IRIS UniSR (’Università Vita-Salute San Raffaele)
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When Silence Breaks: The Influence of Pure Tones and White Noises on Conditioned Flight Responses
Full text linkBackground: The flight response is part of the repertoire of adaptive behavioral responses all animals possess and use to face threats coming from their environment. Compared to the other responses, flight requires a high degree of physical effort and is thought to be related to those active coping strategies that can be observed in several psychopathological conditions, including anxiety and depressive disorders. In recent years, a new protocol of auditory fear conditioning has been shown to induce a learned flight response in mice, based on a conditioned stimulus that includes pure tones and white noise, the serial compound stimulus (SCS). Methods: In this review, we examine the effects of stimulus characteristics in fear learning paradigms, particularly in the context of the recently developed SCS paradigm. We will discuss how factors such as conditioned stimulus (CS) modality (e.g., tone versus white noise), stimulus salience, and the temporal relationship between stimuli influence conditioned flight responses. Results: For the study of both physiological and maladaptive behaviors, fear conditioning still represents the paradigm of choice, e.g., for the modeling of psychiatric conditions such as post-traumatic stress disorder or phobias. Albeit its relevance in this context, up to now only a few studies have focused on developing procedures for eliciting conditioned flight responses in the laboratory, in favor of freezing/immobilization, the so-called fright response. The SCS protocol poses new interesting questions on the impact of noises and other stimuli on learning and behavioral responses. Conclusion: The discovery of SCS already led to interesting findings in the neurobiology of fear learning and shows great potential for the study of maladaptive responses in animal models of psychopathology
Keratoconus: The Local Manifestation of a Systemic Disease?
No full textKeratoconus (KC) is the most common ectatic corneal disease. In this review, the systemic aspects of the disease are discussed, including patient age, genetics, systemic inflammatory status and immune system dysregulation, atopy and eye rubbing, systemic metabolism, the metabolism of micronutrients (including vitamin D), and hormonal balance. The association between KC and metabolic diseases, collagen diseases, and psychiatric conditions is also considered. The evidence that is currently available strongly suggests a systemic predisposition toward KC. The understanding that KC may be the local manifestation of a systemic disease could allow earlier detection/prevention and pave the way for research into new treatments addressing the pathogenetic foundations of KC, rather than limiting intervention to the corneal disease
Knowledge and application of ESC/HFA guidelines in the management of advanced heart failure
No full textAims Management of advanced heart failure (HF) remains challenging despite specific sections in the 2021 European Society of Cardiology/Heart Failure Association (ESC/HFA) guidelines, with delays in referrals exacerbating the issue. This study aimed to evaluate the awareness and implementation of these guidelines among cardiologists and identify barriers to effective referral. Methods and results From June to October 2023, an online survey was disseminated through the ESC mailing list, targeting cardiologists across Europe. The survey investigated four areas: guideline awareness, healthcare network organization, clinical case management, and perceptions of mechanical circulatory support (MCS) outcomes. Respondents were categorized into heart failure cardiologists (HFCs), general cardiologists (GCs), and other participants (OPs). Among 497 respondents, 25% were heart HFCs, 40% were GCs, and 35% were OPs. A total of 84% of HFCs reported a high level of guideline knowledge, compared to 57% of GCs and 62% of OPs (p < 0.001). Additionally, 76% of HFCs 'regularly or always' used ESC/HFA criteria to identify advanced HF, compared to 44% of GCs and 48% of OPs (p < 0.001). Correct responses regarding the recommendation class for heart transplantation were 84%, 55%, and 60% (p < 0.0001), and for MCS as a bridge to transplantation, 69%, 65%, and 55% (p = 0.018) among HFCs, GCs, and OPs, respectively. Referring patients with severe HF to a tertiary centre team was found to be 'very difficult' or 'difficult' by 8.4% of HFCs, 19.6% of GCs, and 18.2% of OPs (p = 0.0005). Conclusion The study highlights significant disparities in knowledge and application of advanced HF guidelines among cardiologists, revealing an opportunity for educational initiatives. The difficulty in referring patients to tertiary centres underscores the need to improve the referral pathway for advanced HF patients.Aims: Management of advanced heart failure (HF) remains challenging despite specific sections in the 2021 European Society of Cardiology/Heart Failure Association (ESC/HFA) guidelines, with delays in referrals exacerbating the issue. This study aimed to evaluate the awareness and implementation of these guidelines among cardiologists and identify barriers to effective referral. Methods and results: From June to October 2023, an online survey was disseminated through the ESC mailing list, targeting cardiologists across Europe. The survey investigated four areas: guideline awareness, healthcare network organization, clinical case management, and perceptions of mechanical circulatory support (MCS) outcomes. Respondents were categorized into heart failure cardiologists (HFCs), general cardiologists (GCs), and other participants (OPs). Among 497 respondents, 25% were heart HFCs, 40% were GCs, and 35% were OPs. A total of 84% of HFCs reported a high level of guideline knowledge, compared to 57% of GCs and 62% of OPs (p < 0.001). Additionally, 76% of HFCs ‘regularly or always’ used ESC/HFA criteria to identify advanced HF, compared to 44% of GCs and 48% of OPs (p < 0.001). Correct responses regarding the recommendation class for heart transplantation were 84%, 55%, and 60% (p < 0.0001), and for MCS as a bridge to transplantation, 69%, 65%, and 55% (p = 0.018) among HFCs, GCs, and OPs, respectively. Referring patients with severe HF to a tertiary centre team was found to be ‘very difficult’ or ‘difficult’ by 8.4% of HFCs, 19.6% of GCs, and 18.2% of OPs (p = 0.0005). Conclusion: The study highlights significant disparities in knowledge and application of advanced HF guidelines among cardiologists, revealing an opportunity for educational initiatives. The difficulty in referring patients to tertiary centres underscores the need to improve the referral pathway for advanced HF patients
Rectal Cancer Segmentation: A Methodical Approach for Generalizable Deep Learning in a Multi-Center Setting
No full textNoninvasive Artificial Intelligence (AI) techniques have shown great potential in assisting clinicians through the analysis of medical images. However, significant challenges remain in integrating these systems into clinical practice due to the variability of medical data across multi-center databases and the lack of clear implementation guidelines. These issues hinder the ability to achieve robust, reproducible, and statistically significant results. This study thoroughly analyzes several decision-making steps involved in managing a multi-center database and developing AI-based segmentation models, using rectal cancer as a case study. A dataset of 1212 Magnetic Resonance Images (MRIs) from 14 centers was used. The study examined the impact of different image normalization techniques, network hyperparameters, and training set compositions (in terms of size and construction strategies). The findings emphasize the critical role of image normalization in reducing variability and improving performance. Additionally, the study underscores the importance of carefully selecting network structures and loss functions based on the desired outcomes. The potential of clustering approaches to identify representative training subsets, even with limited data sizes, was also evaluated. While no definitive preprocessing pipeline was identified, several networks developed during the study produced promising results on the external validation set. The insights and methodologies presented may help raise awareness and promote more informed decisions when implementing AI systems in medical imaging
Exploring Social Support in Ostomy Patients: A Scoping Review
No full textStrong social support plays a crucial role in shaping the overall quality of life for ostomy patients. However, no comprehensive review has yet explored the role of social support for both ostomy patients and their informal caregivers. This study aims to map the existing literature on social support for ostomy patients and their caregivers. We conducted a scoping review following the guidelines provided in the Joanna Briggs Institute Manual for Evidence Synthesis. A three-step search strategy was implemented across several databases, including MEDLINE via PubMed, CINAHL and Scopus. The review included 23 articles. However, none of the included studies specifically addressed the role of social support for informal caregivers. The social networks of ostomy patients typically include family members, friends, support groups and other significant individuals. There is still little literature examining the effect of social support in adolescents with ostomies. Our findings revealed considerable heterogeneity in the tools used to measure social support. Most of the research focussed on the relationship between social support and quality of life, with few studies investigating its impact on patients' self-care, mental health or clinical outcomes. This review serves as a foundation for future studies on the subject. Further research is needed to explore social support from the perspectives of both ostomy patients and their informal caregivers
Correction: Creation of Side-to-Side Compression Anastomosis Using the GT Metabolic SolutionsTM Magnet System, DI Biofragmentable (MagDITM System) to Achieve Duodeno-Ileal Diversion in Patients with Obesity: Preliminary Italian Multi-Center Results (Obesity Surgery, (2025), 10.1007/s11695-025-08409-z)
No full textIn the published article there is an error in the name of the fourth author. The correct name is Giovanni Cesana
Connected Speech Alterations and Progression in Patients With Primary Progressive Aphasia Variants
Full text linkBackground and Objectives Diagnosing the different variants of primary progressive aphasia (PPA) is challenging, but more accurate characterization can improve patient management and treatment outcomes. This study aimed to identify the following: (1) which speech features, alone or combined with language assessment and gray matter volumes (GMVs), best distinguish PPA variants and (2) how connected speech evolves in PPA. Methods This prospective study was conducted at IRCCS San Raffaele Hospital in Milan, Italy, between 2010 and 2021. We included patients with PPA who underwent neuropsychological assessments, including standard evaluation of language and the “Picnic Scene” speech test, and, when available, brain structural MRI. Clinical and language assessments were also performed at follow-up in a subgroup. Sequential feature selection models identified speech parameters that best differentiated groups, incorporating age, sex, education, standard language tests, and GMVs. In each PPA group, linear mixed-effect models analyzed speech changes over time. Results We included 95 patients with PPA (mean age 69 ± 9 years, 55 women [58%]; 40 with nonfluent variant PPA [nfvPPA], 35 with semantic variant PPA [svPPA], 20 with logopenic variant PPA [lvPPA]), of whom 82 underwent brain MRI and 34 had a follow-up visit after 10.2 months. Each model distinguished svPPA from the other PPA groups with high accuracy (R2 range 0.93-1.00; p < 0.001). No differences in accuracy were observed among models for this distinction. In differentiating nfvPPA and lvPPA groups, the models incorporating speech parameters (R2 = 0.92; p < 0.001), GMVs (R2 = 0.95; p < 0.001), and their combination (speech + GMVs; R2 = 0.97; p < 0.001) outperformed those using only standard language scores (R2 = 0.75; p = 0.01). Over time, patients with nfvPPA showed more phonological errors, the svPPA group exhibited more semantic and morphosyntactic errors along with difficulties in naming and syntax production, and patients with lvPPA exhibited reduced number of words per second and fewer words per sentence. Discussion All models were equally effective in distinguishing the svPPA group from the other 2 PPA subtypes. However, compared with using standard measures alone, incorporating speech measures from the “Picnic Scene” speech test, GMVs, or their combination into the models significantly improved accuracy in differentiating nfvPPA and lvPPA groups. The PPA variants showed distinct speech trajectories. These variables can aid in understanding disease progression, predicting patient outcomes, and planning speech therapy interventions in clinical practice
Conventional and new immunotherapies for immune system dysregulation in postpartum mood disorders: comparisons to immune system dysregulations in bipolar disorder, major depression, and postpartum autoimmune thyroid disease
Full text linkIntroduction: Postpartum mood disorders are heterogenous disorders and comprise postpartum psychosis and postpartum depression. Evidence is accumulating that systemic monocyte/macrophage activation, low-grade inflammation and (premature senescence related) T cell defects increase the risk for mood disorders outside pregnancy by affecting the function of microglia and T cells in the emotional brain (the cortico-limbic system) leading to inadequate mood regulation upon stress. Areas covered: The evidence in the literature that similar immune dysregulations are present in postpartum mood disorders. Results: The physiological postpartum period is characterized by a rapid T cell surge and a mild activation of the monocyte/macrophage system. Postpartum mood disorder patients show a diminished T cell surge (including that of T regulatory cells) and an increase in low grade inflammation, that is, an increased inflammatory state of monocytes/macrophages and higher levels of serum pro-inflammatory cytokines. Expert opinion: Anti-inflammatory agents (e.g. COX-2 inhibitors) and T cell boosting agents (e.g. low-dose IL-2 therapy) should be further investigated as treatment. The hypothesis should be investigated that postpartum mood disorders are active episodes (triggered by changes in the postpartum immuno-endocrine milieu) in ongoing, dynamically fluctuating aberrant neuro-immune-endocrine trajectories leading to mood disorders in women (inheritably) vulnerable to these disorders