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[Treatment of heart failure with sodium-glucose cotransporter 2 inhibitors across the spectrum of left ventricular function]
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Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration
No full textImportance: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration. Objective: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration. Design, setting, and participants: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023. Inclusion criteria were asymptomatic ATTR cardiac amyloid infiltration, defined as an absence of HF history, HF signs and symptoms, diuretic therapy, and plasma cell dyscrasia with evidence of myocardial uptake on bone scintigraphy. If plasma cell dyscrasia was present, histologic confirmation of ATTR amyloid was required. Exposure: Asymptomatic ATTR cardiac amyloid infiltration. Main outcomes and measures: The primary outcomes were all-cause and cardiovascular (CV) mortality. The secondary outcomes were unplanned HF hospitalization, unplanned CV-related hospitalization, and a composite outcome of CV mortality and HF hospitalization. Results: The study comprised 485 patients with asymptomatic ATTR cardiac amyloid infiltration (mean [SD] age, 74.9 [9.9] years, 85.8% male, 112 [23.1%] with hereditary ATTR amyloidosis), with 369 (76.1%) having grade 2 or 3 and 116 (23.9%) having grade 1 cardiac uptake at baseline. Patients with grade 2 or 3 uptake exhibited significantly more cardiac functional and structural abnormalities vs patients with grade 1 uptake. At 3 years, compared with grade 1 uptake, patients with grade 2 or 3 uptake had greater development of HF (54.3% [95% CI, 47.7%-61.3%] vs 23.1% [95% CI, 14.8%-35.1%]), greater outpatient diuretic initiation and N-terminal pro-B-type natriuretic peptide progression (35.0% [95% CI, 28.0%-43.2%] vs 12.4% [95% CI, 6.3%-23.7%]), and greater HF hospitalization (8.7% [95% CI, 5.9%-12.9%] vs 0%) and unplanned CV hospitalization (20.0% [95% CI, 15.7%-25.3%] vs 4.3% [95% CI, 1.6%-11.3%]). Over a median follow-up of 37 months (IQR, 20-64 months), the all-cause death rate was similar between patients with grade 1 vs 2 and 3 uptake; however, those with grade 2 or 3 compared with grade 1 uptake had a significantly higher risk of CV mortality (unadjusted hazard ratio, 5.30; 95% CI, 1.92-14.65). Conclusions and relevance: This study shows that asymptomatic ATTR cardiac amyloid infiltration encompasses a wide spectrum of disease severity, with patients with grade 2 or 3 cardiac uptake experiencing an increased rate of CV events and CV mortality and patients with grade 1 uptake experiencing a lower CV event rate and predominantly non-CV mortality. These findings support the use of disease-modifying treatments in asymptomatic patients with grade 2 or 3 uptake and highlight the need of large-scale studies to assess their role in grade 1 uptake
Optimizing Attended Home Delivery: Multiple recovery options and customer availability profiles to face synchronization failures
Get PDFIn the growing sector of Attended Home Delivery, unsynchronized deliveries between couriers and recipients affect both customers’ satisfaction and companies’ costs. Hence, reducing such failures improves companies’ service quality and logistics efficiency. To address this issue, we study an Attended Home Delivery Problem with Recovery Options (AHDPRO) in which customers specify their probability of being at home during different timeslots of the day and their preferred recovery option in case of a synchronization failure. The options include leaving the package in a predefined safe location, bringing it to a generic collection point, or scheduling a second delivery attempt. Each alternative involves different costs and, in most cases, additional operational decisions. The AHDPRO aims to complete all customer deliveries while minimizing overall routing times as well as the overall penalty due to the recovery actions implemented and weighted by the probability of a synchronization failure to occur. We propose a branch-and-cut algorithm, including valid inequalities and heuristic procedures, to solve a Mixed-Integer Linear Programming model based on an expanded graph. Using the developed method as a tool for evaluating costs and operations, we conduct an experimental campaign on scenarios adapted from the literature involving lexicographic-based optimization procedures able to address the multiple attributes of the solutions. The results obtained allow us to assess the impact of the different recovery options on the optimal solutions and their values. Additionally, the results yield several managerial insights for companies operating in the Attended Home Delivery sector, such as the timeslot length, perceived service quality, and other key operational factors contributing to efficient planning and improved customer satisfaction
Prognostic Role of Pretreatment Tumor Burden and Dissemination Features From 2‐[18F]FDG PET/CT in Advanced Mantle Cell Lymphoma
No full text: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with poor prognosis. The usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) and its parameters in the evaluation of treatment response and prognosis is not yet clear. The aim of this study was to investigate the prognostic role of tumor burden and tumor dissemination features derived by 2-[18F]FDG PET/CT in advanced MCL. We retrospectively included 120 patients with advanced MCL who underwent baseline 2- 2-[18F]FDG PET/CT and end-of-treatment (eot) PET/CT. The baseline-PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and dissemination features (Dmax and Dmax-bsa). EotPET/CT was judged according to the Lugano classification. Progression-free survival (PFS) and overall survival (OS) were plotted according to the Kaplan-Meier method. At a median follow-up of 59 months, relapse/progression occurred in 68 patients while death in 38 patients with a median PFS and OS of 27.2 and 57.6 months, respectively. MIPI score, Bulky disease, Ki-67 index, metabolic response, pretreatment MTV and TLG were significantly associated with PFS at univariate analysis, but only metabolic response, MTV and TLG were confirmed to be independent prognostic factors. Considering OS, only dissemination features were demonstrated to be prognostic features. In conclusions, metabolic response and metabolic tumor burden parameters (MTV and TLG) are strongest predictor of PFS, while dissemination features may have a significant role for predicting OS
The role of the frailty in the evaluation of injury risk factors for National Basketball Association players
Get PDFInjuries often occur in sports and, due to medical and economic reasons, it is important to understand the factors that mainly affect the risk of experiencing them. This work aims to explore this field in the context of the National Basketball Association (NBA) league. Thus, the main purpose is to identify the main individual players' characteristics that are associated to a higher risk of suffering an injury in a shorter time, taking into account ten seasons, from the beginning of 2010-2011 season until the end of 2019-2020 season. All the needed information has been retrieved from different big datasets regarding NBA players. The work stands in the survival data analysis framework and, for the purpose, a Cox regression model with frailty has been used. Results suggest that the player's position and the Body Mass Index have a significant effect on the injury's risk. From a methodological point of view, this manuscript provides an insight into the role of the frailty in the model, studying its relationship with the residuals of a mispecified Cox model
Challenging the Binary Classification of Endometrioid Endometrial Adenocarcinoma: The Evaluation of Grade 2 as an Independent Entity Based on Prognostic Characteristics and Recurrence Patterns
Get PDFBackground: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate the outcomes, prognostic factors and recurrence patterns of G2 EEC and whether the differentiation between G1 and G2 EEC is clinically useful. Methods: we retrospectively reviewed 523 patients with EEC treated with primary surgery over a decade (March 2010-January 2020) at Oxford University Hospitals NHS Trust, focusing on those with G2 disease. Results: Patients with G2 EEC had worse 5-year cancer-specific survival (93.3% vs. 98.5%, p < 0.01) compared to patients with G1 EEC, but a favourable prognosis compared to G3 EEG, both in terms of disease-free survival (91.6 vs. 83.8%, p = 0.04) and cancer-specific survival (93.3% vs. 78.5%, p < 0.01). Both stage and grade are independent risk factors for cancer-specific mortality in EEC. Cervical stromal involvement, parametrial involvement and distant metastatic disease are all independent risk factors for cancer-related mortality in G2 ECC. Only 12.5% of recurrences of G2 EEC were diagnosed with examination in routine follow up in asymptomatic patients. Conclusions: our results suggest that the grading system should continue to differentiate G1 EEC and G2 EEC for better prognosis interpretation
The debate on the origin of springs in Italy in the age of the Scientific Revolution
No full textIn the second half of the 17th century, Perrault's and Mariotte's works, followed by Halley's measures of evaporation, paved the way to the comprehenison of the hydrological cycle as it is currently understood. In Italy the debate was lively and involved a number of scholars, who actively or only cursorily dealt with the theme. They were pure or applied mathematicians, natural scientists, Jesuit scholars and physicians, technicians and connoisseurs of the matter. In this work we reanalyse this complex and multifaceted debate, which, over the course of the century from 1642 to 1741, slowly came to the acceptance of the new paradigm, in the light of the following interpretative keys: (i) the relationship with the coeval international literature, (ii) the legacy of Galilean and Newtonian mechanics, (iii) the attitude towards measurement and experimental practice, (iv) the persistencies of the Aristotelian epistemology and perception of Nature
