Salehhamilton7415

We aimed to investigate changes in regional cerebral blood flow (rCBF) using arterial spin labelling (ASL) in patients with visual snow syndrome (VSS), in order to understand more about the underlying neurobiology of the condition, which remains mostly unknown.

We performed an MRI study in which whole-brain maps of rCBF were obtained using pseudo-continuous ASL. Twenty-four patients with VSS and an equal number of gender and age-matched healthy volunteers took part in the study. All subjects were examined with both a visual paradigm consisting of a visual-snow like stimulus, simulating key features of the snow, and a blank screen at rest, randomly presented.

Patients with VSS had higher rCBF than controls over an extensive brain network, including the bilateral cuneus, precuneus, supplementary motor cortex, premotor cortex and posterior cingulate cortex, as well as the left primary auditory cortex, fusiform gyrus and cerebellum. These areas were largely analogous comparing patients either at rest, or when looking at a 'snow-like' visual stimulus. This widespread, similar pattern of perfusion differences in either condition suggests a neurophysiological signature of visual snow. Furthermore, right insula rCBF was increased in VSS subjects compared with controls during visual stimulation, reflecting a greater task-related change and suggesting a difference in interoceptive processing with constant perception of altered visual input.

The data suggest VSS patients have marked differences in brain processing of visual stimuli, validating its neurobiological basis.

The data suggest VSS patients have marked differences in brain processing of visual stimuli, validating its neurobiological basis.

Four ablative neurosurgical procedures are used in the treatment of refractory psychiatric illness. The long-term effects of these procedures on psychiatric symptoms across disorders has never been synthesised and meta-analysed.

A preregistered systematic review was performed on studies reporting clinical results following ablative psychiatric neurosurgery. Four possible outcome measures were extracted for each study depression, obsessive-compulsive symptoms, anxiety and clinical global impression. Effect sizes were calculated using Hedge's g. Equipercentile linking was used to convert symptom scores to a common metric. The main outcome measures were the magnitude of improvement in depression, obsessive compulsive symptoms, anxiety and clinical global impression. The secondary outcome was a subgroup analysis comparing the magnitude of symptom changes between the four procedures.

Of 943 articles, 43 studies reporting data from 1414 unique patients, were included for pooled effects estimates with a random-effects meta-analysis. Results showed that there was a large effect size for improvements in depression (g=1.27; p<0.0001), obsessive-compulsive symptoms (g=2.25; p<0.0001) and anxiety (g=1.76; p<0.0001). The pooled clinical global impression improvement score was 2.36 (p<0.0001). On subgroup analysis, there was only a significant degree of heterogeneity in effect sizes between procedure types for anxiety symptoms, with capsulotomy resulting in a greater reduction in anxiety than cingulotomy.

Contemporary ablative neurosurgical procedures were significantly associated with improvements in depression, obsessive-compulsive symptoms, anxiety and clinical global impression.

CRD42020164784.

CRD42020164784.

Cough severity represents an important subjective endpoint in assessing the effectiveness of therapies for patients with chronic cough. Although cough-specific quality of life questionnaires exist, a widely available cough severity instrument with established measurement properties remains unavailable.

To identify and summarise the results of studies reporting on the experience of patients with chronic cough and, in the process, develop a conceptual framework to inform development of a patient-reported outcome measurement (PROM) addressing cough severity.

We identified 61 eligible studies reporting on patient experience with chronic cough. Studies provided 82 potential items, of which 43 proved unique and relevant to cough severity. The urge-to-cough sensation and the cough symptom itself represented broad domains of cough severity. Two subdomains under urge-to-cough included frequency (1 item) and intensity (1 item). Five subdomains under cough symptoms included control (2 items), frequency (6 items), bout duration (1 item), intensity (8 items), and associated features/sequelae (24 items).

Our systematic survey and conceptual framework identified items and domains of cough severity in patients with refractory or unexplained chronic cough. The results support item generation and content validity for a PROM assessing cough severity.

Our systematic survey and conceptual framework identified items and domains of cough severity in patients with refractory or unexplained chronic cough. The results support item generation and content validity for a PROM assessing cough severity.Small cell lung cancer (SCLC) comprises about 15% of all lung cancers. It is an aggressive disease, with early metastasis and a poor prognosis. Until recently, SCLC treatment remained relatively unchanged, with chemotherapy remaining the cornerstone of treatment. In this overview we will highlight the recent advances in the field of staging, surgery, radiotherapy and systemic treatment. Nevertheless, the prognosis remains dismal and there is a pressing need for new treatment options. We describe the progress that has been made in systemic treatment by repurposing existing drugs and the addition of targeted treatment. In recent years, immunotherapy entered the clinic with high expectations of its role in the treatment of SCLC. Unravelling of the genomic sequence revealed new possible targets that may act as biomarkers in future treatment of patients with SCLC. Hopefully, in the near future, we will be able to identify patients who may benefit from targeted therapy or immunotherapy to improve prognoses.COPD is diagnosed and evaluated by pulmonary function testing (PFT). Chest computed tomography (CT) primarily serves a descriptive role for diagnosis and severity evaluation. CT densitometry-based emphysema quantification and lobar fissure integrity assessment are most commonly used, mainly for lung volume reduction purposes and scientific efforts.A shift towards a more quantitative role for CT to assess pulmonary function is a logical next step, since more, currently underutilised, information is present in CT images. For instance, lung volumes such as residual volume and total lung capacity can be extracted from CT; these are strongly correlated to lung volumes measured by PFT.This review assesses the current evidence for use of quantitative CT as a proxy for PFT in COPD and discusses challenges in the movement towards CT as a more quantitative modality in COPD diagnosis and evaluation. To better understand the relevance of the traditional PFT measurements and the role CT might play in the replacement of these parameters, COPD pathology and traditional PFT measurements are discussed.

Asthma exacerbations in children is one of the most common medical conditions requiring urgent visits to primary healthcare providers or emergency departments, and even hospitalisations. Currently, there is significant variation in the management of asthma exacerbations expressed in guideline recommendations

clinical practice. This disconnect affects diagnostic and treatment decisions for the clinician and patient.

We systematically reviewed the available guidelines providing recommendations for diagnostic and therapeutic management of asthma exacerbations in the paediatric population.

A systematic review of the literature for guidelines published between January 2009 and October 2019 was conducted, using a protocol registered with the international prospective register of systematic reviews (PROSPERO CRD42020221562).

16 asthma exacerbation clinical practice guidelines for children were included. Despite general agreement between guidelines on the definition of asthma exacerbation, there was great variability in the definition of disease severity and assessment of asthma control. This systematic review also highlighted a paucity of recommendations for criteria for hospitalisation and discharge. Many guidelines scored poorly when measured for stakeholder involvement and editorial independence.

Comprehensive and updated guidelines compliant with international standards for clinical guidelines may significantly improve clinical practice quality, promote evidence-based recommendations and provide uniformity of treatment between countries.

Comprehensive and updated guidelines compliant with international standards for clinical guidelines may significantly improve clinical practice quality, promote evidence-based recommendations and provide uniformity of treatment between countries.

As incidence rates for lung cancer are still very high and lung cancer remains the most deadly cancer since the turn of the millennium, efforts have been made to find new approaches in cancer research. This systematic review highlights how therapeutic options were extended and how the development of new drugs has picked up speed during the last 20 years.

A systematic search was performed in PubMed, Cochrane Library and the European Union Trial Register and 443 records were identified. Our inclusion criteria constituted completed phase I, II and III studies investigating drugs approved by the European Medicines Agency (EMA). Overall, 127 articles were analysed.

During the 5 year interval from 2015 to 2020, significantly more drugs were approved after phase III, and occasionally after phase II, trials than between 2000 and 2005 (p=0.002). Furthermore, there was a significant time difference (p=0.00001) indicating an increasingly briefer time interval between the publication of phase I and phase III results in the last few years.

Due to novel therapeutic approaches, numerous new drugs in lung oncology were approved. This has improved symptoms and prognoses in patients with advanced lung cancer. However, faster approval could make it difficult to scrutinise new options regarding safety and efficacy with sufficient diligence.

Due to novel therapeutic approaches, numerous new drugs in lung oncology were approved. CX-5461 mw This has improved symptoms and prognoses in patients with advanced lung cancer. However, faster approval could make it difficult to scrutinise new options regarding safety and efficacy with sufficient diligence.Neuregulin 4 (Nrg4), an adipose tissue-enriched endocrine factor, participates in adipocyte-to-hepatocyte communication, eliciting beneficial metabolic effects in non-alcoholic fatty liver disease (NAFLD). Here, we evaluate the physiological roles of Nrg4 in humans and unravel the role of NRG4 variants in the pathogenesis of NAFLD and related metabolic disorders. We identified two rare missense mutations-p. R44H and p.E47Q- in the NRG4 EGFL domain by whole exome sequencing in 224 severely obese subjects and exome genotyping in 2,388 subjects from Shanghai Obesity Study. The over-expression animal models showed wild-type (WT) Nrg4 could attenuate high-fat diet-induced hepatic lipogenesis and improve energy metabolism. Nrg4 E47Q enhanced the protective effect, whereas Nrg4 R44H lost this function. Unlike Nrg4 R44H, Nrg4 E47Q activated the phosphorylation of ErbB4 and negatively regulated the de novo lipogenesis via the ErbB4-STAT5-SREBP1C pathway. The surface plasmon resonance experiments revealed a higher affinity of E47Q Nrg4 than WT to bind ErbB4, while R44H showed no binding.