A Quantitative Assessment of Cerebral Hemodynamic Perturbations Associated with Long R-R Intervals in Atrial Fibrillation: A Pilot-Case-Based Experience

Background and Objectives: Atrial fibrillation (AF) results in systemic hemodynamic perturbations which impact cerebral circulation, possibly contributing to the development of dementia. However, evidence documenting effects in cerebral perfusion is scarce. The aim of this study is to provide a quantitative characterization of the magnitude and time course of the cerebral hemodynamic response to the short hypotensive events associated with long R-R intervals, as detected by near-infrared spectroscopy (NIRS). Materials and Methods: Cerebral NIRS signals and arterial blood pressure were continuously recorded along with an electrocardiogram in twelve patients with AF undergoing elective electrical cardioversion (ECV). The top 0.5-2.5% longest R-R intervals during AF were identified in each patient and used as triggers to carry out the triggered averaging of hemodynamic signals. The average curves were then characterized in terms of the latency, magnitude, and duration of the observed effects, and the possible occurrence of an overshoot was also investigated. Results: The triggered averages revealed that long R-R intervals produced a significant drop in diastolic blood pressure (-13.7 ± 6.1 mmHg) associated with an immediate drop in cerebral blood volume (THI: -0.92 ± 0.46%, lasting 1.9 ± 0.8 s), followed by a longer-lasting decrease in cerebral oxygenation (TOI: -0.79 ± 0.37%, lasting 5.2 ± 0.9 s, p < 0.01). The recovery of the TOI was generally followed by an overshoot (+1.06 ± 0.12%). These effects were progressively attenuated in response to R-R intervals of a shorter duration. Conclusions: Long R-R intervals cause a detectable and consistent cerebral hemodynamic response which concerns both cerebral blood volume and oxygenation and outlasts the duration of the systemic perturbation. These effects are compatible with the activation of dynamic autoregulatory mechanisms in response to the hypotensive stimulus

Long‐term outcomes of phenoclusters in preclinical heart failure with preserved and mildly reduced ejection fraction

Aims The identification of subjects at higher risk for incident heart failure (HF) with preserved ejection fraction (EF) suitable for more intensive preventive programmes remains challenging. We applied phenomapping to the DAVID-Berg population, comprising subjects with preclinical HF, aiming to refine HF risk stratification. Methods The DAVID-Berg study prospectively enrolled 596 asymptomatic outpatients with EF &gt; 40% with hypertension, diabetes mellitus or known cardiovascular disease. In this cohort, we performed an unsupervised cluster analysis on 591 patients, including clinical, laboratory, electrocardiographic and echocardiographic parameters. We tested the association between each cluster and a composite outcome of HF/death. Results The median age was 70 years, 55.5% were males and the median EF was 61.0%. Phenomapping provided three different clusters. Subjects in Cluster 3 were the oldest and had the highest prevalence of atrial fibrillation, the lowest estimated glomerular filtration rate (eGFR), the highest N-terminal pro-brain natriuretic peptide (NT-proBNP) and the largest left atrium. During a median follow-up of 5.7 years, 13.4% of subjects experienced HF/death events (N = 79). Compared with Clusters 1 and 2, Cluster 3 had the worst prognosis (log-rank test: Cluster 3 vs. 1 P &lt; 0.001; Cluster 3 vs. 2 P = 0.008). Cluster 3 was associated with a risk of HF/death 2.5 times higher than Cluster 1 [adjusted hazard ratio (HR) = 2.46, 95% confidence interval (CI) 1.24-4.90]. Conclusions Based on phenomapping, older patients with lower kidney function and worse diastolic function might represent a subset of preclinical HF with EF &gt; 40% who deserve more efforts to prevent clinical HF

Stima della prevalenza di broncopneumopatia cronico-ostruttiva basata su dati sanitari correnti, mediante l\u27uso di un algoritmo comune, in differenti aree italiane

Aim: to estimate the prevalence of chronic obstructive pulmonary disease (COPD) by integrating various administrative health information systems. Methods: prevalent COPD cases were defined as those reported in the hospital discharge registry (HDR) and cause of mortality registry (CMR) with codes 490*, 491*, 492*, 494* e 496* of the International diseases classification 9th revision. Annual prevalence was estimated in 35+ year-old residents in six Italian areas of different sizes, in the period 2002-2004. We in- Annunziata Faustini,1 Silvia Cascini,1 Massimo Arc?,1 Daniela Balzi,2 Alessandro Barchielli,2 Cristina Canova,3 Claudia Galassi,4 Enrica Migliore,4,5 Sante Minerba,6 Maria Angela Protti,7 Anna Romanelli,7 Roberta Tessari,3,8 Maria Angela Vigotti,9 Lorenzo Simonato3 1Dipartimento di epidemiologia, ASL RME, Roma 2Unit? operativa di epidemiologia, Azienda sanitaria 10, Firenze 3Dipartimento di medicina ambientale e sanit? pubblica, Universit? di Padova 4Servizio di epidemiologia dei tumori, ASO S. Giovanni Battista, CPO Piemonte e Universit? di Torino 5Unit? di pneumologia, CPA-ASL TO2, Torino 6Unit? di statistica ed epidemiologia, ASL 1 Taranto 7Sezione di epidemiologia e ricerca sui servizi sanitari, IFC-CNR, Pisa 8Unit? di epidemiologia, Dipartimento di prevenzione, Azienda ULSS 12 Veneziana 9Dipartimento di biologia, Universit? di Pisa Corrispondenza: Annunziata Faustini, Dipartimento di epidemiologia, ASL RME, via Santa Costanza 53, 00198 Roma; tel. 06 86060486; fax 06 86060463; e-mail [email protected] cluded cases observed in the previous four years who were alive at the beginning of each year. Results: in 2003, age-standardized prevalence rates varied from 1.6% in Venice to 5% in Taranto. Prevalence was higher in males and increased with age. The highest rates were observed in central (Rome) and southern (Taranto) cities, especially in the 35-64 age group. HDR contributed 91% of cases. Healthtax exemption registry would increase the prevalence estimate by 0.2% if used as a third data source. Conclusions: with respect to the National Health Status suraldelvey, COPD prevalence is underestimated by 1%-3%; this can partly be due to the selection of severe and exacerbated COPD by the algorithm used. However, age, gender and geographical characteristics of prevalent cases were comparable to national estimates. Including cases observed in previous years (longitudinal estimates) increased the point estimate (yearly) of prevalence two or three times in each area.Obiettivi: stimare la prevalenza della broncopneumopatia cronico-ostruttiva (BPCO) mediante l\u27utilizzo integrato di dati sanitari correnti. Metodi: la prevalenza ? stata stimata nella popolazione residente di et? superiore ai 34 anni, in sei aree geografiche, per gli anni 2002-2004. I casi prevalenti sono stati individuati dai registri delle schede di dimissione ospedaliera (SDO) e delle cause di morte (RCM), mediante i codici ICD9-CM 490*, 491*, 492*, 494* e 496* della Classificazione internazionale delle malattie 9? revisione (ICD9-CM). Ai casi osservati in ciascun anno sono stati aggiunti i pazienti ricoverati nei quattro anni precedenti e vivi all\u27inizio dell\u27anno di stima. Risultati: la prevalenza della BPCO, stimata mediante tassi standardizzati per et?, varia per il 2003 dall\u271,6% di Venezia sural 5% di Taranto. La prevalenza ? pi? alta negli uomini e aumenta con l\u27et?; Taranto e Roma presentano i valori pi? elevati, specialmente nelle classi d\u27et? dai 35 ai 64 anni. Fonte principale dei casi sono i ricoveri ospedalieri, con un contributo di almeno il 91%. L\u27uso delle esenzioni ticket come terza fonte incrementa la stima di prevalenza dello 0,2%. Conclusioni: la prevalenza della BPCO ? sottostimata dell\u271%-3% rispetto ai dati dell\u27indagine Istat sullo stato di salute; questo ? in parte attribuibile alla selezione dei casi medio- gravi da parte dell\u27algoritmo utilizzato. Tuttavia le stime mantengono le caratteristiche attese nella distribuzione per genere, et? e area geografica. Inoltre, l\u27uso longitudinale dei dati ospedalieri aumenta di 2-3 volte la stima di prevalenza basata sui dati dei singoli anni

Plasma miR-151-3p as a Candidate Diagnostic Biomarker for Head and Neck Cancer: A Cross-sectional Study within the INHANCE Consortium

Background: Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium. Methods: A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test. Results: We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls. Conclusions: We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status. Impact: The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Background: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. Patients and methods: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. Results: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR=2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR=1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR=2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity ( &gt; 20 cigarettes/day HR=1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. Conclusions: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients

Genetic Contributions to the Association between Adult Height and Head and Neck Cancer : A Mendelian Randomization Analysis

Acknowledgements: The authors thank the Italian Association for Research on Cancer (AIRC, IG 2013 n. 14211) and the PRECeDI project (Marie Skłodowska-Curie Research and Innovation Staff Exchange - RISE N°645740) for supporting the work of Roberta Pastorino and Anna Puggina.Peer reviewedPublisher PD

Plasma miR-151-3p as a candidate diagnostic biomarker for head and neck cancer: a cross-sectional study within the INHANCE consortium

Identification of screening tests for the detection of head and neck cancer at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating microRNAs for the diagnosis of head and neck cancer (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology (INHANCE) consortium