Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.
Objective Delay in the diagnosis of head and neck cancer can result in significant excess morbidity and mortality. How the pandemic has affected patient presentation in Scotland is unknown. Method This retrospective cohort study compared all presentations of head and neck cancer between June and October of 2019 with the same period following the peak of the pandemic in 2020 in West Scotland, a region populated by 2.5 million people. Results A total of 528 patients met our inclusion criteria. Compared with 2019, patients in 2020 were more likely to present with a higher American Joint Committee on Cancer stage (odds ratio, 1.67 (95 per cent confidence interval = 1.20 to 2.31); p = 0.002), a longer preceding symptom duration (odds ratio, 2.03 (95 per cent confidence interval = 1.44 to 2.87; p < 0.001) and to have an emergency presentation (odds ratio, 2.53, (95 per cent confidence interval = 1.15 to 5.55; p = 0.017). Conclusion Patients are presenting later with more advanced head and neck cancer following the coronavirus disease 2019 pandemic.
Introduction We aim to establish if the first wave of COVID-19 has caused HNC patients to present later or with more advanced disease and if there have been delays in time to imaging, treatment or MDT discussion. Method Patients were identified retrospectively from a database of cases discussed at head and neck MDT between June and October of 2019 and 2020. New HNC cases were included, and benign or recurrent disease excluded. Data was extracted from electronic patient records and statistical comparisons were performed using JASP. Results Data was analysed from 216 patients (2019 n=98, 2020 n=118). No statistically significant differences were observed in age, ECOG, smoking and alcohol use. Significantly more patients presented with >6 weeks history of red flag symptoms in 2020 than 2019 with an odds ratio (OR) of 2.44 (95% CI, 1.38 to 4.23), (p=0.002). Patients in 2020 were also significantly more likely to present as an emergency, OR 5.94 (95% CI 1.31 to 27.02), (p=0.013). The OR of being in a higher AJCC stage in 2020 versus 2019 was 1.69 (95% CI, 1.00 to 2.84), (p=0.05). There were no significant differences in time to MDT discussion, first dedicated imaging, or time to initiation of treatment. Conclusion This data supports concerns that COVID-19 has caused delays in patient presentation, evidenced by longer symptom duration, higher AJCC stage and more emergency presentations. The management was not impacted. HNC services are functioning well despite the pandemic and patients should be encouraged to present to facilitate earlier intervention.
Background Despite operative and adjuvant therapies, glioblastoma remains incurable, with the extent of resection being one of few treatments that can improve survival. To improve resection, operative adjuncts are used, with neuronavigation and 5-aminolevulinic acid (5-ALA) recommended as a standard of care in those aimed for maximal safe resection. Despite the standards, meta-analysis concluded that the impact of 5-ALA on the extent of surgical resection is of low quality due to bias in reporting tumour location and additional image guidance used, factors impacting on extent of resection as well as short-term neurological outcomes being uncertain. Therefore we aimed to evaluate the availability and use of 5-ALA and other adjuncts and compare surgical outcomes of 5-ALA-guided versus non-5-ALA-guided resections. Material and Methods A multicenter prospective observational cohort study was conducted across 27 out of 31 available centres in the UK and Ireland from 6 January until 19 March 2020. Inclusion criteria included adults with first diagnosis, supratentorial glioblastoma undergoing resection. Primary outcomes included: i) the availability and use of surgical adjuncts and ii) complete resection of enhancing tissue (CRET). Secondary outcomes included adverse events, new onset of postoperative neurological deficit and post-operative neurological function. Descriptive and inferential statistics were used for analysis with a p-value <0.05 deemed significant. Results 232 consecutive cases were identified. 142/232 cases were aimed for maximal safe resection subsequently divided into 5-ALA-guided (n=92) versus non-5-ALA-guided (n=50) resections. 5-ALA and neuronavigation were available across all centres. Neuronavigation and 5-ALA were used in 91% (n=129/142) and 65% (n=92/142) of cases aimed for maximal safe resection whereas 83% (n=75/90) and 49% (n=44/90) for debulk surgery. 35 unique combinations of surgical adjuncts were used in 232 operations. 5-ALA-guided resection yielded a higher percentage of CRET than without (55% versus 28%, p < 0.01). The two groups showed no difference in adverse events (p=0.98), new onset of neurological deficit (p=0.88) nor neurological function (p=0.7). A logistic regression analysis showed that 5-ALA was an important predictor of CRET regardless of additional adjuncts used (OR 2.4, CI 0.96-5.97, P = 0.05), tumour location and molecular characterisation (OR 3.48, CI 1.61-7.51, P <0.01). Conclusion Firstly, we showed that 5-ALA is not always used for glioblastoma aimed for CRET. Secondly, we report a great heterogeneity of adjuncts used for resection, possibly explained by a lack of high-quality evidence and surgeon training. Thirdly we demonstrate that 5-ALA-guided resection leads to higher percentage of CRET regardless of other adjuncts used, tumour location and molecular characterisation.
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