Search Results for: Le cause della polmonite nei bambini

Objective
Biological age assessed by the Klemera and Doubal method (KDM) and phenotypic age (PhenoAge) was considered as a marker for ageing-related outcomes because it reflects different aspects of biological ageing and health, which are associated with increased risk of death. proBNPage based on N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a novel index for biological age estimation. However, the independence of its relationship with clinical outcomes from established risk factors, KDM or PhenoAge remains uncertain. Their identification could provide valuable information to prognosis.

Design, setting and participants
This study analysed data from the general population included in the National Health and Nutrition Examination Survey (NHANES). Participants who took part in the cross-sectional survey from 1999 to 2004 were included, and all-cause as well as cardiovascular mortality was recorded (up to 31 December 2019).

Outcome measures
All-cause and cardiovascular mortality were considered as outcomes. Clinical risk factors were collected, and biological age was estimated by proBNPage, KDM and PhenoAge. Cox proportional hazards models were used to determine the relationship between proBNPage and outcomes with adjustment for risk factors or other biological age indexes. Restricted cubic spline (RCS) analysis based on multivariate Cox regressions was performed to examine whether there was a non-linear relationship between proBNPage and outcomes.

Results
A total of 9 925 participants were included in this study. The association between proBNPage and outcomes remained significant after adjusting for risk factors, including NT-proBNP (for all-cause mortality, HR 1.14; 95% CI 1.10 to 1.17; for cardiovascular mortality, HR 1.20; 95% CI 1.14 to 1.27). Similar results were obtained after adjusting for KDM plus NT-proBNP (for all-cause mortality, HR 1.31; 95% CI 1.22 to 1.41; for cardiovascular mortality, HR 1.21; 95% CI 1.11 to 1.28) or PhenoAge plus NT-proBNP (for all-cause mortality, HR 1.21; 95% CI 1.16 to 1.28; for cardiovascular mortality, HR 1.35; 95% CI 1.24 to 1.47). These findings were confirmed in most subgroups. A non-linear relationship was observed between proBNPage and all-cause and cardiovascular mortality with an inflection point.

Conclusions
A non-linear positive relationship was observed between proBNPage and clinical outcomes. After adjusting for established risk factors and other biological age estimation indices (KDM or PhenoAge), proBNPage was significantly associated with mortality. The results remain similar after further adjustment for NT-proBNP. These results suggest that proBNPage is a useful surrogate for biological age estimation.

Objectives
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease. Chest high-resolution CT (HRCT) is instrumental in IPF management, and the Quantitative Lung Fibrosis (QLF) score is a computer-assisted metric for quantifying lung disease using HRCT. This study aimed to assess the change in QLF score associated with a minimum clinically important difference (MCID) of IPF symptoms and physiological lung function, and also determine the MCID of QLF change associated with all-cause mortality to serve as an imaging biomarker to confirm disease progression and response to therapy.

Design and study setting
We conducted post hoc analyses of prospective data from two IPF phase II studies of pamrevlumab, a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity.

Participants
Overall, 152 patients with follow-up visits after week 24.

Methods
We used the anchor-based Jaeschke’s method to estimate the MCID of the QLF score that corresponded with the already established MCID of St. George’s Respiratory Questionnaire (SGRQ) and percent-predicted forced vital capacity (ppFVC). We also conducted a Cox regression analysis to establish a sensitive and robust MCID of the QLF score in predicting all-cause mortality.

Results
QLF changes of 4.4% and 3.6% corresponded to the established MCID of a 5-point increase in SGRQ and a 3.4% reduction in ppFVC, respectively. QLF changes of 1% (HR=4.98, p=0.05), 2% (HR=4.04, p=0.041), 20 mL (HR=6.37, p=0.024) and 22 mL (HR=6.38, p=0.024) predicted mortality.

Conclusion
A conservative metric of 2% can be used as the MCID of QLF for predicting all-cause mortality. This may be considered in IPF trials in which the degree of structural fibrosis assessed via HRCT is an endpoint. The MCID of SGRQ and FVC corresponds with a greater amount of QLF and may reflect that a greater amount of change in fibrosis is required before there is functional change.

Trial registration number
NCT01262001, NCT01890265.

Stroke, Ahead of Print. BACKGROUND:The most common cause of arterial ischemic stroke in healthy children, focal cerebral arteriopathy (FCA), can progress rapidly over days with worsening brain injury. A 2017 retrospective Swiss study of corticosteroid treatment for FCA changed practice. To assess its impact, we compared the FCA cohorts from the 2 VIPS (Vascular Effects of Infection in Pediatric Stroke) prospective cohort studies.METHODS:The VIPS II study prospectively enrolled 205 children (29 days to 18 years) with arterial ischemic stroke at 22 centers, December 2016 to January 2022. The local team measured 12-month outcomes using the pediatric stroke outcome measure. A neuroradiologist and pediatric vascular neurologist independently reviewed all clinically obtained imaging and clinical data to classify the cause of arterial ischemic stroke. The neuroradiologist measured the FCA Severity Score on vascular imaging performed at any time poststroke. We compared the VIPS II FCA cohort to the previously published FCA cohort from VIPS I (2010–2014; 37 centers).RESULTS:Of 75 children with definite arteriopathy enrolled in VIPS II, 32 (43%) had FCA, compared with 41 of 127 (32%) of definite arteriopathy cases in VIPS I. The median age was 11.3 years (56% male) in VIPS I and 11.4 years (55%) in VIPS II. Treatment with intravenous corticosteroids increased from 2 of 41 (5%) of FCA patients in VIPS I to 18 of 32 (56%) in VIPS II. The VIPS II FCA cases were more severe at baseline (median FCA Severity Score 6 versus 4;P=0.006). There were no significant differences in either the change in FCA Severity Score (baseline to maximum) or the 12-month neurological outcomes.CONCLUSIONS:Treatment of FCA with corticosteroids increased dramatically between the VIPS I and VIPS II studies. VIPS II cases were more severe at baseline, but we observed no significant difference in disease progression or neurological outcomes. Given the low level of evidence supporting corticosteroid therapy, pediatric stroke centers should enroll FCA patients into ongoing FCA corticosteroid treatment trials.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifiers: NCT04873583 and NCT06040255.

Stroke, Ahead of Print. BACKGROUND:Carotid web is a rare and likely underrecognized cause of ischemic stroke, particularly in young patients. Given the high risk of recurrence, diagnostic delays may have serious consequences. This study aimed to assess the incidence and impact of delayed carotid web diagnosis after a first ischemic event.METHODS:We conducted a retrospective analysis using data from the French ongoing multicenter prospective CAROWEB (Carotid Web registry). We included patients with a first-ever ischemic stroke or transient ischemic attack in the anterior circulation, attributed to an ipsilateral carotid web with no other identifiable cause, between September 2013 and April 2023. Patients with missing data on the date of the first ischemic event or carotid web diagnosis, or with prior stroke history, were excluded. Participants were categorized into early diagnosis (≤30 days) and delayed diagnosis ( >30 days) groups. Factors associated with diagnostic delay were investigated through univariable and multivariable analyses. Stroke recurrence was evaluated using Kaplan-Meier survival analysis.RESULTS:Of 280 patients in the registry, 225 met the inclusion criteria. A delayed diagnosis occurred in 57 patients (25.3%). Independent predictors of diagnostic delay included lower initial National Institutes of Health Stroke Scale score (odds ratio, 0.92;P=0.002), stroke occurring before 2019 (odds ratio, 0.19;P

Introduction
Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard first-line treatment for atonic PPH. The PPH rate is increasing, and this may be partially related to the overuse of oxytocics in labour. Laboratory studies on myometrium suggest that repeated use of oxytocics leads to the saturation of oxytocin receptors and reduced therapeutic efficacy of oxytocin. Carboprost (a prostaglandin analogue) is usually reserved for second-line management of atonic PPH. A systematic review comparing the efficacy of carboprost and conventional uterotonics for PPH prophylaxis found that carboprost was associated with less blood loss, but around 15% of women experienced side effects. The study’s aim is to compare intramuscular carboprost with intravenous oxytocin for the initial treatment of PPH. In addition, to assess the cost-effectiveness of both treatments, participants’ views on the two treatments and the consent process.

Methods and analysis
COPE is a double-blind, double-dummy, randomised controlled trial that aims to recruit 2000 women (1:1 allocation, stratified by mode of birth) across 20 hospitals in the UK. Due to the emergency nature of PPH, COPE uses a research without prior consent (RWPC) model. Randomisation and treatment will occur if eligibility criteria are met once bleeding starts. Postnatal consent will be sought for disclosure of identifiable data and continued follow-up. Clinical efficacy outcomes will be collected at 24 and 48 hours or at hospital discharge, if sooner. Questionnaires will also be collected at 24 hours and 4 weeks postrandomisation. Cost-effectiveness will be based on the incremental cost per quality-adjusted life-year, calculated from the perspective of the NHS and personal social services.

Ethics and dissemination
This study has been approved by the Coventry and Warwickshire Research Ethics Committee (REC) (18/WM/0227) and the Health Research Authority. Results will be disseminated via peer-reviewed publications.

Trial registration number
ISRCTN16416766.

Objectives
This study aims to investigate the relationship between the triglyceride-glucose (TyG) index in patients with early sepsis-associated acute kidney injury (SA-AKI) and the risk of in-hospital mortality.

Design
Secondary data analysis.

Setting
This study analysed secondary data from the Medical Information Mart for Intensive Care (MIMIC) 2008–2022.

Participants
A total of 1632 participants were enrolled in the final analysis.

Primary and secondary outcome measures
A secondary data analysis study was conducted using data from the MIMIC IV 3.0 database. Participants were divided into four groups based on the quartiles of the TyG index. The primary outcome was all-cause in-hospital mortality. The association between the TyG index and in-hospital mortality among SA-AKI patients was assessed using multivariate COX proportional hazards regression analysis and restricted cubic spline regression analysis. Subgroup and sensitivity analyses were performed to verify the robustness of results.

Results
A total of 1632 patients were included in the study. The in-hospital mortality rate was 31.13%, and the intensive care unit (ICU) mortality rate was 25.25%. Multivariate COX regression analysis showed that the TyG index was independently associated with an increased risk of in-hospital mortality (HR 1.14 (95% CI 1.02 to 1.27); p=0.02) and ICU mortality (HR 1.17; (95% CI 1.04 to 1.32); p=0.01). The restricted cubic spline regression model indicated that the risk of in-hospital and ICU mortality increased linearly with the increase in the TyG index. Sensitivity analysis demonstrated that the effect size and direction were consistent across different subgroups, and the results were stable.

Conclusion
A high TyG index is associated with increased mortality during hospitalisation in patients with SA-AKI. Larger-scale prospective studies are needed to confirm these findings.

Introduction
Acute pneumonia (AP) remains a leading cause of death in the older population. Excess risk of death after AP is partly due to cardiovascular (CV) events. We aim to evaluate whether aspirin at a preventive dose (100 mg daily) introduced at the acute phase of AP reduces 90-day mortality.

Methods and analysis
The ASPirin for Acute Pneumonia in the elderlY study is a phase III multicentre randomised double-blind, placebo-controlled, superiority clinical trial, which will investigate the efficacy and safety of aspirin in older patients with AP hospitalised in a French university and non-university hospitals. Patients will be randomised in a 1:1 ratio between two groups receiving daily either 100 mg of aspirin or a placebo, within 84 hours following radiologically proven AP diagnosis for 90 days. This study aimed at assessing the efficacy of aspirin on all-cause mortality after AP at 90 days (D90) (primary objective), D30 and D120 after randomisation, CV mortality, major adverse CV events (MACE) (ie, myocardial infarction, stroke, heart failure, new atrial fibrillation and pulmonary embolism, CV death and sudden death) incidence, length of intensive care unit and hospital stay, unscheduled rehospitalisation, dependence, overall and MACE-free survival, as well as safety outcomes (bleeding incidence). The sample size, calculated considering a 90-day mortality of 25% and a reduction of 10% in the aspirin group, a two-sided alpha risk at 5% and power of 80%, is 500 patients to prove the superiority of aspirin over placebo. To account for screening failures and consent withdrawals, 600 patients (300 per arm) will be included.

Ethics and dissemination
This study has full approval from an independent Ethics Committee. Participants will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.

Trial registration number
EU CTIS: 2024-510811-32-00.

Dopo svariati arresti cardiaci. Mistero sulle cause del decesso

Background
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The combination of tremelimumab and durvalumab is now a standard treatment option for advanced HCC.

Objective
To study immune responses in HCC patients treated with tremelimumab and durvalumab.

Design
We treated 28 HCC patients with durvalumab, tremelimumab and locoregional therapies. We performed a high-dimensional multiomics analysis including whole exome sequencing, single-cell RNA seq, CO-Detection by indEXing, flow cytometry and multiplex cytokine/chemokine analysis of patients’ blood and tumour samples and integrated this data to elucidate immune correlatives and response mechanisms. Mice with syngeneic HCC were treated with anti-PD-L1 plus anti-CTLA4 for hepatic lymphocytes, tumour-infiltrating lymphocytes and peripheral blood mononuclear cell analysis.

Results
The median overall survival was 19.2 months. Tumour tissue analysis revealed enhanced interferon responses, with stronger effects in responders. Gene set variation analysis indicated enhanced antigen presentation in responders. Spatial analysis revealed that non-responder tumours had higher numbers of Tregs located in neighbourhoods enriched with immune cells and expressed higher levels of ICOS and PD-1. Conversely, non-responder PD1+CD8+T in these Treg-enriched neighbourhoods expressed lower ICOS. Cell-communication analysis demonstrated that Treg-CD8+T interaction was enhanced in non-responder tissue. Peripheral blood analysis showed increased classical monocytes in responders and Tregs in non-responders. Treg-CD8+T interaction was confirmed in preclinical models. Finally, single-patient computational analysis from the all-across analysis was performed on 860 features, which led to the identification of multiomics feature sets including Treg features.

Conclusion
Our study provides a blueprint for in-depth analysis of immune correlates in immunotherapy studies and demonstrates the importance of Treg distribution in HCC.

Trial registration numbers
NCT02821754 and the EudraCT identifier: 2019-002767-98.

Case presentation A 71-year-old man presented with a 2-months history of arrhythmia of undetermined cause, dysphagia, vomiting and 10 kg weight loss. The patient’s history was unremarkable except for multinodular goitre and hypertension. Laboratory exams did not demonstrate significant alterations, white cell count was 7.8×109/L (ref range: 4.0–10.0), haemoglobin 16.2 g/L (ref range: 12.0–15.0), platelet 281×109/L (ref range: 150–450), C reactive protein

Background
Oat ingestion in coeliac disease (CD) is generally regarded as safe but can trigger enteropathy and T cells specific for oat avenin in the gut and blood of some individuals.

Objective
To correlate immune and clinical outcomes to oats, purified avenin and oat feeding studies were performed to examine symptoms, T-cell immunity and intestinal histology in CD.

Design
33 treated HLA-DQ2.5+ adult CD patients underwent single-bolus or 6-week oat avenin or 3-month whole oats ingestion. T cell activation after avenin ingestion was measured using serum interleukin 2 (IL-2), a sensitive and specific biomarker of gluten-induced T cell activation and symptoms in CD. Symptom measures, intestinal histology, and immune studies on blood and duodenum were undertaken.

Results
Among 29 CD participants, avenin induced dose-dependent T-cell activation in 11 (38%) and acute symptoms in 17 (59%). Higher IL-2 levels correlated with more severe symptoms. A single highly symptomatic patient vomited in response to avenin (1/29; 3%) and exhibited a striking pro-inflammatory cytokine profile similar to wheat-induced responses. Avenin increased the frequency of CD38-expressing tetramer+integrin β7+ T effector memory CD4+ T cells in the blood, however symptoms, IL-2 release and tetramer frequency fell following 6-week avenin intake and no enteropathy was observed.

Conclusion
Gluten-contamination-free oats can trigger acute dose-dependent immune and symptom responses but usually at a level insufficient to cause sustained symptoms or enteropathy. In 1 of 29 (3%) participants, oat avenin triggered a pro-inflammatory wheat-like response, highlighting that a minority of CD patients may need to exclude oats. Informed choice regarding oats ingestion in CD is important.

Background
Cyst size, its growth rate, and diameter of the main pancreatic duct (MPD) are all associated with pancreatic carcinoma prevalence in intraductal papillary mucinous neoplasms (IPMNs).

Objective
To examine the above factors in relation to future risk of incident pancreatic carcinoma in individuals with IPMNs harbouring no high-risk stigmata.

Design
In a prospective longitudinal cohort, we analysed 2549 patients with IPMNs. A multivariable cause-specific Cox proportional hazards regression model was built to estimate HRs for incident pancreatic carcinoma.

Results
IPMN size at baseline and its annual growth rate over 2 years of follow-up were associated with incident pancreatic carcinoma (ptrend

Objectives
To develop and validate a risk prediction model for adverse outcomes in patients with angina with non-obstructive coronary arteries (ANOCA) confirmed by invasive coronary angiography.

Design
Retrospective cohort study.

Setting
A tertiary cardiovascular care centre in China.

Participants
From 17 816 consecutive patients undergoing coronary angiography for suspected coronary artery disease, 5934 met ANOCA criteria after rigorous exclusion: (1) significant stenosis (≥50% luminal narrowing), (2) established coronary artery disease history, (3) incomplete baseline/follow-up data, (4) non-cardiovascular life-limiting conditions.

Primary and secondary outcome measures
The primary outcome was a composite of all-cause death, non-fatal myocardial infarction (MI), stroke and repeat percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The secondary outcome was major adverse cardiovascular events, defined as cardiac-related death, non-fatal MI, non-fatal stroke, repeat PCI and CABG.

Results
The derivation cohort (n=4452) and validation cohort (n=1482) demonstrated comparable baseline characteristics. The nomogram incorporated eight prognosticators: age, haemoglobin, serum urea, serum sodium, alanine aminotransferase/aspartate aminotransferase ratio, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left atrial diameter and left ventricular ejection fraction. The prediction model showed robust discrimination for primary endpoint, achieving area under the curve (AUC) values of 0.82 (1 year), 0.90 (2 years) and 0.89 (3 years) in the derivation cohort, with corresponding validation cohort AUCs of 0.75, 0.77 and 0.78. Calibration plots revealed close alignment between predicted and actual event-free survival probabilities in both cohorts. Risk stratification identified two distinct prognostic groups with significant survival differences (log-rank p

Introduction
Patients with chronic limb-threatening ischaemia (CLTI) are often prescribed clopidogrel in order to reduce their risk of major adverse limb and cardiovascular events. Clopidogrel is metabolised by the CYP2C19 enzyme and genetic variations in CYP2C19 are common. These variants can influence an individual’s ability to metabolise clopidogrel to its active metabolite. Few studies have investigated the relationship between patient genotype and outcomes in vascular surgery. This work aims to establish the relationship between patient genotype and outcomes after revascularisation in patients with CLTI who are prescribed clopidogrel. It will consider whether pharmacogenetics can be used to ensure patients are prescribed effective medications to optimise their outcomes.

Methods and analysis
This is an observational cohort study of patients undergoing lower limb surgical, endovascular or hybrid revascularisation for CLTI at Manchester University NHS Foundation Trust. Patients taking clopidogrel post-procedure, as well as those prescribed a non-clopidogrel based medication regimen, will be recruited prior to or shortly after revascularisation. Patients will undergo CYP2C19 genotyping and will be followed up using online records. The study has 90% power to detect 114 amputations with a target sample size of 483 participants. The primary outcomes are risk of amputation at 1 year and a composite endpoint for the risk of major adverse limb events (MALE) or death from any cause at 1 year. Secondary outcomes are risk of MALE at 1 year, risk of major adverse cardiovascular events (MACE) or death from any cause at 1 year, death within 30 days of revascularisation, minor re-interventions at 1 year, total number of re-interventions at 1 year and rate of systemic or gastrointestinal bleed at 1 year.
Risk of amputation, MALE and MACE will be analysed using Cox models. All remaining outcomes will be analysed using negative binomial models. Potential competing events for the risk of amputation will be investigated as part of a sensitivity analysis. Patients given a non-clopidogrel-based medication will be compared as an additional analysis.

Ethics and dissemination
Manchester University Research Ethics Committee approval obtained as part of the Implementing Pharmacogenetics to Improve Prescribing (IPTIP) trial process (IRAS 305751). The results of the study will be published in a peer-reviewed journal and presented at international conferences.

Registration
This work is a sub-protocol for the IPTIP study which is registered as ISRCTN14050335.

Objectives
To compare the incidence and drivers of major adverse kidney events (MAKEs) between COVID-19 and non-COVID-19 acute respiratory distress syndrome (ARDS) patients, with a focus on long-term kidney outcomes.

Design
Retrospective cohort study.

Setting
Single-centre intensive care unit in the Midlands, UK.

Participants
708 ARDS patients (458 COVID-19, 250 non-COVID-19).

Primary and secondary outcome measures
The primary outcome was MAKE at 365 days (MAKE-365), defined as new renal replacement therapy (RRT), estimated glomerular filtration rate (eGFR)