IRIS UniSR (’Università Vita-Salute San Raffaele)
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Clinical practice guidelines for the management of non-functioning advanced GEP-NENs: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology (AIOM) in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET)
No full textNeuroendocrine neoplasms (NENs) of the gastroenteropancreatic (GEP) tract represent a rare and heterogeneous group of malignancies. They are distinguished into well-differentiated and poorly differentiated neoplasms, with clinical behavior ranging from relatively indolent to fast-growing, respectively. Surgery is the curative option for localized disease, especially in well-differentiated neoplasms, while various systemic therapies are approved and clinically available for advanced disease. However, considering the complexity of these malignancies, the choice of therapeutic strategy must take into account multiple factors, such as histological diagnosis, primary site, extent of disease, evolution features, functional status, patients and treatment characteristics, treatment availability, and safety profile. A multidisciplinary approach dedicated to NENs and conducted by experienced teams is therefore strongly recommended. Since 2013, the Italian Association of Medical Oncology (AIOM), in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET), has produced guidelines using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach for assessing the certainty of evidence. This updated version (2024) summarized the main diagnostic and therapeutic decision-making processes on specific topics selected by a panel of experts from the AIOM, ITANET, and other national scientific societies with the aim of guiding clinicians in the diagnosis, treatment, and monitoring of patients with GEP-NENs. The integration of these guidelines into daily clinical practice is expected to improve patient care and drive the evolving landscape of GEP-NEN management
Predicting the need for step-up after EUS-guided drainage of peripancreatic fluid collections, including Quadrant-Necrosis-Infection score validation: A prospective cohort study
No full textBackground and Aims: Factors predicting the need for step-up procedures after endoscopic ultrasound (EUS)–guided fluid collection drainage (EUS-FCD) of peripancreatic fluid collections (PFCs) were explored in retrospective studies restricted to walled-off necrosis (WON) and lumen apposing metal stents (LAMSs). Methods: All consecutive candidates for EUS-FCD from 2020 to 2024 were included in a Prospective Registry of Therapeutic EUS (PROTECT, NCT04813055), with prospective monthly follow-up evaluating clinical success, adverse events, and recurrences. Prospectively assessed baseline clinical and morphologic factors, including the Quadrant-Necrosis-Infection (QNI) classification, were included in a stepwise logistic regression model to predict the need for step-up. The agreement between EUS and radiology in assessing the extent of necrosis was compared with the use of Cohen's kappa. Results: Seventy patients (29 postsurgical collections, 21 pseudocysts, and 20 WONs) were treated with double-pigtail plastic stents (DPPSs) in 59% of cases and LAMSs in 41%. Clinical success was 92.9%, with a need for step-up (mostly endoscopic necrosectomy) in 35.7% of cases. Necrosis ≥60% (odds ratio [OR], 7.7; 95% confidence interval [CI], 1.4-43) and being in the high-risk QNI group (OR, 4.6; 95% CI, 1.4-15) were the only independent predictors of any step-up. The same factors predicted the endoscopist's decision to allocate PFCs to LAMSs vs DPPS. The high-risk QNI group was associated with a significantly longer hospital stay (12 days vs 4 days; P = .004). EUS tended to upscale the necrotic content compared with preprocedural radiology (κ = 0.31). Conclusions: The extent of necrosis and the QNI classification strongly correlated with the need for step-up and allocation to LAMS versus DPPS drainage, suggesting a central role in treatment personalization
TSPO PET in multiple sclerosis: Emerging insights into pathophysiology, prognosis, and treatment monitoring
No full textMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and neurodegeneration. The 18 kDa translocator protein (TSPO) is overexpressed on activated microglia, a key mediator of acute and chronic inflammation in MS. Positron emission tomography (PET) targeting TSPO enables in vivo detection of microglial activation in MS, revealing a high proportion of active white matter (WM) lesions. It also detects a substantial innate immune activation within normal-appearing white matter (NAWM), gray matter (GM), choroid plexus (CP), and meninges. In MS patients, increased TSPO binding correlates with clinical disability and brain atrophy, particularly of thalami and other deep GM structures, and predicts disease progression. TSPO PET also shows promise for monitoring responses to disease-modifying therapies (DMTs), and for detecting early signs of opportunistic infections, such as progressive multifocal leukoencephalopathy (PML). Integration with advanced MRI techniques and novel tracers beyond TSPO is likely to further improve our understanding of MS pathophysiology. Despite current limitations, including genetic polymorphisms affecting tracer binding and technical barriers to clinical implementation, TSPO PET may also represent a promising outcome measure for future treatments targeting microglia. Here, we critically review how PET targeting TSPO advances our understanding of MS pathophysiology, aids in prognostication, and may contribute to therapeutic monitoring
Coscienze immerse. Che cosa impariamo sull’esistenza umana studiandone le frontiere?
No full textAlthough cognitive science has prompted neuro-philosophical accounts that do away with the ‘Cartesian myth’ of the self, it is suggested that a non-Cartesian conception of the self can be defended which conceives of the self as the result of an agent’s effort to provide consistency in their thoughts and actions. Such a conception is inherently embodied and rejects the neuro-philosophical myth of the conscious brain in a vat. Moreover, it casts some doubt on the ease with which it is declared that persistently unconscious life is unworthy of living and should not be prolonged
Metabolic Parkinson’s disease
No full textParkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in the substantia nigra. While most cases are sporadic, there is growing evidence of a link between PD and metabolic dysfunctions such as type 2 diabetes mellitus, obesity, and metabolic syndrome. Proposed pathogenic mechanisms underlying this overlap include insulin resistance and chronic inflammation. Similar patterns of cellular damage are observed in both metabolic disorders and PD, including mitochondrial dysfunction, impaired autophagy, oxidative stress, endoplasmic reticulum stress, and gut microbiota alterations. Given the current lack of disease-modifying therapies for PD, there is increasing interest in interventions traditionally used to treat metabolic conditions, such as lifestyle and dietary modifications. Notably, antidiabetic drugs like metformin and incretin mimetics have shown beneficial effects in PD due to their neuroprotective and anti-inflammatory properties, their ability to restore insulin sensitivity, and their role in reducing neuronal susceptibility to toxic insults, as demonstrated in both preclinical and clinical studies. Conversely, traditionally antiparkinsonian drugs such as bromocriptine have long been approved for improving glycemic control in diabetes. This cross-efficacy between drugs used for the two conditions may indirectly support the hypothesis of a shared pathogenesis. A deeper understanding of the connections between metabolic disorders and PD could pave the way for novel preventive and therapeutic strategies
Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study
No full textBackgroundIt remains unclear whether there is a difference in overall survival (OS) benefit between (m)FOLFIRINOX and gemcitabine-nab-paclitaxel as preoperative regimens for localised pancreatic adenocarcinoma. This study aimed to investigate the outcome of patients with resected localised pancreatic adenocarcinoma following (m)FOLFIRINOX versus gemcitabine-nab-paclitaxel.MethodsInternational multicentre retrospective study (16 centres, 8 countries, 3 continents), including consecutive patients after pancreatic resection for localised pancreatic adenocarcinoma following 2-6 months preoperative (m)FOLFIRINOX or gemcitabine-nab-paclitaxel (2010-2018). Primary endpoint was OS from start of preoperative chemotherapy. Cox regression analysis was performed to investigate the association of the preoperative chemotherapy regimen with OS, adjusted for confounders at diagnosis.ResultsOverall, 935 patients were included after resection of localised pancreatic adenocarcinoma following preoperative (m)FOLFIRINOX (65%) or gemcitabine-nab-paclitaxel (35%). Preoperative chemotherapy regimen (m)FOLFIRINOX was not associated with OS (HR = 0.83 [95% CI 0.64-1.08]), compared to gemcitabine-nab-paclitaxel. Interaction analysis showed stronger effect of (m)FOLFIRINOX in patients with a lower (i.e., non-elevated/marginally elevated) serum CA19-9 at diagnosis (pinteraction = 0.032).ConclusionThis international study found no OS benefit of preoperative (m)FOLFIRINOX in patients with resected localised pancreatic adenocarcinoma compared to gemcitabine-nab-paclitaxel
