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In those without distant metastases at time of salvage surgery (n = 46), DSS at 5, 10, and 15 years was 47%, 38%, and 35%, respectively, median 60 months. Negative resection margin (R0) was independently predictive of superior outcomes. In patients with M0 disease who had R0 resection (n = 37), DSS at 5, 10 and 15 years was 58%, 47%, and 44%, respectively, median 73 months. No patient developed re-recurrence after 5.5 years. CONCLUSIONS This study demonstrates exceptionally durable long-term cancer-free survival following salvage surgery for LRRC, indicating that cure is possible. BACKGROUND Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach. METHODS All rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders were identified using Cox regression analyses. RESULTS From 210 patients, 155 patients had surgery. The three main types of surgery were local tumour resection (LTR, n = 46), low anterior resection (LAR, n = 31) and abdomino-perineal resection (APR, n = 32). Selleck Ruboxistaurin Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Local recurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences were found in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours were smaller, while LAR and APR patients more often received perioperative imatinib. General hospitals treated smaller GISTs, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for local recurrence was higher age (HR 1.06, CI 1.00-1.12, p = 0.048). CONCLUSIONS In European clinical practice for rectal GIST, LTR, LAR and APR have comparable local control. Multimodal approach is higher and tumour rupture less frequent in specialist centres compared to general hospitals. This study investigated the clinicopathological relationship between cognitive dysfunction and Lewy body-related pathology (LRP), and the role of Alzheimer's disease neuropathologic change (ADNC) in affecting this relationship in the Chinese population. A total of 127 brains with antemortem cognition assessment were collected. The postmortem neuropathological classification of LRP and staging of ADNC were evaluated. Pairwise correlation and ordered logistic regression analysis showed that LRP had a moderate correlation with Global Everyday Cognition scores. The proportion of the people with intermediate and high levels of comorbid ADNC increased with the deterioration of LRP. The fit of the cognition prediction model improved when we incorporated both LRP and ADNC into the model compared with LRP alone. Our study indicated that comorbid ADNC can variably present in patients with Lewy body disease. A combination of LRP and concurrent ADNC improves the prediction of cognitive dysfunction compared with LRP alone. These findings may suggest the potential benefit of combined therapeutic approaches targeting concurrent pathological pathways for the Lewy body diseases in the Chinese population. Higher levels of body fat have shown adverse effects on multiple aspects of health, including cognitive and neuroanatomical changes. We tested the relationships of body fat levels and cholesterol to longitudinal age trajectories of subcortical gray matter volume (SCV), hippocampal volume (HCV), and episodic memory. Body fat was indexed by a concerted factor of BMI, visceral adipose tissue, percentage body fat, and total fat mass and was included in the analyses as a cross-sectional measure. We hypothesized that higher level of body fat would be related to steeper age trajectories of SCV, HCV, and memory. The sample consisted of 581 participants (20-83 years) with 942 magnetic resonance imaging and 945 memory examinations. Using generalized additive mixed models, a negative effect of body fat was found on SCV, HCV, and memory. Age and body fat interacted in their association with brain volume change. The results suggest that among cognitively healthy adults, there is a negative effect of higher body fat on SCV, HCV, and memory decline, an effect that increased with age for the neuroanatomical volumes. The etiology and pathogenesis of Parkinson's disease (PD) are tightly linked to the gain-of-function of α-synuclein. However, gradual accumulation of α-synuclein aggregates in dopaminergic neurons of substantia nigra pars compacta (SNpc) leads to the depletion of the functional pool of soluble α-synuclein, and therefore, creates loss-of-function conditions, particularly in presynaptic terminals of these neurons. Studies of how this late-onset depletion of a protein involved in many important steps of neurotransmission contributes to PD progression and particularly, to worsening the nigrostriatal pathology at late stages of the disease are limited and obtained data, are controversial. Recently, we produced a mouse line for conditional knockout of the gene encoding α-synuclein, and here we used its tamoxifen-inducible pan-neuronal inactivation to study consequences of the adult-onset (from the age of 6 months) and late-onset (from the age of 12 months) α-synuclein depletion to the nigrostriatal system. No signio already existing pathology. Cognitive impairments and circadian rhythm disorders are the main clinical manifestations of Alzheimer's disease (AD). Orexin has been reported as abnormally elevated in the cerebrospinal fluid of AD patients, accompanied with cognitive impairments. Our recent research revealed that suvorexant, a dual orexin receptor antagonist, could improve behavioral circadian rhythm disorders in 9-month-old APP/PS1 mice. Here we further observed whether suvorexant could ameliorate the cognitive decline in APP/PS1 mice by using behavioral tests, and investigated the possible mechanisms by in vivo electrophysiological recording, western blot, and immunochemistry. The results showed that suvorexant treatment effectively ameliorated the cognitive impairments, alleviated in vivo hippocampal long-term potentiation suppression, restored the circadian phosphorylated CREB expression in the hippocampus, and reduced amyloid-β protein deposition in the hippocampus and cortex in APP/PS1 mice. These results indicate that the neuroprotective effects of suvorexant against AD are involved in the reduction of amyloid-β plaques, improvement of synaptic plasticity, and circadian expression of phosphorylated CREB, suggesting that suvorexant could be beneficial to the prevention and treatment of AD.
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