Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Nipple-Sparing Mastectomy After Neoadjuvant Chemotherapy: Definitive Results with a Long-Term Follow-Up Evaluation

Background. Nipple-sparing mastectomy (NSM) is increasingly used for women with breast cancer who are not candidates for conservative surgery. The authors previously reported satisfying results with NSM after neoadjuvant chemotherapy (NACT). Methods. From 2010 to 2020, 1072 women underwent mastectomy at the authors' institution. In this group, 433 NSMs were performed (40%). The only contraindications to NSM were close proximity to the nipple-areola complex (NAC), bloody discharge, and Paget disease. Results. In 112 cases involving 111 women, NSM followed NACT (group 1), whereas it was performed as primary surgery in 321 instances involving 306 women (group 2). At 5 years, local relapse was 7% in group 1 and 2% in group 2, although in the multivariate analysis, locoregional relapses (LRRs) did not differ between the two groups. An increased incidence of local relapse was associated with higher tumor stage (stage III; p = 0.046) and age younger than 51 years (p = 0.038). For 34 (30.3%) of the 111 women in group 1 with a pathologic complete response (pCR), no LRRs were recorded. Only one NAC recurrence was observed. Overall survival with each tumor stage did not differ between the two groups. No differences in complications were observed. Cosmetic results were satisfying in 83.8% of the cases and did not get worse after NACT. Conclusions. The study data definitively confirm that NSM is safe even after NACT, with good cosmetic results and complications comparable with those in the primary surgery setting. Tumor stage and age were the only independent factors for local relapse. Patients with pCR enjoyed optimal locoregional control

Long-term outcomes of once-daily accelerated partial-breast irradiation with tomotherapy: results of a phase 2 trial

Purpose: We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after breast conservative surgery. Methods and materials: From December 2010 to December 2018, we treated 338 women with APBI-tomotherapy: 38.5 Gy in 10 once-daily fractions. Patients selected were age ≥50 years old, with ≤3 cm in size unifocal tumor and at least 2 mm of clear margins. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes, and American Society for Radiation Oncology (ASTRO) 2017 updated consensus groupings. Results: The median age was 65 years (range, 50-86). The invasive ductal (87.5%) and the luminal A-like molecular phenotype (70%) were the most common tumors. Overall 242 patients (71.6%) were considered "suitable" for enrollment in APBI according to the eligibility criteria of the ASTRO-2017 consensus statement. With a median follow-up of 76 months (range, 17-113), 2 patients (0.6%) had an invasive ipsilateral breast tumor recurrence (IBTR), and 2 patients (0.6%) had an axillary ipsilateral failure. The rate of local control in terms of free of IBTR was 99.4% and locoregional control (no recurrence in ipsilateral breast as well as in regional nodes) was 98.8%. Progression-free survival was 98.4% and 92% at 5 and 10 years, respectively. Acute and late skin toxicity, graded according to the Common Terminology Criteria for Adverse Events, were 7.7% (G1) and 0.6% (G2) and 4.4% (G1) and 1.1% (G2), respectively. There were no grade 3/4 toxicities, however. Very few patients (2%) or physicians (2%) assessed cosmetic outcome as fair or poor at the 2-year follow-up. Conclusions: This phase 2 trial on APBI-tomotherapy shows excellent long-term results. Once-daily fractionation schedule was well tolerated with a low rate of adverse events and worse cosmetic outcome. In this series, even among those deemed cautionary or unsuitable for APBI by ASTRO criteria, we demonstrated a low rate of IBTR

Long-Term Effectiveness of Liraglutide for Treatment of Type 2 Diabetes in a Real-Life Setting: A 24-Month, Multicenter, Non-interventional, Retrospective Study

<h2>Article full text</h2><p>The full text of this article can be found here <a href="https://link.springer.com/article/10.1007/s12325-017-0652-2">https://link.springer.com/article/10.1007/s12325-017-0652-2</a>.</p><h2>Provide enhanced content for this article</h2><p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”">[email protected]</a>.</p><p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p><p>Other enhanced features include, but are not limited to:</p><ul><li>Slide decks</li><li>Videos and animations</li><li>Audio abstracts</li><li>Audio slides</li></ul

1. Seminario Nazionale di Biblioteconomia

DIDATTICA E RICERCA NELL’UNIVERSITA ITALIANA E CONFRONTI INTERNAZIONALI Il volume raccoglie la maggior parte dei contributi che sono stati presentati e discussi il 30 e 31 maggio 2013, nel corso del primo “Seminario nazionale di biblioteconomia” organizzato, nell’ambito delle attività scientifiche del Dipartimento di Scienze documentarie, linguistico-filologiche e geografiche dell’Università di Roma La Sapienza, da Alberto Petrucciani e Giovanni Solimine, con il patrocinio della Facoltà di Lettere, dell’Associazione italiana biblioteche (AIB) e della Società italiana di scienze bibliografiche e biblioteconomiche (SISBB)

From pediatric to adult care: a survey on the transition process in type 1 diabetes mellitus and the diabetes services in Italy

AimsThe present study assessed the transitioning process of young adults with type 1 diabetes mellitus (T1D) in Italy.Materials and methodsWe asked Pediatric Diabetes Centers (PDC) and Adult Diabetes Centers (CAD) to fill in a web-based survey on the current state of services, the number of transitioning adolescents with T1D within the last year, observations on limitations, and future directions.Results93 centers (46 PDCs, 47 CADs) joined the study. The total number of subjects with T1D being followed by a PDC was 16,261 (13,779 minors and 2483 young adults), while CADs had 25,500 patients. The survey showed an uneven situation. Only some services had a dedicated diabetes team (78% of PDCs, 64% of CADs). 72% of PDCs and 58% of CADs reported a protocol dedicated to transition. The median age for transition was 19 (range 16-25 years); the time required for preparing transition, indicated by both PDCs and CADs, was 5.5 months. A high percentage of CADs (80%) confirmed receiving sufficient clinical information, mainly through paper or computerized reports. The transition process is hampered by a lack of resources, logistical facilities, and communication between services. While some services have a protocol, monitoring of results is only carried out in a few cases. Most specialists expressed the need to enhance integration and continuity of treatment.ConclusionsThe current situation could be improved. Applying standard guidelines, taking into consideration both clinicians' and patients' necessities, would lead to a more successful transition process

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk