BACKGROUND: Antithrombotic strategies after percutaneous coronary interventions (PCI) in elderly patients on oral anticoagulant therapy (OAT) are debated due to the balance between ischemic and bleeding risks. Recent guidelines recommend early transitioning from triple antithrombotic therapy to dual antithrombotic therapy, but there are limited data on elderly patients. METHODS: We performed a post-hoc age-specific analysis of the PERSEO Registry population aimed to compare clinical features, therapeutic strategies, and outcomes of individuals aged ≥ 80 years and < 80 years who were on OAT and underwent PCI with stent. The primary endpoint was net adverse clinical events at 1-year follow-up. Secondary endpoints included major adverse cardiac and cerebral events (MACCE), major bleeding [Bleeding Academic Research Consortium (BARC) type 3-5], and clinically relevant bleeding (BARC type 2-5). RESULTS: Among the 1234 patients enrolled, 31% of patients were aged ≥ 80 years (84 ± 3 years, 76% males). Compared to younger patients, elderly patients had higher rates of comorbidities such as hypertension, anaemia or chronic kidney disease, and atrial fibrillation was the leading indication for OAT. Elderly patients were more often discharged on dual antithrombotic therapy (23%) compared to younger patients (13%) (P < 0.0001). They experienced higher net adverse clinical events (38% vs. 21%, P < 0.001), MACCE (24% vs. 12%, P < 0.001), as well as higher bleeding rates. Specifically, rates of major bleeding (9% vs. 6%, P = 0.026), and clinically relevant bleeding (21% vs. 12%, P < 0.001) were significantly higher in elderly patients. CONCLUSIONS Elderly patients on OAT undergoing PCI are a particular frail population with higher risk of MACCE and bleeding compared to younger patients despite a less aggressive antithrombotic therapy.

In this study, the effects of Radio Electric Asymmetric Conveyer (REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes (REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage in mice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TO-RGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.
Animals ; Corpus Striatum ; pathology ; Electric Stimulation ; methods ; Inflammation ; pathology ; Male ; Mice ; Nerve Degeneration ; pathology ; Nerve Regeneration ; physiology ; Parkinsonian Disorders ; pathology

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifactorial disorder, involving dysregulation of brain-gut axis. Our aim was to evaluate the neuroendocrine activity in IBS. METHODS: Thirty IBS and 30 healthy volunteers were enrolled. Psychological symptoms were evaluated by questionnaires. Urinary 5-hydroxyindoleacetic acid, plasma serotonin (5-hydroxytryptamine, 5-HT), endothelin, and neuropeptide Y (NPY), and plasma and urinary cortisol levels were evaluated. Fourteen IBS subjects underwent microneurography to obtain multiunit recordings of efferent postganglionic muscle sympathetic nerve activity (MSNA). RESULTS: Prevalent psychological symptoms in IBS were maladjustment (60%), trait (40%) and state (17%) anxiety, obsessive compulsive-disorders (23%), and depressive symptoms (23%). IBS showed increased NPY (31.9 [43.7] vs 14.8 [18.1] pmol/L, P = 0.006), 5-HT (214.9 [182.6] vs 141.0 [45.5] pg/mL, P = 0.010), and endothelin [1.1 [1.4] vs 2.1 [8.1] pg/mL, P = 0.054], compared to healthy volunteers. Moreover, plasma NPY, endothelin, cortisol and 5-HT, and urinary 5-hydroxyindoleacetic acid were associated with some psychological disorders (P ≤ 0.05). Despite a similar resting MSNA, after cold pressor test, IBS showed a blunted increase in MSNA burst frequency (+4.1 vs +7.8 bursts/min, P = 0.048; +30.1% vs +78.1%, P = 0.023). Baseline MSNA tended to be associated with urinary cortisol (ρ = 0.557, P = 0.059). Moreover, changes in heart rate after mental stress were associated with urinary cortisol (ρ = 0.682, P = 0.021) and changes in MSNA after mental stress were associated with plasma cortisol (ρ = 0.671, P = 0.024).” CONCLUSION: Higher concentrations of endothelin, NPY, and 5-HT were found to be associated with some psychological disorders in IBS patients together with an altered cardiovascular autonomic reactivity to acute stressors compared to healthy volunteers.
Anxiety ; Autonomic Nervous System ; Depression ; Endothelin-1 ; Endothelins ; Healthy Volunteers ; Heart Rate ; Humans ; Hydrocortisone ; Irritable Bowel Syndrome* ; Neuropeptide Y ; Pilot Projects* ; Plasma ; Serotonin

PURPOSE: The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R²). RESULTS: Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, –2.4 to 3.4) for the median PFS and 0.7 months (range, –5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R²=0.539, p < 0.001) and poor correlation (R=0.169, R²=0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident. CONCLUSION: Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.
Arm ; Biomarkers* ; Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Molecular Targeted Therapy ; Translating

PURPOSE: The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R²). RESULTS: Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, –2.4 to 3.4) for the median PFS and 0.7 months (range, –5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R²=0.539, p < 0.001) and poor correlation (R=0.169, R²=0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident. CONCLUSION: Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.
Arm ; Biomarkers* ; Colorectal Neoplasms* ; Disease-Free Survival ; Humans ; Molecular Targeted Therapy ; Translating