems were initiated in 9% of IVAC without infection, 15% of IVAC related to non-VAP infections, 42% of IVAC related to non-ESBLE VAP, and 56% of IVAC related to ESBLE VAP (ESBLE VAP versus non-ESBLE VAP: P?=?0.43).

Conclusions

IVAC in ESBLE carriers mostly reflect noninfectious events but act as a strong driver of empirical carbapenem consumption. ESBLE infections are scarce yet hard to predict, strengthening the need for novel diagnostic approaches and carbapenem-sparing alternatives.

     

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients

Clinical Rheumatology - IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the...     

Outcomes of pregnancy in women with tetralogy of Fallot

OBJECTIVES: We sought to determine pregnancy outcomes in patients with tetralogy of Fallot (TOF). BACKGROUND: Pregnancy outcomes in patients with TOF are incompletely defined. METHODS: Clinical, hemodynamic, and obstetric data were reviewed for women with TOF and prior pregnancy. RESULTS: Of 72 respondents, 43 (mean age, 26 years) had 112 pregnancies (range, 1 to 5); 82 pregnancies were successful. Eight women had unrepaired TOF at the time of their 20 successful pregnancies. At first assessment (age > or =18 years), six patients had pulmonary hypertension, three had moderate or severe right ventricular (RV) systolic dysfunction, and 13 had severe RV dilation due to pulmonic regurgitation. Sixteen patients had 30 miscarriages (27%) and one term stillbirth. Mean overall birth weight was 3.2 kg (range, 2.1 to 4.2 kg). Unrepaired TOF (p = 0.05) and morphologic pulmonary artery abnormality (p = 0.03) were independently predictive of infant birth weight. Six patients had cardiovascular complications during pregnancy: supraventricular tachycardia in two, heart failure in two, pulmonary embolism in a patient with pulmonary hypertension, and progressive RV dilation in a patient with severe pulmonic regurgitation. Five infants (6%) had congenital anomalies. CONCLUSIONS: Patients with TOF have an increased risk of fetal loss, and their offspring are more likely to have congenital anomalies than offspring in the general population. Adverse maternal events, although rare, may be associated with left ventricular dysfunction, severe pulmonary hypertension, and severe pulmonic regurgitation with RV dysfunction.