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1.
Artigo em Inglês | MEDLINE | ID: mdl-36707373

RESUMO

BACKGROUND: Atherosclerotic heart disease often remains asymptomatic until presentation with a major adverse cardiovascular event. Primary preventive therapies improve outcomes, but conventional screening often misattributes risk. Vascular imaging can be utilised to detect atherosclerosis, but often involves ionising radiation. The conjunctiva is a readily accessible vascular network allowing non-invasive hemodynamic evaluation. AIM: To compare conjunctival microcirculatory function in patients with and without obstructive coronary artery disease. METHODS: We compared the conjunctival microcirculation of myocardial infarction patients (MI-cohort) to controls with no obstructive coronary artery disease (NO-CAD cohort). Conjunctival imaging was performed using a smartphone and slit-lamp biomicroscope combination. Microvascular indices of axial (Va) and cross-sectional (Vcs) velocity; blood flow rate (Q); and wall shear rate (WSR) were compared in all conjunctival vessels between 5 and 45 µm in diameter. RESULTS: A total of 127 patients were recruited (66 MI vs 61 NO-CAD) and 3602 conjunctival vessels analysed (2414 MI vs 1188 NO-CAD). Mean Va, Vcs and Q were significantly lower in the MI vs NO-CAD cohort (Va 0.50 ± 0.17 mm/s vs 0.55 ± 0.15 mm/s, p < 0.001; Vcs 0.35 ± 0.12 mm/s vs 0.38 ± 0.10 mm/s, p < 0.001; Q 154 ± 116 pl/s vs 198 ± 130 pl/s, p < 0.001). To correct for differences in mean vessel diameter, WSR was compared in 10-36 µm vessels (3268/3602 vessels) and was lower in the MI-cohort (134 ± 64 s-1 vs 140 ± 63 s-1, p = 0.002). CONCLUSIONS: Conjunctival microcirculatory alterations can be observed in patients with obstructive coronary artery disease. The conjunctival microvasculature merits further evaluation in cardiovascular risk screening.

2.
Clin Sci (Lond) ; 137(2): 181-193, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36630537

RESUMO

OBJECTIVE: Existing strategies to identify relevant studies for systematic review may not perform equally well across research domains. We compare four approaches based on either human or automated screening of either title and abstract or full text, and report the training of a machine learning algorithm to identify in vitro studies from bibliographic records. METHODS: We used a systematic review of oxygen-glucose deprivation (OGD) in PC-12 cells to compare approaches. For human screening, two reviewers independently screened studies based on title and abstract or full text, with disagreements reconciled by a third. For automated screening, we applied text mining to either title and abstract or full text. We trained a machine learning algorithm with decisions from 2000 randomly selected PubMed Central records enriched with a dataset of known in vitro studies. RESULTS: Full-text approaches performed best, with human (sensitivity: 0.990, specificity: 1.000 and precision: 0.994) outperforming text mining (sensitivity: 0.972, specificity: 0.980 and precision: 0.764). For title and abstract, text mining (sensitivity: 0.890, specificity: 0.995 and precision: 0.922) outperformed human screening (sensitivity: 0.862, specificity: 0.998 and precision: 0.975). At our target sensitivity of 95% the algorithm performed with specificity of 0.850 and precision of 0.700. CONCLUSION: In this in vitro systematic review, human screening based on title and abstract erroneously excluded 14% of relevant studies, perhaps because title and abstract provide an incomplete description of methods used. Our algorithm might be used as a first selection phase in in vitro systematic reviews to limit the extent of full text screening required.

3.
Clin Med (Lond) ; 23(1): 73-75, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36697015

RESUMO

The mortality and working years lost from liver cirrhosis present a significant challenge both in the UK and globally. The recent British Association for the Study of the Liver (BASL) annual meeting highlighted the inequities present across the UK in terms of the burden of liver disease and access to specialist services. Innovative new ways of working and novel technologies are needed to address the growing demands of the specialty, while bearing in mind the need for sustainable and patient-focused interventions.


Assuntos
Gastroenterologia , Humanos , Fígado , Reino Unido
5.
Int J Cancer ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694401

RESUMO

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers, and genetic markers. A total of 10,126 head and neck cancer cases and 5,254 controls from 5 North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC=0.94, 95%CI=0.92-0.95 in men and AUC=0.92, 95%CI=0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity, and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer. This article is protected by copyright. All rights reserved.

6.
Microvasc Res ; : 104480, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36690270

RESUMO

OBJECTIVE: Coronary microvascular dysfunction (CMD) is a cause of ischaemia with non-obstructive coronary arteries (INOCA). It is notoriously underdiagnosed due to the need for invasive microvascular function testing. We hypothesized that systemic microvascular dysfunction could be demonstrated non-invasively in the microcirculation of the bulbar conjunctiva in patients with CMD. METHODS: Patients undergoing coronary angiography for the investigation of chest pain or dyspnoea, with physiologically insignificant epicardial disease (fractional flow reserve ≥0.80) were recruited. All patients underwent invasive coronary microvascular function testing. We compared a cohort of patients with evidence of CMD (IMR ≥25 or CFR <2.0); to a group of controls (IMR <25 and CFR ≥2.0). Conjunctival imaging was performed using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allows measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. RESULTS: A total of 111 patients were included (43 CMD and 68 controls). There were no differences in baseline demographics, co-morbidities or epicardial coronary disease severity. The mean number of vessel segments analysed per patient was 21.0 ±â€¯12.8 (3.2 ±â€¯3.5 arterioles and 14.8 ±â€¯10.8 venules). In the CMD cohort, significant reductions were observed in axial/cross-sectional velocity, blood flow, wall shear rate and stress. CONCLUSION: The changes in microvascular function linked to CMD can be observed non-invasively in the bulbar conjunctiva. Conjunctival vascular imaging may have utility as a non-invasive tool to both diagnose CMD and augment conventional cardiovascular risk assessment.

7.
Sci Rep ; 13(1): 1011, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653422

RESUMO

Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.


Assuntos
Cinurenina , Neoplasias Pulmonares , Humanos , Cinurenina/metabolismo , Triptofano/metabolismo , Estudos Transversais , Neopterina/metabolismo , NAD , Biomarcadores , Proteína C-Reativa/metabolismo , Inflamação , Interferon gama/metabolismo
8.
Front Oncol ; 12: 1025398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568237

RESUMO

Objective: We aimed to examine brain tumour grade, a marker of biological aggressiveness, tumour size and cancer treatment are associated with cerebrovascular mortality among patients with malignant glioma, the most common and aggressive type of brain tumour. Methods: We conducted a retrospective, observational cohort study using the US National Cancer Institute's state and regional population-based cancer registries. We identified adult patients with glioma in 2000 to 2018 (N=72,916). The primary outcome was death from cerebrovascular disease. Cox regression modelling was used to estimate the associations with cerebrovascular mortality of tumour grade, tumour size and treatment (surgery, radiotherapy, chemotherapy), calculating hazard ratios (HR) adjusted for these factors as well as for age, sex, race, marital status and calendar year. Results: Higher grade (Grade IV vs Grade II: HR=2.47, 95% CI=1.69-3.61, p<0.001) and larger brain tumours (size 3 to <6 cm: HR=1.40, 95% CI=1.03 -1.89, p<0.05; size ≥ 6 cm: HR=1.47, 95% CI=1.02-2.13, p<0.05 compared to size < 3cm) were associated with increased cerebrovascular mortality. Cancer treatment was associated with decreased risk (surgery: HR= 0.60, p<0.001; chemotherapy: HR=0.42, p<0.001; radiation: HR= 0.69, p<0.05). However, among patents surviving five years or more from cancer diagnosis radiotherapy was associated with higher risk of cerebrovascular mortality (HR 2.73, 95% CI 1.49-4.99, p<0.01). Conclusion: More aggressive tumour characteristics are associated with increased cerebrovascular mortality. Radiotherapy increased risk of cerebrovascular mortality five-year after cancer diagnosis. Further research is needed to better understand the long-term cardiovascular consequences of radiation therapy, and whether the consequent risk can be mitigated.

9.
Clin Interv Aging ; 17: 1811-1820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532948

RESUMO

Hepatitis B virus (HBV) infection is a major global public health challenge associated with significant morbidity and mortality. Due to worldwide population aging, HBV infection in the elderly will become increasingly prevalent. Effective universal vaccination programs exist but these are largely targeted towards the younger population. Therefore, the elderly population remains at risk of higher disease burden. New diagnoses of HBV infection in the elderly are usually asymptomatic chronic infections which increases their risk of developing cirrhosis, hepatocellular carcinoma, and liver disease-related mortality, especially if left untreated. Physiological changes and the increasing prevalence of multimorbidity associated with aging also potentially worsen outcomes in elderly patients with chronic HBV infection. Therefore, this cohort of patients should be monitored closely and effectively. Current international clinical practice guidelines unfortunately do not provide hard treatment endpoints specific to elderly patients with chronic HBV infection. Management of these patients is complex and requires an individualized approach. Multiple factors such as physiological changes, comorbidities, compliance, treatment tolerability and efficacy, burden of treatment, and realistic treatment goals need to be considered. Shared decision-making between patient and clinician is essential to ensure that the final decision for or against treatment aligns with the patient's values and preferences. This review article aims to summarize the monitoring and management of chronic HBV infection in the aging population.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Humanos , Idoso , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Vírus da Hepatite B/fisiologia , Envelhecimento
10.
Elife ; 112022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36476408

RESUMO

Extrachromosomal DNA (ecDNA) are frequently observed in human cancers and are responsible for high levels of oncogene expression. In glioblastoma (GBM), ecDNA copy number correlates with poor prognosis. It is hypothesized that their copy number, size, and chromatin accessibility facilitate clustering of ecDNA and colocalization with transcriptional hubs, and that this underpins their elevated transcriptional activity. Here, we use super-resolution imaging and quantitative image analysis to evaluate GBM stem cells harbouring distinct ecDNA species (EGFR, CDK4, PDGFRA). We find no evidence that ecDNA routinely cluster with one another or closely interact with transcriptional hubs. Cells with EGFR-containing ecDNA have increased EGFR transcriptional output, but transcription per gene copy is similar in ecDNA compared to the endogenous chromosomal locus. These data suggest that it is the increased copy number of oncogene-harbouring ecDNA that primarily drives high levels of oncogene transcription, rather than specific interactions of ecDNA with each other or with high concentrations of the transcriptional machinery.


Assuntos
Oncogenes , Células-Tronco , Humanos , Oncogenes/genética , DNA
11.
Cell Genom ; 2(11): None, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36388765

RESUMO

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues.

12.
Br J Cancer ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434155

RESUMO

BACKGROUND: Body mass index (BMI) is known to influence the risk of various site-specific cancers, however, dissecting which subcomponents of this heterogenous risk factor are predominantly responsible for driving disease effects has proven difficult to establish. We have leveraged tissue-specific gene expression to separate the effects of distinct phenotypes underlying BMI on the risk of seven site-specific cancers. METHODS: SNP-exposure estimates were weighted in a multivariable Mendelian randomisation analysis by their evidence for colocalization with subcutaneous adipose- and brain-tissue-derived gene expression using a recently developed methodology. RESULTS: Our results provide evidence that brain-tissue-derived BMI variants are predominantly responsible for driving the genetically predicted effect of BMI on lung cancer (OR: 1.17; 95% CI: 1.01-1.36; P = 0.03). Similar findings were identified when analysing cigarettes per day as an outcome (Beta = 0.44; 95% CI: 0.26-0.61; P = 1.62 × 10-6), highlighting a possible shared aetiology or mediator effect between brain-tissue BMI, smoking and lung cancer. Our results additionally suggest that adipose-tissue-derived BMI variants may predominantly drive the effect of BMI and increased risk for endometrial cancer (OR: 1.71; 95% CI: 1.07-2.74; P = 0.02), highlighting a putatively important role in the aetiology of endometrial cancer. CONCLUSIONS: The study provides valuable insight into the divergent underlying pathways between BMI and the risk of site-specific cancers.

13.
Neurooncol Adv ; 4(Suppl 2): ii4-ii5, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36380870
14.
Circ Arrhythm Electrophysiol ; : e011263, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36441561

RESUMO

BACKGROUND: The implications of a drug-induced type 1 Brugada ECG pattern following sodium channel blocker provocation (SCBP) are not fully understood. METHODS: Baseline clinical and ECG data were obtained from consecutive unexplained cardiac arrest survivors undergoing SCBP at 3 centers. A further 15 SCBP positive (SCBP+) unexplained cardiac arrest survivors were recruited from 3 additional centers to explore ventricular fibrillation recurrence. RESULTS: A total of 121 consecutive unexplained cardiac arrest survivors underwent SCBP. The yield of the drug-induced type 1 Brugada ECG pattern was 17%. A baseline type 2/3 Brugada pattern (T2/3BP) (adjusted odds ratio, 19.36 [2.74-136.61]; P=0.003) and PR interval (odds ratio, 1.03 [1.01-1.05] per ms; P=0.017) were independent predictors of SCBP+ response. A pathogenic SCN5A variant was identified in 36% of the SCBP+ group versus 0% in the SCBP- group (P<0.001). Amongst SCBP+ patients, a spontaneous type 1 Brugada pattern was identified in 19% during follow up and in 24% a type 1 Brugada pattern was identified in a relative. Prior syncope (adjusted hazard ratio, 3.83 [1.36-10.78]; P=0.011) and the presence of global early repolarization (hazard ratio, 7.91 [3.22-19.44]; P<0.001) were independent predictors of 5-year ventricular fibrillation recurrence. There was a nonsignificant trend toward greater 5-year ventricular fibrillation recurrence in the SCBP- group (23/95 [24%] versus 3/34 [9%]; P=0.055). CONCLUSIONS: The yield of the drug-induced type 1 Brugada ECG pattern in consecutive unexplained cardiac arrest survivors undergoing SCBP is 17%. A baseline T2/3BP and PR interval were independent predictors of the drug-induced type 1 Brugada ECG pattern. Greater heritability of BrS phenotype in this group was evidenced by a greater prevalence of pathogenic SCN5A variants and relatives with a type 1 Brugada pattern. A history of prior syncope and the presence of global early repolarization were independent predictors of ventricular fibrillation recurrence.

15.
Nutr Cancer ; : 1-11, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36426640

RESUMO

Head and neck cancer (HNC) significantly impacts nutritional status because the tumor limits swallowing function. In this sense, it is important to monitor the nutritional status throughout the life of any individual. A multicenter case-control study was carried out to analyze the BMI at 30 years of age, two years before diagnosis and at the time of diagnosis of individuals with oral cavity, oropharynx, and larynx cancers. It was observed that a 5% reduction in BMI during the two years before enrollment was associated with an increased risk of the oral cavity (OR = 3.73), oropharyngeal OR = 5.25), and laryngeal (OR = 5.22). Reduced BMI of more than 5% over two years before diagnosis was associated with HNC. Weight loss remained significant at diagnosis, but it is not possible to exclude reverse causality since most cases are at an advanced stage. BMI monitoring of individuals at potential risk for HNC can promote early diagnosis and nutritional interventions for HNC.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36433627

RESUMO

BACKGROUND: Frailty is a known predictor of outcome and mortality in patients undergoing liver transplantation. However, most patients remain unsuitable transplant candidates. It is not yet known if the assessment of frailty in non-transplant candidates can aid prognostication. AIM: To collate and interrogate the various frailty tools presently used to predict mortality in the non-transplant cirrhosis setting. METHODS: A comprehensive review of MEDLINE and EMBASE databases for articles published from inception to March 2022 was undertaken, excluding those where patients underwent transplantation or had hepatocellular carcinoma. RESULTS: We identified 12 observational cohort studies, featuring 9 frailty indices. These were from various global healthcare settings and of fair or good quality. Most were objective tools utilising clinician-based assessments. All frailty scores predicted prognosis, with variability in the method of application, and utilisation in long- or short-term mortality. Three studies directly compared different indices in the same population. There was some evidence that simple tools could perform as well, if not better, than more complex, time-consuming scores. CONCLUSIONS: Various frailty tools can reproducibly evaluate mortality in patients with cirrhosis who are ineligible for transplant. However, further prospective head-to-head comparative studies are needed. In addition to determining model utility, studies should focus on important relative considerations which may limit widespread implementation including, ease of use and limited resources, given the global disparity of liver care provision. These tools may positively identify specific patient cohorts at risk of impending deterioration, thereby stratifying those patients likely to benefit from early integration with palliative care.

17.
Leukemia ; 36(12): 2835-2844, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36273105

RESUMO

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.


Assuntos
Predisposição Genética para Doença , Linfoma não Hodgkin , Humanos , Estudo de Associação Genômica Ampla , Fatores de Risco , Linfoma não Hodgkin/genética , Células Germinativas , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único
18.
Int J Cancer ; 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36214797

RESUMO

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36220949

RESUMO

PURPOSE: Due to the risk of intracranial aneurysm (IA) recurrence and the potential requirement for re-treatment following endovascular treatment (EVT), radiological follow-up of these aneurysms is necessary. There is little evidence to guide the duration and frequency of this follow-up. The aim of this study was to establish the current practice in neurosurgical units in the UK and Ireland. METHODS: A survey was designed with input from interventional neuroradiologists and neurosurgeons. Neurovascular consultants in each of the 30 neurosurgical units providing a neurovascular service in the UK and Ireland were contacted and asked to respond to questions regarding the follow-up practice for IA treated with EVT in their department. RESULTS: Responses were obtained from 28/30 (94%) of departments. There was evidence of wide variations in the duration and frequency of follow-up, with a minimum follow-up duration for ruptured IA that varied from 18 months in 5/28 (18%) units to 5 years in 11/28 (39%) of units. Young patient age, previous subarachnoid haemorrhage and incomplete IA occlusion were cited as factors that would prompt more intensive surveillance, although larger and broad-necked IA were not followed-up more closely in the majority of departments. CONCLUSIONS: There is a wide variation in the radiological follow-up of IA treated with EVT in the UK and Ireland. Further standardisation of this aspect of patient care is likely to be beneficial, but further evidence on the behaviour of IA following EVT is required in order to inform this process.

20.
J Clin Transl Hepatol ; 10(5): 939-946, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36304513

RESUMO

The pathogenesis of metabolic-associated fatty liver disease (MAFLD) is complex and thought to be dependent on multiple parallel hits on a background of genetic susceptibility. The evidence suggests that MAFLD progression is a dynamic two-way process relating to repetitive bouts of metabolic stress and inflammation interspersed with endogenous anti-inflammatory reparative responses. In MAFLD, excessive hepatic lipid accumulation causes the production of lipotoxins that induce mitochondrial dysfunction, endoplasmic reticular stress, and over production of reactive oxygen species (ROS). Models of MAFLD show marked disruption of mitochondrial function and reduced oxidative capacitance with impact on cellular processes including mitophagy, oxidative phosphorylation, and mitochondrial biogenesis. In excess, ROS modify insulin and innate immune signaling and alter the expression and activity of essential enzymes involved in lipid homeostasis. ROS can also cause direct damage to intracellular structures causing hepatocyte injury and death. In select cases, the use of anti-oxidants and ROS scavengers have been shown to diminish the pro-apoptopic effects of fatty acids. Given this link, endogenous anti-oxidant pathways have been a target of interest, with Nrf2 activation showing a reduction in oxidative stress and inflammation in models of MAFLD. Thyroid hormone receptor ß (THRß) agonists and nuclear peroxisome proliferation-activated receptor (PPAR) family have also gained interest in reducing hepatic lipotoxicity and restoring hepatic function in models of MAFLD. Unfortunately, the true interplay between the clinical and molecular components of MAFLD progression remain only partly understood. Most recently, multiomics-based strategies are being adopted for hypothesis-free analysis of the molecular changes in MAFLD. Transcriptome profiling maps the unique genotype-phenotype associations in MAFLD and with various single-cell transcriptome-based projects underway, there is hope of novel physiological insights to MAFLD progression and uncover therapeutic targets.

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