IRIS UniSR (’Università Vita-Salute San Raffaele)
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Mapping of current practices of palliative care for patients with heart failure throughout Europe: A scoping review
Full text linkHeart failure (HF) is a growing health and societal challenge in Europe, due to an increasingly elderly, frail and multimorbid population. Many patients with HF experience a high burden of complex and multidimensional symptoms leading to a reduced quality of life and significant socioeconomic impact. Despite proven benefits, the integration of palliative care into HF management pathways remains inconsistent and underutilized. We aim to map how current national and international guidelines recommend integrating palliative care into HF management across the 10 countries represented by the EU-funded RAPHAEL consortium (Horizon Europe programme, No 101137170): Belgium, Germany, Lithuania, the Netherlands, Spain, Italy, Poland, Sweden, Switzerland and the United Kingdom. A systematic search was conducted across six databases (EMBASE, Global Health, MEDLINE, PsycINFO, The Cochrane Library and Web of Science) for publications from 1 January 2000 to 25 May 2024. Eligible publications focused on adults with HF and models of palliative care integration. Data were synthesized using content analysis. Of 1543 records screened, 13 publications were included. Most studies were guidelines, consensus or position papers; only one was qualitative research. The definition of the population with HF eligible for palliative care was heterogeneous and inconsistently defined, mostly by symptoms (4/13 publications; 31%) and pathophysiology (2/13; 15%). The most frequent triggers for palliative care referral were clinical features and symptoms (8/13; 62%), patients approaching the end of life (8/13; 62%), and symptomatic deterioration despite optimal therapy (7/13; 54%). Additional triggers included multiple (>1) unplanned hospitalizations (6/13; 46%) and spiritual, emotional or social issues (7/13; 54%). Outcomes of palliative care referral for HF patients focused on quality of life (9/13; 69%) and symptom control (9/13; 69%). Multiprofessional involvement was emphasized with cardiologists (12/13; 92%), nurses (10/12; 77%), palliative care specialists (9/13; 69%) and primary care physicians (4/13; 31%). Publications generally noted that despite increased awareness and recommendations, referrals remain low and mostly late stages. This review underscores the need for structured, early integration of palliative care in HF management across Europe with clear triggers for palliative care referral, application of standardized pathways and fostering of multiprofessional collaboration. Developing these, while simultaneously addressing implementation challenges through policy development, could improve patient outcomes and quality of life
Cervical spinal cord gray matter damage predicts disability worsening in multiple sclerosis: a longitudinal study
No full textObjective: Cervical spinal cord (cSC) gray matter (GM) damage is associated with current disability in multiple sclerosis (MS), but its prognostic value remains unexplored. We aimed to investigate whether cSC GM damage may predict disability worsening in MS. Materials and methods: Seventy-nine MS patients and 49 healthy controls (HC) underwent 3 T brain and cSC MRI at baseline and two neurological evaluations after median follow-up of 1.3 years. Total and GM cSC lesions were identified on axial T2-weighted sequences, whereas global and GM cSC cross-sectional areas (CSAs) at C3–C4 level were quantified on phase-sensitive inversion recovery sequences. Brain lesional and volumetric measures were also assessed. At follow-up, disability worsening was defined as deterioration on ≥ 1/3 components of the Expanded Disability Status Scale (EDSS)-plus score (EDSS worsening or ≥ 20% change in timed 25-foot walk [T25FWT] or 9-hole peg test [9-HPT]). Results: At follow-up, 40/79 (50.6%) patients showed EDSS-plus worsening, with 13/79 (16.4%) worsening at EDSS score, 13/79 (16.4%) at 9-HPT, and 29/79 (36.7%) at T25FWT. Progressive phenotype (odds ratio [OR] = 8.65) predicted EDSS worsening (p = 0.001, C-index = 0.79). Progressive phenotype (OR = 5.56), lower cortical volume (OR = 0.41), and higher cSC GM T2-hyperintense lesion volume (OR = 2.28) (p ≤ 0.035, C-index = 0.88) predicted 9-HPT worsening. Longer disease duration (OR = 1.64), progressive phenotype (OR = 4.74), and lower cSC GM CSA (OR = 0.51) predicted T25FWT worsening (p ≤ 0.050, C-index = 0.77). Male sex (OR = 6.12), older age (OR = 1.71), progressive phenotype (OR = 7.40), and lower cSC GM CSA (OR = 0.47) predicted EDSS-plus worsening (p ≤ 0.055, C-index = 0.83). Conclusions: cSC GM damage emerged as a relevant MRI predictor of disability worsening in MS, highlighting its prognostic relevance
State of the art and perspectives of gene therapy in heart failure. A scientific statement of the Heart Failure Association of the ESC, the ESC Council on Cardiovascular Genomics and the ESC Working Group on Myocardial & Pericardial Diseases
No full text: Gene therapy has recently become a reality in the treatment of cardiovascular diseases. Strategies to modulate gene expression using antisense oligonucleotides or small interfering RNA are proving to be safe and effective in the clinic. Adeno-associated viral vector-based gene delivery and CRISPR-Cas9-based genome editing have emerged as efficient strategies for gene delivery and repair in humans. Overall, gene therapy holds the promise not only of expanding current treatment options, but also of intervening in previously untackled causal disease mechanisms with little side effects. This scientific statement provides a comprehensive overview of the various modalities of gene therapy used to treat heart failure and some of its risk factors, and their application in the clinical setting. It discusses specifically the possibilities of gene therapy for hereditary heart diseases and (non)-genetic heart failure. Furthermore, it addresses safety and clinical trial design issues and challenges for future regulatory strategies.Gene therapy has recently become a reality in the treatment of cardiovascular diseases. Strategies to modulate gene expression using antisense oligonucleotides or small interfering RNA are proving to be safe and effective in the clinic. Adeno-associated viral vector-based gene delivery and CRISPR-Cas9-based genome editing have emerged as efficient strategies for gene delivery and repair in humans. Overall, gene therapy holds the promise not only of expanding current treatment options, but also of intervening in previously untackled causal disease mechanisms with little side effects. This scientific statement provides a comprehensive overview of the various modalities of gene therapy used to treat heart failure and some of its risk factors, and their application in the clinical setting. It discusses specifically the possibilities of gene therapy for hereditary heart diseases and (non)-genetic heart failure. Furthermore, it addresses safety and clinical trial design issues and challenges for future regulatory strategies
Doppler ultrasound unveils splanchnic arteries ischemia allowing early successful revascularization in symptomatic systemic sclerosis patients
Full text linkBackground: Systemic sclerosis (SSc) is characterized by macro and microvasculopathy, including splanchnic circulation. Chronic mesenteric ischemia (CMI) is a potentially severe condition which can complicate SSc gastrointestinal vasculopathy. Doppler ultrasound (DUS) may be a non-invasive procedure for identifying CMI in symptomatic SSc patients. Objectives: To investigate the capacity of DUS to detect early CMI and the effect of the endovascular approach on CMI-related symptoms. Methods: DUS of splanchnic arteries was performed in symptomatic SSc patients, during routinary outpatient visits. Results: In 6 out of 72 SSc symptomatic patients, DUS suggested a splanchnic vessels stenosis which was confirmed by computed tomography angiography (CTA). After multidisciplinary evaluation in 3 patients a revascularization was performed. Three-monthly clinical and DUS follow-up was negative in all patients. Conclusion: CDU is a useful screening tool for CMI in SSc patients. Revascularization of stenotic mesenteric arteries seems to be a safe and effective procedure
Retromode imaging in vitreoretinal lymphoma
No full textPurpose: The purpose of this study was to evaluate Retromode (Nidek Co., Gamagori, Japan) as an adjunct diagnostic tool in vitreoretinal lymphoma (VRL). By integrating Retromode findings with multimodal imaging, we aimed to enhance lesion detection of VRL lesions in the retina. Methods: This monocentric retrospective pilot study was conducted at the Ocular Oncology unit of San Raffaele Scientific Institute, Milan. Six consecutive patients with biopsy-proven vitreoretinal lymphoma (VRL) were analyzed. Comprehensive retinal examinations and multimodal imaging, encompassing Retromode, pseudocolor fundus photography, fundus autofluorescence (FAF), and optical coherence tomography (OCT). The study specifically focused on the role of Retromode findings used in conjunction with traditional imaging modalities like FAF and OCT to enhance lesion detection associated with VRL. Imaging analysis was conducted using ImageJ software. Results: Retromode identified detailed structural abnormalities in the deep retinal layers and RPE, revealing additional or more widespread lesions compared to FAF imaging. Retromode pinpointed areas affected by VRL for further examination with OCT. However, in patients with vitritis—a common condition in VRL—Retromode did not yield quality images or meaningful information. Conclusion: Retromode imaging proved to be a valuable adjunct in the multimodal imaging approach to VRL. Its capacity to delineate subtle retinal changes facilitates a tailored diagnostic strategy, enhancing lesion detection and characterization in VRL
Impact of postoperative complications on clinical outcomes after gastrectomy for cancer: multicentre study
No full textBackground: To reduce the clinical and economic burden of complications after gastrectomy for gastric cancer, specific complications should be targeted to effectively allocate healthcare resources for quality improvement and preventive measures. The aim of this study was to assess the impact of complications on clinical outcomes. Methods: This was a retrospective multicentre study of patients who underwent (sub)total gastrectomy for gastric or junctional adenocarcinoma at 43 centres in 16 countries between 2017 and 2021. Outcomes were escalation of care, reoperation, prolonged hospital stay (greater than the 75th percentile), readmission, and 30-day mortality. Adjusted relative risks and population attributable fractions were estimated for specific complication-outcome pairs. The population attributable fraction represents the percentage reduction in the frequency of an adverse outcome if a complication could be completely prevented in the population. Results: In total, 7829 patients were included. Postoperative complications occurred in 1884 patients (24.1%). The most frequent complications were pulmonary complications (436 patients (5.6%)), anastomotic leakage (363 patients (4.6%)), and abdominal collection (301 patients (3.8%)). Anastomotic leakage, cardiac complications, and pulmonary complications had the greatest impact on 30-day mortality (population attributable fraction 26.6% (95% c.i. 14.5% to 38.6%), 18.7% (95% c.i. 9.4% to 28.0%), and 15.6% (95% c.i. 12.0% to 30.0%) respectively). Anastomotic leakage and pulmonary complications had the greatest impact on escalation of care (population attributable fraction 26.3% (95% c.i. 20.6% to 32.0%) and 18.4% (95% c.i. 11.7% to 25.2%) respectively), whereas anastomotic leakage and intra-abdominal bleeding had the greatest impact on reoperation (population attributable fraction 31.6% (95% c.i. 26.4% to 36.9%) and 8.5% (95% c.i. 5.5% to 11.5%) respectively). Most of the studied complications contributed to a prolonged hospital stay, whereas the contribution of complications to readmission did not exceed 15.9%. Subgroup analysis showed regional variation in the impact of complications. Conclusion: Anastomotic leakage had the largest overall negative impact on clinical outcomes after gastrectomy for gastric adenocarcinoma. Reducing the incidence of anastomotic leakage and pulmonary complications would have the most impact on the burden of complications
Le “umane rotazioni” tra conatività e metafisica
No full textIl problema del conatus nella concezione metafisica seicentesca e settecentesc
A rapid and robust luciferase-based reporter system to assess SARS-CoV-2 protease activity
No full textDespite effective antiviral drugs that have emerged to combat SARS-CoV-2 infections, novel therapeutic strategies are required to better address the ongoing and future evolutions of the virus. Targeting viral proteases, such as the main protease (Mpro), remains a promising approach. Here, we present a rapid and sensitive luminescence-based reporter system, the i-NSP4/5-Gluc2, to assess Mpro activity. This system employs Gaussia luciferase (Gluc) fused to a pro-interleukin 1β (pro-IL-1β) fragment containing a specific Mpro cleavage site. Upon Mpro cleavage, Gluc is released and secreted, generating a luminescent signal outside the cells. By optimizing the system's design and experimental conditions, we achieved high sensitivity and specificity. The i-NSP4/5-Gluc2 system was validated using the Mpro inhibitor Nirmatrelvir and successfully identified potential Mpro inhibitors from a small library of 46 compounds, as proof of concept. Notably, 13 out of 14 new compounds identified by the i-NSP4/5-Gluc2 assay exhibited potent antiviral activity against live SARS-CoV-2, highlighting the system's accuracy and predictive power. This BSL2-compatible, high-throughput approach facilitates rapid and efficient screening of antiviral compounds, accelerating the development of effective therapeutics against SARS-CoV-2 and future viral pandemics
OCT5k: A dataset of multi-disease and multi-graded annotations for retinal layers
No full textPublicly available open-access OCT datasets for retinal layer segmentation have been limited in scope, often being small in size, specific to a single disease, or containing only one grading. This dataset improves upon this with multi-grader and multi-disease labels for training machine learning-based algorithms. The proposed dataset covers three subsets of scans (Age-related Macular Degeneration, Diabetic Macular Edema, and healthy) and annotations for two types of tasks (semantic segmentation and object detection). This dataset compiled 5016 pixel-wise manual labels for 1672 OCT scans featuring 5 layer boundaries for three different disease classes to support development of automatic techniques. A subset of data (566 scans across 9 classes of disease biomarkers) was subsequently labeled for disease features for 4698 bounding box annotations. To minimize bias, images were shuffled and distributed among graders. Retinal layers were corrected, and outliers identified using the interquartile range (IQR). This step was iterated three times, improving layer annotations’ quality iteratively, ensuring a reliable dataset for automated retinal image analysis