IRIS UniSR (’Università Vita-Salute San Raffaele)
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Breastfeeding after breast cancer in young BRCA carriers
No full textBackground We investigated safety of breastfeeding after breast cancer in patients carrying germline BRCA pathogenic or likely pathogenic variants.Methods This was an international, multicenter, hospital-based, retrospective cohort study including BRCA carriers diagnosed with stage I-III invasive breast cancer at age 40 years or younger between January 2000 and December 2020 (NCT03673306). Locoregional recurrences and/or contralateral breast cancers, disease-free survival (DFS), and overall survival (OS) were compared between patients who breastfed after delivery and those who did not.Results Among 4732 patients included from 78 centers worldwide, 659 had a pregnancy after breast cancer diagnosis, of whom 474 delivered a child. After excluding patients with uptake of bilateral risk-reducing mastectomy prior to delivery (n = 225) or unknown breastfeeding status (n = 71), 110 (61.8%) breastfed (median duration 5 months) and 68 (38.2%) did not breastfeed. Compared to patients in the no breastfeeding group, those who breastfed were more frequently nulliparous at breast cancer diagnosis (61.8% vs 45.6%) and did not report prior smoking habit (71.8% vs 57.4%). After a median follow-up of 7.0 years following delivery, 7-year cumulative incidence of locoregional recurrences and/or contralateral breast cancers was 29% in the breastfeeding group and 36% in the no breastfeeding group (adjusted subdistribution hazard ratio [HR] = 1.08, 95% CI = 0.57 to 2.06). No difference in DFS (adjusted hazard ratio [aHR] = 0.83, 95% CI = 0.49 to 1.41) nor in OS (aHR = 1.32, 95% CI = 0.31 to 5.66) was observed.Conclusions Breastfeeding did not appear to be associated with a higher risk of developing locoregional recurrences or contralateral breast cancers, emphasizing the possibility of achieving a balance between maternal and infant needs without compromising oncological safety
«Sinché la perfetta arte non diventi di nuovo natura». Progresso e regresso morale in Kant
No full textKant struggles with the problem of moral regress throughout all his philosophy of history. The solution he finally argues for in The Contest of Faculties (1798) is the result of a complex elaboration in which the practical-empirical issue of regress is explained in the light of the theoretical justification of progress developed in the Critique of the Power of Judgment (1790). The article argues that this solution is consistent
Insights into the European heart failure epidemiology
No full textAims: The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), together with the National Heart Failure Societies (NHFS), designed the European Heart Failure (HF) Survey with an aim of assessing contemporary HF epidemiology, management resources, availability and reimbursement of guideline-directed medications and devices, and structure of professional and patient organizations. This document presents data on HF epidemiology. Methods and results: The European HF Survey was conducted in 43 ESC member countries. Epidemiology data were exclusively collected from national health statistics from 2019, and standardized according to the European Standard Population, with variable response rates and data completeness among the countries. Median annual HF incidence was 3.9 patients per 1000 person-years (interquartile range [IQR] 3.1–6.5), and median HF prevalence was 1937 patients (IQR 1463–3416) per 100 000 population. Median in-hospital mortality of patients admitted for HF was 8.0% (IQR 4.9–9.6%), and median 1-year all-cause mortality of patients with HF was 14.5% (IQR 8.2–21.6%). Median number of HF-related hospitalizations was 333 (IQR 230–469) per 100 000 population, and median length of stay for HF-related hospitalizations was 8.5 (IQR 7.2–9.2) days. A heterogeneity in HF epidemiology statistics was observed across different countries. Conclusions: The European HF Survey provides a contemporary insight into HF epidemiology and outcomes across the ESC member countries. These data are valuable to inform strategies to improve prevention, diagnosis, and management of HF. The persisting gaps and considerable heterogeneity in epidemiology statistics highlight the need to further unify data collection and reporting practices across European countries
Clinical Management of Gingival Recessions with or Without Cervical Lesions: A Decisional Scheme Proposal
No full textBackground: Treatment of gingival recessions starts from an accurate diagnosis considering both periodontal tissue status and adjacent exposed dental tissues. Based on current scientific evidence and the authors’ clinical experience, a decisional scheme has been proposed for the management of gingival recession defects, with or without non-carious cervical lesions, taking into account gingival thickness and interproximal attachment levels. To illustrate its practical application, a series of representative clinical cases is presented, documenting the rationale and outcomes of the therapeutic decisions. Methods: According to the 2017 World Workshop Classification of Periodontal and Peri-Implant Diseases and Conditions, the gingival recession defect classifications have been used to build up a decision-making therapeutic process. Combined periodontal and restorative treatments in presence or absence of dental lesions have been performed. Results: In case of an identifiable cemento-enamel junction (CEJ) with or without non-carious cervical lesions (class A+ and class A−, respectively) and absence of interproximal attachment loss (RT1), flap approaches alone or in combination with connective tissue graft (CTG) were suggested. In case of an unidentifiable CEJ without cervical lesion (class B−), flap approaches alone were proposed in presence of adequate residual keratinized tissue (KT) and absence of interproximal attachment loss (RT1); if KT is extremely reduced, flap approaches + CTG may be performed. If the unidentifiable CEJ is associated with cervical lesions involving both root and crown surfaces (class B+), the combined restorative–periodontal treatment results as the most indicated approach. The adjunctive use of CTG should be also considered in presence of interproximal attachment loss (RT2 and RT3) and reduced gingival thickness (<1 mm). Conclusions: The proposed decisional scheme could be useful to address the clinicians during the decision-making process in the treatment of gingival recessions
Prevalence and Determinants of Workplace Violence Against Nurses in the Italian Home Care Settings: A Cross-Sectional Multicentre Study
No full textAims: To describe the prevalence and determinants of workplace violence against nurses in the Italian home care setting. Design: Secondary cross-sectional analysis of data from the multicentre study AIDOMUS-IT. Methods: Nurses employed in home care services provided by Italian Local Health Authorities were interviewed using a variety of instruments. A multivariable binary logistic regression model was performed to model the risk of workplace violence against nurses in the last 12 months. Variables related to violence were selected among sociodemographic characteristics (such as age and gender), work-related factors (including years of experience, team composition, overtime working, previous experience in mental health care, burnout) and organisational elements (including leadership and support, workload, staffing and resources adequacy, and time to reach the patients' homes). Adjusted odds ratios (aOR) were used to present the results. Results: A total of 3949 nurses participated in the study and 20.49% of them reported to have experienced an episode of violence in the last 12 months. Determinants of higher risk of violence episodes were younger age (aOR = 1.02, p = 0.002), higher workload (aOR = 1.01, p = 0.002), working in a multiprofessional team (aOR = 1.24, p = 0.018), perception of inadequate managerial leadership and support (aOR = 1.38, p = 0.003), and higher burnout levels (aOR = 1.01, p < 0.001). Conclusion: The prevalence of workplace violence against Italian home care nurses is high. Several modifiable determinants were found to be associated with a higher risk of violence, which can potentially be mitigated with tailored interventions. Implications for the Profession and/or Patient Care: Effective preventive strategies must be developed to lessen workplace violence against nurses in the home care setting. These strategies should focus on strengthening nursing managers' leadership and support skills, enhancing team-building strategies, avoiding inadequate workload, monitoring nurses' burnout, estimating optimum staffing levels, and assigning advanced-career nurses to home care services. These measures are imperative to guarantee the quality and safety of home care organisations and to attain favourable outcomes in the provision of care. Impact: This study aimed to explore the prevalence and determinants of workplace violence against nurses in the Italian home care settings. We found that out of the 3949 nurses surveyed, 20% of the sample reported one episode of violence during the last 12 months. Determinants of this violence included younger age, higher workload and burnout, being in a multiprofessional team, and perception of lack of leadership and support by the nurse manager. The results of this study can be used to tailor interventions aimed at mitigating the risk factors of violence, particularly those that can be modified (e.g., workload, burnout, and leadership). Reporting Method: The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Patient or Public Contribution: No patient or public contribution
Experimental Design
No full textThe aim of this chapter is to describe issues related to the choice of an optimal design for fMRI experiments. More specifically, it describes how the psychological process of interest is isolated and contrasted using fMRI, and how principal fMRI designs divide into block, event-related, and participant-response dependent designs. The topic of data analysis, with particular emphasis on optimizing and isolating the signal in activated brain regions, is illustrated. Finally, a number of practical matters related to study design are addressed, including optimal sample sizes and trial durations
Altered calcium responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes
No full text: Friedreich's ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. While several studies highlight cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy. We treated primary cerebellar astrocytes with an RNA interference-based approach, to achieve a reduction of FXN comparable to that observed in patients. These FRDA-like astrocytes display some typical features of the disease, such as an increase of oxidative stress and a depletion of glutathione content. Moreover, FRDA-like astrocytes exhibit decreased calcium responses to purinergic stimuli. Our findings shed light on cellular changes caused by FXN downregulation in cerebellar astrocytes, likely impairing their complex interaction with neurons. The potentially impaired ability to provide neuronal cells with glutathione or to release neuromodulators in a calcium-dependent manner could affect neuronal function, contributing to neurodegeneration.Friedreich’s ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. Although several studies have highlighted cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy. We treated primary cerebellar astrocytes with an RNA interference-based approach, to achieve a reduction of FXN comparable to that observed in individuals with FRDA. These FRDA-like astrocytes display some typical features of the disease, such as an increase of oxidative stress and a depletion of glutathione content. Moreover, FRDA-like astrocytes exhibit decreased Ca2+ responses to purinergic stimuli. Our findings shed light on cellular changes caused by FXN downregulation in cerebellar astrocytes, likely impairing their complex interaction with neurons. The potentially impaired ability to provide neuronal cells with glutathione or to release neuromodulators in a Ca2+-dependent manner could affect neuronal function, contributing to neurodegeneration
Clinical perspective: Advancing hemophilia treatment through gene therapy approaches
No full textHemophilia, a congenital bleeding disorder, can cause arthropathy, impaired mobility, pain, and life-threatening hemorrhage events, significantly impacting quality of life for patients and caregivers. Current therapies, although effective, necessitate costly lifelong treatment, often in specialized settings. However, as a monogenic disorder caused by loss-of-function genetic variants, hemophilia is amenable to gene therapy. In this article, three primary gene therapy approaches at the forefront of clinical development are reviewed. Adeno-associated virus-based gene therapy, having secured approval in the EU, UK, and US after promising phase 3 trial results, demonstrates clear superiority over standard-of-care treatment. Lentivirus-based approaches capable of transducing dividing and nondividing cells may improve the durability of treatment and have low susceptibility to pre-existing neutralizing antibodies to viral vectors. Finally, gene editing techniques such as zinc finger nucleases and CRISPR aim to correct genetic defects directly, holding promise as novel, effective, and highly durable therapeutic strategies in adults and children with hemophilia. This review provides a comprehensive summary of the current status of these gene therapy approaches, highlighting advantages, limitations, and potential future developments
Empowering women at the heart of autosomal dominant polycystic kidney disease: Addressing unique challenges gender-sensitive approach
Full text linkAutosomal dominant polycystic kidney disease is a genetic disorder characterized by the progressive development of renal cysts, leading to end-stage renal disease in a significant proportion of affected individuals. While the disease affects both men and women, emerging evidence suggests that sex differences may influence the clinical presentation, progression, and response to treatment in autosomal dominant polycystic kidney disease patients. Based on our experience, women are diagnosed earlier and often experience more symptoms like chronic pain and microhematuria. However, disease progression tends to be slower. Hormonal therapy, controversial due to its impact on cyst growth, is important for contraception and conditions like polycystic ovary syndrome, endometriosis, and menopause. Copper intrauterine devices are the safest contraceptive option, while progestin-only methods are recommended for those who cannot take estrogen. This review aims to explore the implications of gender differences in autosomal dominant polycystic kidney disease, highlighting the need for personalized approaches to diagnosis, monitoring, and management. Emphasizing the integration of gender-based insights into clinical practice could ultimately lead to more tailored therapeutic strategies, improving patient outcomes in autosomal dominant polycystic kidney disease