Physical exercise in locally advanced pancreatic adenocarcinoma: “If I walk, I live. Although one can die of cancer, now I am living”

The most widely used chemotherapeutic combinations in locally advanced (LA) or metastatic pancreatic ductal adenocarcinoma (PDAC) are Nab-Paclitaxel-Gemcitabine (Nab-PCT-GEM) and Fluorouracil, Folinic acid, Oxaliplatin, and irinotecan (FOLFIRINOX). Chemo-resistance, typical of PDAC, appears to be due to the negative influence of stroma population cells, namely regulatory T cells (Treg) and myeloid-derived suppressor cells, macrophages with inhibitory effects on the antitumor activity of the innate and adaptive immune systems, and resistance to cancer treatment. Among other factors that may influence immune surveillance, constant physical activity appears to reduce the risk of cancer-related mortality and cardiovascular risk. However, this does not seem to increase the survival of patients with PDAC. The exception is our young inoperable patient. For LA head PDAC, he was treated with seven cycles of Nab-PCT-GEM and RT 50 Gy/15 fractions combined to biweekly GEM and salvage FOLFIRINOX. The five-year surviving patient travelled 15,000 km on foot and continues inexorably his "walking therapy"

Pattern of structural and functional brain abnormalities in asymptomatic granulin mutation carriers

To investigate the patterns of brain atrophy, white matter (WM) tract changes, and functional connectivity (FC) abnormalities in asymptomatic granulin (GRN) mutation carriers

Abnormalities in functional connectivity in borderline personality disorder: Correlations with metacognition and emotion dysregulation

A few studies reported functional abnormalities at rest in borderline personality disorder (BPD), but their relationship with clinical aspect is unclear. We aimed to assess functional connectivity (FC) in BPD patients and its association with BPD clinical features. Twenty-one BPD patients and 14 healthy controls (HC) underwent a multidimensional assessment and resting-state fMRI. Independent component analysis was performed to identify three resting-state networks: default mode network (DMN), salience network (SN), and executive control network (ECN). FC differences between BPD and HC were assessed with voxel-wise two-sample t-tests. Additionally, we investigated the mean FC within each network and the relationship between connectivity measures and BPD clinical features. Patients showed significant lower mean FC in the DMN and SN, while, at the local level, a cluster of lower functional connectivity emerged in the posterior cingulate cortex of the DMN. The DMN connectivity was positively correlated with the anger-state intensity and expression, while the SN connectivity was positively correlated with metacognitive abilities and a negative correlation emerged with the interpersonal aggression. The dysfunctional connectivity within these networks might explain clinical features of BPD patients

Age at onset reveals different functional connectivity abnormalities in prodromal Alzheimer's disease

Age at symptom onset (AAO) underlies different Alzheimer's disease (AD) clinical variants: late-onset AD (LOAD) is characterized by memory deficits, while early-onset AD (EOAD) presents predominantly with non-memory symptoms. The involvement of different neural networks may explain these distinct clinical phenotypes. In this study, we tested the hypothesis of an early and selective involvement of neural networks based on AAO in AD. Twenty memory clinic patients with prodromal AD (i.e., mild cognitive impairment with an AD-like cerebrospinal fluid profile) and 30 healthy controls underwent a cognitive evaluation and a resting state functional MRI exam. Independent component analysis was performed to assess functional connectivity (FC) in the following networks: default mode, frontoparietal, limbic, visual, and sensorimotor. Patients were stratified into late-onset (pLOAD) and early-onset (pEOAD) prodromal AD according to the AAO and controls were stratified into younger and older groups accordingly. Decreased FC within the default mode and the limbic networks was observed in pLOAD, while pEOAD showed lower FC in the frontoparietal and visual networks. The sensorimotor network did not show differences between groups. A significant association was found between memory and limbic network FC in pLOAD, and between executive functions and frontoparietal network FC in pEOAD, although the latter association did not survive multiple comparison correction. Our findings indicate that aberrant connectivity in memory networks is associated with pLOAD, while networks underlying executive and visuo-spatial functions are affected in pEOAD. These findings are in line with the hypothesis that the pathophysiological mechanisms underlying EOAD and LOAD are distinct