Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Progression From Paroxysmal to Persistent Atrial Fibrillation. Clinical Correlates and Prognosis

Objectives: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. Background: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. Methods: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. Results: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score >5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. Conclusions: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future. \ua9 2010 American College of Cardiology Foundation

Radiomic analysis to predict local response in locally advanced pancreatic cancer treated with stereotactic body radiation therapy

Purpose: Aim of this study is to assess the ability of contrast-enhanced CT image-based radiomic analysis to predict local response (LR) in a retrospective cohort of patients affected by pancreatic cancer and treated with stereotactic body radiation therapy (SBRT). Secondary aim is to evaluate progression free survival (PFS) and overall survival (OS) at long-term follow-up. Methods: Contrast-enhanced-CT images of 37 patients who underwent SBRT were analyzed. Two clinical variables (BED, CTV volume), 27 radiomic features were included. LR was used as the outcome variable to build the predictive model. The Kaplan–Meier method was used to evaluate PFS and OS. Results: Three variables were statistically correlated with the LR in the univariate analysis: Intensity Histogram (StdValue feature), Gray Level Cooccurrence Matrix (GLCM25_Correlation feature) and Neighbor Intensity Difference (NID25_Busyness feature). Multivariate model showed GLCM25_Correlation (P = 0.007) and NID25_Busyness (P = 0.03) as 2 independent predictive variables for LR. The odds ratio values of GLCM25_Correlation and NID25_Busyness were 0.07 (95%CI 0.01–0.49) and 8.10 (95%CI 1.20–54.40), respectively. The area under the curve for the multivariate logistic regressive model was 0.851 (95%CI 0.724–0.978). At a median follow-up of 30 months, median PFS was 7 months (95%CI 6-NA); median OS was 11 months (95%CI 10–22 months). Conclusions: This analysis identified a radiomic signature that correlates with LR. To confirm these results, prospective studies could identify patient sub-groups with different rates of radiation dose–response to define a more personalized SBRT approach

Preoperative radiotherapy: A paradigm shift in the treatment of breast cancer? A review of literature

The standard of care for early-stage breast cancer (BC) consists of breast-conserving surgery followed by postoperative irradiation. Recently, the concept of changing the usual sequence of treatment components in BC RT has been investigated. Potential advantages of preoperative RT in BC include a possible tumor downstaging with improved surgical cosmetic outcomes, accurate tumor site identification and better target volume delineation. Furthermore, preoperative RT could serve as a tool for treatment stratification for de-escalation of treatments in the event of pathological complete response. The present literature review analyzed the available clinical data regarding the potential impact of preoperative RT. Overall, available clinical evidence of preoperative RT in BC remains limited, deriving mostly from retrospective case series. Nevertheless, the experiences prove the feasibility of the preoperative RT approach and confirm the efficacy in almost all analyzed studies, including experiences using higher prescription RT doses or RT in combination with systemic therapy

Territori dell'abusivismo. Un progetto per uscire dall'Italia dei condoni

Il volume fa il punto sul fenomeno dell’abusivismo edilizio nel Mezzogiorno, dopo un periodo di relativo silenzio degli studiosi sul tema, e avanza alcune proposte per l’innovazione dei progetti e delle politiche a esso rivolti. Alla base ci sono le riflessioni sviluppate nell’ambito di una rete di ricerca promossa e coordinata dai tre curatori con il sostegno della Società italiana degli urbanisti. I contributi ospitati nella prima parte del libro descrivono sotto angolature diverse lo sfondo in cui le pratiche dell’abusivismo e i suoi lasciti oggi si collocano. Uno sfondo per molti aspetti mutato rispetto al quadro entro il quale maturò la politica di condono edilizio nei primi anni ottanta, che richiede uno sforzo di rielaborazione critica degli assunti, delle possibilità e delle priorità dell’azione pubblica. Nella parte centrale, quattordici casi studio esplorano le articolazioni fisiche e sociali che l’edilizia non autorizzata ha prodotto nelle regioni meridionali. Un viaggio attraverso territori in cui si intrecciano problemi irrisolti, non di rado aggravatisi nel tempo, e nuove questioni riguardanti la transizione demografica, il dissesto idrogeologico, la crisi economica e ambientale. La terza parte del volume enuncia, infine, una serie di prospettive di lavoro coerenti con le questioni sollevate. Strategie urbanistiche, paesaggistiche, fiscali e sociali, che tracciano i lineamenti di un possibile programma di riforma in cui il rigore nel perseguimento dell’interesse pubblico sappia stare assieme alla piena consapevolezza del difficile contesto in cui si opera

G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling