S Maria Annunziata Hospital

Firenze, Italy

S Maria Annunziata Hospital

Firenze, Italy

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Mazzoni F.,Azienda Ospedaliero Universitaria Careggi | Cecere F.L.,Azienda Ospedaliero Universitaria Careggi | Meoni G.,Azienda Ospedaliero Universitaria Careggi | Giuliani C.,Azienda Ospedaliero Universitaria Careggi | And 8 more authors.
Lung Cancer | Year: 2013

Objectives: Customized chemotherapy has several advantages: patients are more likely to be treated with the most effective agents and can be spared the toxicity of ineffective drugs. Based on the literature, excision repair cross complementation group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) genes represent predictive biomarkers of response to platinum compound and gemcitabine, in NSCLC. Materials and methods: We had planned a phase II trial (Simon design) to evaluate combination chemotherapy according to single nucleotide polymorphisms (SNPs) of ERCC1 (118T/C and 8092C/A) and RRM1 (-37C/A and -524T/C) in naïve patients affected by advanced NSCLC. ERCC1 and RRM1 SNPs assessment was performed in peripheral blood lymphocytes (PBLs). Combination chemotherapy was selected based on ERCC1 and RRM1 SNPs: we assume that patients with one or two C alleles at position 118 and with one or two A alleles at position 8092 in ERCC1 gene would correspond to Cisplatin non-responder and than with two A alleles at -37 and two C alleles at -524 in RRM1 gene to gemcitabine non-responder. Four schedules were provided: cisplatin. +. gemcitabine, cisplatin. +. docetaxel, gemcitabine. +. docetaxel; docetaxel. +. vinorelbine. Primary endpoint was overall response (ORR) in the intention-to-treat population. Results: 42 patients were enrolled from January 2010 to November 2011; 40 patients received at least 1 cycle of chemotherapy; median age was 66 years (range: 47-72); 36(90%) had stage IV, 4(10%) IIIB; 23(58%) had adenocarcinoma, 14(35%) squamous carcinoma. Twenty-five (62%) patients received treatment A, 3(8%) treatment B, 11(28%) treatment C, 1(23%) treatment D. ORR was 55%, analysis in squamous patients subgroups showed 71.4% ORR. The median follow-up was 19.7 months, PFS was 23 weeks (95% CI = 15-26) and OS was 40.4 weeks (95% CI = 32-55). Treatment was well tolerated. Conclusion: We observed an increase of ORR in NSCLC patients when they were treated with chemotherapy according to ERCC1 and RRM1 SNPs status. © 2013 Elsevier Ireland Ltd.


Forni D.,Scientific Institute Irccs E Medea | Cagliani R.,Scientific Institute Irccs E Medea | Tresoldi C.,Scientific Institute Irccs E Medea | Pozzoli U.,Scientific Institute Irccs E Medea | And 14 more authors.
PLoS Genetics | Year: 2014

The antigenic repertoire presented by MHC molecules is generated by the antigen processing and presentation (APP) pathway. We analyzed the evolutionary history of 45 genes involved in APP at the inter- and intra-species level. Results showed that 11 genes evolved adaptively in mammals. Several positively selected sites involve positions of fundamental importance to the protein function (e.g. the TAP1 peptide-binding domains, the sugar binding interface of langerin, and the CD1D trafficking signal region). In CYBB, all selected sites cluster in two loops protruding into the endosomal lumen; analysis of missense mutations responsible for chronic granulomatous disease (CGD) showed the action of different selective forces on the very same gene region, as most CGD substitutions involve aminoacid positions that are conserved in all mammals. As for ERAP2, different computational methods indicated that positive selection has driven the recurrent appearance of protein-destabilizing variants during mammalian evolution. Application of a population-genetics phylogenetics approach showed that purifying selection represented a major force acting on some APP components (e.g. immunoproteasome subunits and chaperones) and allowed identification of positive selection events in the human lineage.We also investigated the evolutionary history of APP genes in human populations by developing a new approach that uses several different tests to identify the selection target, and that integrates low-coverage whole-genome sequencing data with Sanger sequencing. This analysis revealed that 9 APP genes underwent local adaptation in human populations. Most positive selection targets are located within noncoding regions with regulatory function in myeloid cells or act as expression quantitative trait loci. Conversely, balancing selection targeted nonsynonymous variants in TAP1 and CD207 (langerin). Finally, we suggest that selected variants in PSMB10 and CD207 contribute to human phenotypes. Thus, we used evolutionary information to generate experimentally-testable hypotheses and to provide a list of sites to prioritize in follow-up analyses. © 2014 Forni et al.


Cameli M.,University of Siena | Lisi M.,University of Siena | Mondillo S.,University of Siena | Padeletti M.,University of Siena | And 4 more authors.
Cardiovascular Ultrasound | Year: 2010

Background. The combination of early transmitral inflow velocity and mitral annular tissue Doppler imaging (E/Em ratio) is widely applied to noninvasively estimate left ventricular (LV) filling pressures. However E/Em ratio has a significant gray zone and its accuracy in patients with heart failure is debated. Left atrial (LA) deformation analysis by speckle tracking echocardiography (STE) was recently proposed as an alternative approach to estimate LV filling pressures. This study aimed at exploring the correlation of LA longitudinal function by STE and Doppler measurements with direct measurements of LV filling pressures in patients with heart failure. Methods. A total of 36 patients with advanced systolic heart failure (ejection fraction ≤35%), undergoing right heart catheterization, were studied. Simultaneously to pulmonary capillary wedge pressure (PCWP) determination, peak atrial longitudinal strain (PALS) and mean E/Em ratio were measured in all subjects by two independent operators. PALS values were obtained by averaging all segments (global PALS), and by separately averaging segments measured in the 4-chamber and 2-chamber views. Results. Not significant correlation was found between mean E/Em ratio and PCWP (R = 0.15). A close negative correlation between global PALS and the PCWP was found (R = -0.81, p < 0.0001). Furthermore, global PALS demonstrated the highest diagnostic accuracy (AUC of 0.93) and excellent sensitivity and specificity of 100% and 93%, respectively, to predict elevated filling pressure using a cutoff value less than 15.1%. Bland-Altman analysis confirmed this close agreement between PCWP estimated by global PALS and invasive PCWP (mean bias 0.1±8.0 mmHg). Conclusion. In a group of patients with advanced systolic heart failure, E/Em ratio correlated poorly with invasively obtained LV filling pressures. However, LA longitudinal deformation analysis by STE correlated well with PCWP, providing a better estimation of LV filling pressures in this particular clinical setting. © 2010 Cameli et al; licensee BioMed Central Ltd.


Cameli M.,University of Siena | Ballo P.,S Maria Annunziata Hospital | Righini F.M.,University of Siena | Caputo M.,University of Siena | And 2 more authors.
Echocardiography | Year: 2011

Background: The associations of left ventricular (LV) systolic torsion with clinical and echocardiographic variables in physiological conditions have not been fully investigated. We explored the independent determinants of LV systolic torsion in a population of normal subjects. Methods: In 119 healthy subjects, peak twist angle (LVtw) and torsion (LVtor) during ejection, and the QRS-LVtw interval (time-to-peak LVtw) were measured by speckle tracking. LV twisting rate and rotational deformation delay were also determined. Results: Stepwise multiple regression showed that LVtw was independently associated with indexed end-systolic volume (β=-0.200, P < 0.0001), peak early diastolic mitral annulus velocity (β=-0.186, P = 0.0001), heart rate (β= 0.178, P = 0.0003), and male gender (β=-0.174, P = 0.0004). Similar results were found for LVtor. Age was the only parameter, which has demonstrated an independent correlation with time-to-peak LVtw (β= 0.329, P < 0.0001). Despite significance of these associations, the proportions of variability explained by regression models were relatively low (range 11-26%), and no accurate predictive models were identifiable for LV twisting rate and rotational deformation delay. Conclusion: In normal individuals, indexed end-systolic LV volume, LV relaxation, heart rate, gender, and age correlate independently with LV torsion mechanics. However, conventional echocardiographic and clinical variables are not able to predict LV torsion mechanics. © 2011, Wiley Periodicals, Inc.


Bocelli A.,A Meyer Hospital | Favilli S.,A Meyer Hospital | Pollini I.,A Meyer Hospital | Bini R.M.,A Meyer Hospital | And 3 more authors.
Pediatric Cardiology | Year: 2013

Controversial data exist about the long-term results of aortic coarctation (AC) repair. This study explored the prevalence and predictors of left ventricular (LV) hypertrophy, late hypertension, and hypertensive response to exercise in 48 subjects (age, 15.1 ± 9.7 years) currently followed in the authors' tertiary care hospital after successful AC repair. Data on medical history, clinical examination, rest and exercise echocardiography, and ambulatory blood pressure monitoring were collected. The time from AC repair to follow-up evaluation was 12.9 ± 9.2 years. The prevalence of LV hypertrophy ranged from 23 to 38 %, based on the criteria used to identify LV hypertrophy, and that of concentric geometry was 17 %. One sixth of the patients without residual hypertension experienced late-onset hypertension. One fourth of those who remained normotensive without medication showed a hypertensive response to exercise. Age at AC repair was the strongest independent predictor of LV hypertrophy, defined using indexation either for body surface area (odds ratio [OR], 1.03; p = 0.0090) or for height2.7 (OR 1.02; p = 0.029), and it was the only predictor of late hypertension (OR 1.06; p = 0.0023) and hypertensive response to exercise (OR 1.09; p = 0.029). The risk of LV hypertrophy was 25 % for repair at the age of 3.4 years but rose to 50 and 75 % for repair at the ages of 5.9 and 8.4 years, respectively. Similar increases were found for the risk of late-onset hypertension and hypertensive response to exercise. A considerable risk of LV hypertrophy, late hypertension, and hypertensive response to exercise exists after successful AC repair. Older age at intervention is the most important predictor of these complications. © 2012 Springer Science+Business Media, LLC.


Cameli M.,University of Siena | Lisi M.,University of Siena | Righini F.M.,University of Siena | Tsioulpas C.,University of Siena | And 6 more authors.
Journal of Cardiac Failure | Year: 2012

Background: Right ventricular (RV) systolic function has a critical role in determining the clinical outcome and success of using left ventricular assist devices (LVADs) in patients with refractory heart failure. Tissue Doppler and M-mode measurements of tricuspid systolic motion (tricuspid S′ and tricuspid annular plane systolic excursion [TAPSE]) are the most currently used methods for the quantification of RV longitudinal function; RV deformation analysis by speckle-tracking echocardiography (STE) has recently allowed the analysis of global RV longitudinal function. Using cardiac catheterization as the reference standard, this study aimed at exploring the correlation between RV longitudinal function by STE and RV stroke work index (RVSWI) in patients referred for cardiac transplantation. Methods and Results: Right-side heart catheterization and transthoracic echo Doppler were simultaneously performed in 41 patients referred for cardiac transplantation evaluation for advanced systolic heart failure. Thermodilution RV stroke volume and invasive pulmonary pressures were used to obtain RVSWI. RV longitudinal strain (RVLS) by STE was assessed averaging all segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall segments (free-wall RVLS). Tricuspid S′ and TAPSE were also calculated. No significant correlations were found for TAPSE or tricuspid S′ with RVSWI (r = 0.14; r = 0.06; respectively). Close negative correlations between global RVLS and free-wall RVLS with the RVSWI were found (r = -0.75; r = -0.82; respectively; both P <.0001). Furthermore, free-wall RVLS demonstrated the highest diagnostic accuracy (area under the receiver operating characteristic (ROC) curve 0.90) and good sensitivity and specificity of 92% and 86%, respectively, to predict depressed RVSWI using a cutoff value of less than -11.8%. Conclusions: In a group of patients referred for heart transplantation, TAPSE and tricuspid S′ did not correlate with invasively obtained RVSWI. RV longitudinal deformation analysis by STE correlated well with RVSWI, providing a better estimation of RV systolic performance. © 2012 Elsevier Inc. All rights reserved.


Ballo P.,S Maria Annunziata Hospital | Betti I.,S Maria Annunziata Hospital | Barchielli A.,Epidemiology Unit | Castelli G.,Careggi Hospital | And 3 more authors.
Obesity | Year: 2013

Objective The existence of an "obesity paradox" in asymptomatic patients with preclinical heart failure (HF) has not been investigated. The prognostic value of BMI in a cohort of hypertensive and diabetic patients with stage A/B HF enrolled in the PROBE-HF study was explored. Design and Methods BMI was measured in 1003 asymptomatic subjects (age 66.4 ± 7.8 years, 48% males) with hypertension and/or type 2 diabetes and no clinical evidence of HF. Predefined endpoints were all-cause mortality and a composite of death and hospitalization for cardiac causes. Results During a follow-up of 38.5 ± 4.1 months, 33 deaths were observed. Mortality in the normal BMI group (1.6 deaths per 100 patient-years) did not differ to that in the overweight group (1.1 per 100 patient-years, p = 0.31), but was higher than that in the obese group (0.4 per 100 patient-years, p = 0.0089). In multivariable analysis, obesity (hazard ratio [HR] 0.27 [0.09-0.85], p = 0.025) but not overweight (HR 0.68 [0.32-1.45], p = 0.32) was associated with lower risk of death. Obesity was also independently associated with reduced risk of the composite endpoint (HR 0.54 [0.28-0.99], p = 0.047). Conclusion In asymptomatic hypertensive and diabetic patients with preclinical HF, obesity is associated with better survival and reduced risk of events. Copyright © 2013 The Obesity Society.


Mondillo S.,University of Siena | Cameli M.,University of Siena | Caputo M.L.,University of Siena | Lisi M.,University of Siena | And 3 more authors.
Journal of the American Society of Echocardiography | Year: 2011

Background: Systemic hypertension and type 2 diabetes mellitus are associated with impaired left atrial (LA) function, but whether LA functional abnormalities also occur in patients with hypertension and diabetes who have normal LA sizes is unknown. The aim of this study was to explore LA strain using speckle-tracking echocardiography in patients with hypertension or diabetes and normal LA size. Methods: LA strain was studied by speckle-tracking echocardiography in 155 patients with hypertension or diabetes with LA volume indexes < 28 mL/m 2 (83 with hypertension, 34 with diabetes, and 38 with both diabetes and hypertension) and 36 age-matched controls. The following indexes were measured: peak atrial longitudinal strain, time to peak atrial longitudinal strain, atrial longitudinal strain during early diastole and late diastole, and peak LA strain rate during ventricular systole, early diastole, and late diastole. Results: Peak atrial longitudinal strain was lower in patients with hypertension (29.0 ± 6.5%) and those with diabetes (24.7 ± 6.4%) than in controls (39.6 ± 7.8%) and further reduced in patients with diabetes and hypertension (18.3 ± 5.0%) (P <.0001). Similar results were found for atrial longitudinal strain during early diastole, atrial longitudinal strain during late diastole, and peak LA strain rate during ventricular systole and early diastole (P <.0001 for all). An inverse trend was found for time to peak atrial longitudinal strain, whereas no differences in peak LA strain rate during late diastole were observed. Two-way analysis of variance showed no interactions between hypertension and diabetes. In multivariate analyses, hypertension and diabetes were both independently associated with decreases in all LA strain and strain rate indexes, with the exception of peak LA strain rate during late diastole. Conclusions: LA deformation mechanics are impaired in patients with hypertension or diabetes with normal LA size. The coexistence of both conditions further impairs LA performance in an additive fashion. Speckle-tracking echocardiography may be considered a promising tool for the early detection of LA strain abnormalities in these patients. © 2011 by the American Society of Echocardiography.


Ballo P.,S Maria Annunziata Hospital | Nistri S.,Cardiology Service | Cameli M.,University of Siena | Papesso B.,Cardiology Service | And 4 more authors.
Journal of Cardiac Failure | Year: 2014

Background The relationships of left ventricular (LV) longitudinal and circumferential systolic dysfunction with diastolic performance in hypertensive patients have never been compared. Methods and Results In 532 asymptomatic hypertensive patients, circumferential function was assessed with the use of midwall fractional shortening (mFS) and stress-corrected mFS (SCmFS), whereas longitudinal function was assessed with the use of left atrioventricular plane displacement (AVPD) and systolic mitral annulus velocity (s′). Early diastolic annular velocity (e′) and the E/e′ ratio were measured. Global longitudinal and circumferential strain were determined in a subset of 210 patients. e′ was linearly related to all systolic indexes (AVPD: R = 0.40; s′: R = 0.39; mFS: R = 0.16; SCmFS: R = 0.17; all P <.0001), but the correlations were stronger with longitudinal indexes than with circumferential ones (P <.0001). E/e′ was nonlinearly related to AVPD (R = -0.49; P <.0001) and s′ (R = -0.34; P <.0001) and showed no relationship with mFS and SCmFS. Longitudinal indexes were superior to circumferential ones in predicting e′ <8 cm/s, E/e′ <8, and E/e′ ≥13. The effect of LV geometry on LV diastolic function was evident among patients with preserved systolic longitudinal function, but was blunted among patients with impaired longitudinal function. In multivariable analyses, only longitudinal indexes remained associated with e′ and E/e′. Analyses using strains provided similar results. Conclusions In asymptomatic hypertensive subjects, LV diastolic performance is independently associated with longitudinal systolic dysfunction, but not with circumferential systolic dysfunction. Subtle longitudinal systolic impairment plays a role in mediating the effect of LV geometry on diastolic performance. These findings may support the need of critically revising the concept of isolated diastolic dysfunction in these patients. © 2014 Elsevier Inc. All rights reserved.


PubMed | S Maria Annunziata Hospital
Type: | Journal: Case reports in medicine | Year: 2017

Left atrial invasion by lung cancer via haematogenous pathways is a relatively uncommon but potentially life-threatening event. While several cardiac complications of cardiac involvement have been previously described, the evolution towards cerebral stroke has been rarely reported. In this case report, we describe an atypical case of haematogenous metastatic invasion of the left atrium from pulmonary neoplasm extension presenting as an ipsilateral stroke whose ASCO classification changed during the clinical management.

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