University of Milan

About: University of Milan is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Transplantation. The organization has 58413 authors who have published 139784 publications receiving 4636354 citations. The organization is also known as: Università degli Studi di Milano & Statale.

Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23–01): a phase 3 randomised controlled trial

Abstract: Summary Background For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23–01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. Methods In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. Findings Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6–7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4–91·2) in the group without axillary dissection and 84·4% (80·7–88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55–1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3–4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. Interpretation Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. Funding None.

Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

Abstract: Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7–29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential.

Prognostic Value of Ambulatory and Home Blood Pressures Compared With Office Blood Pressure in the General Population Follow-Up Results From the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) Study

Abstract: Background— Studies in hypertensive patients suggest that ambulatory blood pressure (BP) is prognostically superior to office BP. Much less information is available in the general population, however. Obtaining this information was the purpose of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Methods and Results— Office, home, and 24-hour ambulatory BP values were obtained in 2051 subjects between 25 and 74 years of age who were representative of the general population of Monza (Milan, Italy). Subjects were followed up for an average of 131 months, during which time cardiovascular and noncardiovascular fatal events were recorded (n=186). Office, home, and ambulatory BP values showed a significant exponential direct relationship with risk of cardiovascular or all-cause death. The goodness of fit of the relationship was greater for systolic than for diastolic BP and for night than for day BP, but its overall value was not better for home or ambulatory than for office BP. The slope of...

The Assembly and Merging History of Supermassive Black Holes in Hierarchical Models of Galaxy Formation

Abstract: We assess models for the assembly of supermassive black holes (SMBHs) at the center of galaxies that trace their hierarchical buildup far up in the dark halo merger tree. Motivated by the recent discovery of luminous quasars around redshift z ≈ 6—suggesting a very early assembly epoch—and by numerical simulations of the fragmentation of primordial molecular clouds in cold dark matter (CDM) cosmogonies, we assume that the first seed black holes (BHs) had intermediate masses and formed in (mini)halos collapsing at z ~ 20 from high-σ density fluctuations. As these pregalactic holes become incorporated through a series of mergers into larger and larger halos, they sink to the center because of dynamical friction, accrete a fraction of the gas in the merger remnant to become supermassive, form a binary system, and eventually coalesce. The merger history of dark matter halos and associated BHs is followed by cosmological Monte Carlo realizations of the merger hierarchy from early times until the present in a ΛCDM cosmology. A simple model, where quasar activity is driven by major mergers and SMBHs accrete at the Eddington rate a mass that scales with the fifth power of the circular velocity of the host halo, is shown to reproduce the observed luminosity function of optically selected quasars in the redshift range 1 < z < 5. A scheme for describing the hardening of a BH binary in a stellar background with core formation due to mass ejection is applied, where the stellar cusp proportional to r-2 is promptly regenerated after every major merger event, replenishing the mass displaced by the binary. Triple BH interactions will inevitably take place at early times if the formation route for the assembly of SMBHs goes back to the very first generation of stars, and we follow them in our merger tree. The assumptions underlying our scenario lead to the prediction of a population of massive BHs wandering in galaxy halos and the intergalactic medium at the present epoch and contributing 10% to the total BH mass density, ρSMBH = 4 × 105 M☉ Mpc-3 (h = 0.7). The fraction of binary SMBHs in galaxy nuclei is on the order of 10% today, and it increases with redshift so that almost all massive nuclear BHs at early epochs are in binary systems. The fraction of binary quasars (both members brighter than 0.1L*) instead is less than 0.3% at all epochs. The nuclear SMBH occupation fraction is unity (0.6) at the present epoch if the first seed BHs were as numerous as the 3.5 σ (4 σ) density peaks at z = 20.