Search Results for: Scoperto nuovo biomarker per il cancro al colon-retto

Objective
To assess the association between educational level and cardiovascular age acceleration metric derived from ECG, and to determine whether this association is mediated by established cardiovascular disease (CVD) risk factors.

Design
Prospective population-based cohort study (the Tromsø Study).

Setting
General population of the Tromsø municipality, Norway.

Participants
The study sample consisted of 4367 participants of the Tromsø Study, who took part in both Tromsø6 (2007–2008) and Tromsø7 (2015–2016), had a 12-lead ECG obtained at Tromsø7 and did not report a history of heart attack, stroke or atrial fibrillation.

Primary outcome measures
-age, a biomarker of cardiovascular ageing, is defined as the difference (in years) between an individual’s ECG-predicted heart age and their chronological age. ECG-predicted heart age was estimated using a previously validated deep neural network.

Results
Our findings indicate an inverse association between education and -age, with a regression coefficient per increment increase in education of –0.24 (95% CI –0.41 to –0.07) in the overall sample, –0.38 (95% CI –0.59 to –0.16) for women and –0.04 (95% CI –0.31 to 0.23) for men. Participants with the highest level of education (university/college for 4 or more years) had the lowest estimated -age with a regression coefficient of –0.69 years (95% CI –1.23 to –0.16) compared with the group with primary education for the overall sample, –1.05 years (95% CI –1.73 to –0.37) for women and –0.15 years (95% CI –1.03 to 0.73) for men. CVD risk factors mediated up to 75% of the association between overall education and -age, and 80% of the association among those with the highest education level (university/college for 4 or more years). Among women, 50% of the effect of overall education on -age was mediated by CVD risk factors, rising to 53% in the category with the highest level of education. However, in the subsample of men, there was no significant association between education and -age, and the mediation analysis produced natural direct and indirect effects pointing in opposite directions.

Conclusions
Cardiovascular ageing is inversely associated with educational level, an effect that appears to be largely mediated through established risk factors.

In campo squadre dei Centri oncoematologia pediatrica d’Italia

Introduction
Delirium is common in the older hospital population and is often precipitated by acute illness. Delirium is associated with poor outcomes including subsequent cognitive decline and dementia and may therefore be a modifiable risk factor for dementia. However, the mechanisms underpinning the delirium–dementia relationship and the role of coexisting acute illness factors remain uncertain. Current biomarker studies of delirium have limitations including lack of detailed delirium characterisation with few studies on neurodegenerative or neuroimaging biomarkers especially in the acute setting. The Oxford and Reading Cognitive Health After Recovery from acute illness and Delirium—Prospective Study (ORCHARD-PS) aims to elucidate the pathophysiology of delirium and subsequent cognitive decline after acute illness in older adults, through acquisition of multimodal biomarkers for deep phenotyping of delirium and acute illness, and follow-up for incident dementia.

Methods and analysis
ORCHARD-PS is a bi-centre, prospective cohort study. Consecutive eligible patients requiring acute hospital admission or assessment are identified by the relevant acute clinical care team. All patients age >65 years without advanced dementia, nursing home residence, end-stage frailty or terminal illness are eligible. Details of potential participants are communicated to the research team and written informed consent or consultee agreement is obtained. Participants are interviewed as soon as possible after admission/assessment using a structured proforma.
Data are collected on demographics, diagnosis and comorbidities, social and functional background. Delirium is assessed using the 4A’s test, Confusion Assessment Method (long-form), Observational Scale of Level of Arousal, Richmond Agitation-Sedation Scale and Memorial Delirium Assessment Scale and diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Delirium is categorised by time of onset (prevalent vs incident), dementia status, motoric subtype, severity and duration. Cognitive tests include the 10-point Abbreviated Mental Test and Montreal Cognitive Assessment. Participants are reassessed every 48–72 hours if remaining in hospital. Informant questionnaire data and interview are supplemented by hand searching of medical records and linkage to electronic patient records for nursing risk assessments, vital observations, laboratory results and International Classification of Diseases, Tenth Revision diagnostic and procedure codes.
In-person follow-up with more detailed cognitive testing and informant interview is undertaken at 3 months, and 1 and 3 years supplemented with indirect follow-up using medical records. Blood banking is performed at baseline and all follow-ups for future biomarker analyses. CT-brain and MRI-brain imaging acquired as part of standard care is obtained for quantification of brain atrophy and white matter disease/stroke supplemented by research CT-brain imaging. Outcomes include length of hospitalisation, change in care needs, institutionalisation, mortality, readmission, longitudinal changes in cognitive and functional status and incident dementia. Biomarker associations with delirium, and with incident dementia on follow-up, will be determined using logistic or Cox regression as appropriate, unadjusted and adjusted for covariates including demographics, baseline cognition, frailty, comorbidity and apolipoprotein E genotype.

Ethics and dissemination
ORCHARD-PS is approved by the South Central—Berkshire Research Ethics Committee (REC Reference: 23/SC/0199). Results will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number
ISRCTN24171810.

Objectives
Systemic immune-inflammation index (SII) is a biomarker of inflammatory conditions; however, no scoring system has been evaluated for predicting mortality in patients with renal failure in intensive care unit (ICU). This study aimed to determine associations between SII level and mortality in patients with renal failure.

Design
Using the Medical Information Mart for Intensive Care IV (V.2.0) database (USA), this retrospective study included 837 patients who were admitted to ICU with end-stage renal disease (ESRD), between 2008 and 2019.

Primary and secondary outcome measures
Cox proportional-hazards models were used to evaluate correlations between SII and outcomes, expressing results as hazard ratios (HRs) with 95% confidence intervals (95% CIs). Regression analysis was used to determine associations between variables and SII.

Results
In total, 837 adult patients from a total of 76 943 patients admitted to ICU were included, comprising 59.60% males with mean age 62.27±14.9 years and mean BMI 28.36±7.43 Kg/m2. Using median SII (1628 X 109 /L) as cut-off value, high (≥ 1628X109 /L) SII was also associated with an increased risk of ICU mortality (HR 1.97 (95% CI 1.15 to 3.35), p=0.034), in-hospital mortality (HR 1.95 (95% CI 1.23 to 3.09), p=0.017) and total mortality (HR 1.30 (95% CI 1.07 to 1.58), p=0.024).

Conclusions
SII may predict mortality in critically ill patients admitted to ICU with ESRD. SII ≥ 1628×109 /L correlates significantly with increased ICU mortality, in-hospital mortality and total mortality.

Introduction
The medical profession is facing an unprecedented crisis. Reasons for this are complex and multifactorial; however, rising rates of burnout will undoubtedly contribute to problems with recruitment and retention. Chronic workplace stress, whereby there are insufficient resources available to meet the demands doctors face, is a contributor to burnout. There are a wide variety of available self-report measures for stress, with heart rate variability (HRV) shown to be a biomarker of stress and recovery in doctors. We aim to triangulate continuous HRV measurements with validated self-report measures and qualitative data to better understand the patterns of stress and recovery.

Methods and analysis
This study has a sequential explanatory mixed-methods design. Participants will be recruited from multiple sites within National Health Service (NHS) Grampian. Initially, participants will complete a suite of validated scales, including the Maslach Burnout Inventory for Medical Personnel, the Resilience Scale for Adults and the Interpersonal, Community, Occupational, Physical, Psychological (ICOPPE) well-being scale. Following this, participants will undertake seven consecutive days of ecological momentary assessment of real-time demands, resources and fatigue, alongside 7 days of continuous ambulatory assessment of HRV via Firstbeat Bodyguard 3 chest-worn monitors. Participants will be provided with a summary report following their study period. If 40 participants are recruited within the recruitment timeframe, multilevel modelling will be used to analyse data; otherwise, N-of-1 statistical techniques will be used. Following initial analysis of the quantitative data, participants of interest will be invited to take part in semistructured interviews, which will be thematically analysed and presented alongside the quantitative data.

Ethics and dissemination
This study was approved by the University of Aberdeen, School of Medicine, Medical Sciences and Nutrition ethics review board (ref. 3389193) and the NHS Grampian research and development team. Results will be disseminated in international peer-reviewed journals.

Trial registration number
NCT06721312.

Background
Mast cell activation is an important driver of abdominal pain in irritable bowel syndrome (IBS). While evidence supports the role of IgE-mediated mast cell activation in visceral pain development in IBS, the role of pseudoallergic MRGPRX2-mediated mast cell activation in this process remains unknown.

Objective
We investigated whether MRGPRX2-mediated mast cell activation plays a role in abdominal pain development in patients with IBS.

Design
MRGPRX2 expression in mast cells and other immune cells was characterised across colon layers using flow cytometry. We evaluated whether MRGPRX2 agonists trigger mast cell degranulation and transient receptor potential vanilloid 1 (TRPV1) sensitisation in healthy human colonic submucosal plexus samples using live imaging. Rectal biopsies were then collected from patients with IBS and healthy volunteers (HV) and MRGPRX2+ mast cell frequency, MRGPRX2 expression per cell, mast cell degranulation kinetics in response to MRGPRX2 agonists, MRGPRX2 agonistic activity and presence of MRGPRX2 agonists in biopsy supernatants were assessed.

Results
MRGPRX2+ mast cells are enriched in the submucosa and muscularis of the healthy human colon. MRGPRX2 agonists induce mast cell degranulation and TRPV1 sensitisation in the healthy colon submucosa. While the frequency of rectal MRGPRX2+ mast cells was unaltered in IBS, submucosal mast cells showed increased degranulation in response to MRGPRX2 agonists in IBS compared with HV. MRGPRX2 agonistic activity was increased in IBS rectal biopsy supernatant compared with HV, which was associated with increased levels of substance P.

Conclusion
The MRGPRX2 pathway is functionally upregulated in the colon of patients with IBS, supporting its role in abdominal pain in IBS.

Introduction
The widespread use of digital devices in modern workplaces has led to a rise in visual health problems, such as myopia and dry eye syndrome, among the working-age population. This study aims to investigate the incidence of eye disorders, associated risk factors and relevant biomarkers in Shenzhen, addressing a crucial gap in the research on visual health in rapidly urbanising Chinese cities.

Methods
This prospective observational cohort study, conducted from September 2024 to December 2029, will recruit 3000 full-time employees aged 18–65 in Shenzhen through multistage sampling across five job sectors. Data collection will include questionnaire surveys, standardised scale assessments, ophthalmic examinations, ophthalmic imaging and biomarker testing. Annual follow-ups will track the incidence of high myopia and dry eye, as well as associated factors and biomarker changes. Data accuracy will be ensured through double entry and continuous quality control.

Ethics and dissemination
The study has been approved by the Ethics Committee of Shenzhen Eye Hospital (2024KYPJ012; 04 February 2024). The results will be presented at professional conferences and submitted for publication in peer-reviewed journals.

Trial registration number
National Health Information Platform (MR-44-24-026548).

Introduction
Immunotherapy has revolutionised cancer treatment. Immune checkpoint inhibitors have demonstrated significant efficacy across multiple tumour types, including gastric cancer, where several approved programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors show promising antitumour activity. While PD-L1 expression serves as a predictive biomarker for PD-1 inhibitor response, and PD-L1-positive patients generally show better outcomes, therapeutic resistance remains a challenge. Many initial responders eventually develop resistance, and surprisingly, some PD-L1-positive patients fail to achieve expected response rates, indicating emerging resistance mechanisms in potentially responsive populations. Adebrelimab, a PD-L1 inhibitor, demonstrates mechanistic advantages over PD-1 inhibitors, with clinical studies suggesting promising therapeutic potential. When combined with irinotecan, apatinib has shown efficacy in second-line gastric cancer treatment. This study aims to evaluate the efficacy and safety of combining adebrelimab with apatinib and irinotecan for advanced gastric cancer refractory to PD-1 inhibitors.

Method and analysis
This single-arm, single-centre exploratory trial will be conducted at Renji Hospital, enrolling 32 patients aged 18–75 years. Eligible patients must have initially achieved partial response, complete response or stable disease with progression-free survival (PFS)≥3 months during prior immunotherapy but subsequently progressive disease on imaging. Treatment will continue until meeting discontinuation criteria. The primary endpoint is objective response rate with Clopper-Pearson 95% CI. Secondary endpoints include disease control rate (95% CI), PFS and overall survival (estimated by Kaplan-Meier method), along with safety assessments.

Ethics and dissemination
All participants will provide informed consent. The protocol has been approved by the Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (LY2023-201-C). The results will be disseminated through peer-reviewed manuscripts, reports and presentations.

Trial registration number
ChiCTR2300077329.

-37%rischio morte con esercizio fisico.Banditi cibi infiammatori

New England Journal of Medicine, Ahead of Print.

This case-control study investigates if a regional homogeneity–magnetic resonance imaging cortical deficit pattern provides a more robust biomarker for major depressive disorder (MDD) than its structural counterpart and informs the underlying, regionally specific lower cerebral blood flow in this disorder.

Con gene di Braf mutato. Combinazione allunga sopravvivenza

La comunicazione alterata tra cellule del cervello chiave nella progressione della malattia

Objectives
Our study was designed to assess whether paired normal-tumour testing increased access to targeted therapy, clinical trials and influenced cancer screening recommendations given to patients and their families.

Design
Prospective cohort study.

Setting
Academic cancer centre in the Pacific Northwest region of the USA.

Participants
Patients newly diagnosed between 01 January 2021 and 31 December 2022 with cancers of the oesophagus, gastro-oesophageal junction and stomach (CEGEJS) were included. All other cancer diagnoses such as head and neck, duodenal and lower gastrointestinal tract cancers were excluded.

Intervention
Paired germline and tumour genetic test within 90 days of new patient visit.

Primary outcome measures
Number of targeted therapies received (or not) when eligible, follow-up treatment data and number of inherited predispositions to cancers identified. No secondary outcome measures.

Results
Of 42 patients, 32 (76.2%) were eligible for at least one targeted therapy. 19 patients received immunotherapy, when 16 had a biomarker predicting immunotherapy benefit, and benefit of immunotherapy was unclear for 3. Another 11 did not have this biomarker, and 6 of them received immunotherapy. Six pathogenic variants were identified in four high-risk genes. By 01 January 2024, 18 patients (42.9%) had died of complications of cancer.

Conclusion
More than 75% of patients who received tumour testing were eligible for a targeted therapy regardless of their stage at diagnosis, emphasising the need to expand access to testing with staging workup to improve survival outcomes. Six families received personalised screening recommendations, thanks to this study.

To the Editor Dr Paterson and colleagues conducted a randomized clinical trial to evaluate the effect of perioperative IV lidocaine on return of gut function after elective minimally invasive colon resection. I was surprised by the lack of discussion regarding the observed difference in postoperative opioid consumption between the lidocaine and placebo groups and its potential impact on the study’s findings.