Search Results for: Scoperte le cause biologiche della depressione

Analisi di Women in Rare per capire cause e impatto del ritardo

Analisi di Women in Rare per capire cause e impatto del ritardo

Può essere paragonata al laser, utilizzabile per varie patologie. In questo caso, si può applicare nel campo della neurologia, per curare cefalee ed emicranie. In quello della psichiatria, per trattare…

Circulation, Ahead of Print. BACKGROUND:Hereditary hemorrhagic telangiectasia is an inherited vascular disorder characterized by arteriovenous malformations (AVMs). Loss-of-function variations in activin receptor-like kinase 1 (ALK1) cause type 2 hereditary hemorrhagic telangiectasia, andAlk1knockout mice develop AVMs, along with overactivation of vascular endothelial growth factor receptor 2/phosphoinositide 3-kinase/AKT signaling. The full spectrum of signaling alterations resulting fromALK1variations remains unknown, and more effective and specific inhibitors to combat AVM formation in patients are needed.METHODS:Single-cell RNA sequencing of endothelial-specificAlk1knockout mouse retinas and controls was performed. Overexpression of fluid shear stress signaling signatures including the mechanosensitive ion channel PIEZO1 was confirmed in mouse and human type 2 hereditary hemorrhagic telangiectasia lesions. Genetic and pharmacological PIEZO1 inhibition was tested inAlk1knockout mice, along with downstream PIEZO1 signaling.RESULTS:A cluster ofAlk1mutant endothelial cells with altered arterio-venous identity overexpressed pathways related to fluid shear stress, hypoxia, inflammation, cell cycle, and vascular endothelial growth factor receptor 2/phosphoinositide 3-kinase/AKT signaling.Piezo1deletion and pharmacological inhibition inAlk1-deficient mice mitigated AVM formation, whereasPiezo1overexpression enhanced AVM formation induced by ALK1 ligand blockade. Mechanistically, PIEZO1 inhibition reduced elevated vascular endothelial growth factor receptor 2/AKT, ERK5-p62-KLF4, endothelial nitric oxide synthase, hypoxia, proliferation, and inflammation in ALK1-deficient endothelium.CONCLUSIONS:PIEZO1 expression and signaling are elevated in type 2 hereditary hemorrhagic telangiectasia. PIEZO1 blockade reduces AVM formation and alleviates cellular and molecular hallmarks of ALK1-deficient cells. This finding provides new insights into the mechanistic underpinnings of ALK1-related vascular diseases and identifies potential therapeutic targets to prevent AVMs.

I pazienti con BPCO e diabete di tipo 2 presentano un rischio ridotto di ricovero per BPCO, di necessità di ricorrere alla ventilazione non invasiva a pressione positiva e di mortalità per tutte le cause se assumono un inibitore del co-trasportatore sodio-glucosio 2 (SGLT2i). Queste le conclusioni di uno studio retrospettivo, condotto a Taiwan, i cui risultati sono stati pubblicati negli Annals of the American Thoracic Society.

The American Heart Association’s PREVENT calculator, released in 2023, estimates 10-year and 30-year risks of cardiovascular events. In addition to predicting myocardial infarction, or heart attack, and stroke, a new study in the Journal of the American Heart Association found that the 10-year estimates accurately predicted subclinical atherosclerosis, a condition in which plaques are present but don’t cause symptoms or signs of disease.

Circulation, Ahead of Print. BACKGROUND:The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.METHODS:We calculated the American Heart Association’s Life’s Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life’s Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life’s Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular disease–specific mortality, and all-cause mortality.RESULTS:We identified 609 cytosine-phosphate-guanines (CpGs) associated with Life’s Essential 8 score at false discovery rate

Introduction
Community-acquired pneumonia is the leading global cause of infection-related death. A subset of patients with pneumonia develops aberrant immune responses, resulting in harmful inflammation, tissue damage and significant mortality. Immunomodulatory therapies aim to blunt this dysregulated immune response and reduce resultant injury. No consensus exists on the use or impacts of immunomodulatory therapies in the management of community-acquired pneumonia. This protocol describes the methods we will use to undertake a systematic review and network meta-analysis of the effects of immunomodulatory therapies on the mortality of patients with community-acquired pneumonia.

Methods
We will undertake a systematic review and network meta-analysis investigating the use of immunomodulatory therapies in community-acquired pneumonia. Our protocol has been developed and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines and prospectively registered with PROSPERO (CRD42024565301). The primary objectives of this work are to compare the impact of immunomodulatory therapies on 28-day and 90-day mortality in adult patients admitted to hospital with a primary diagnosis of community-acquired pneumonia. The secondary objectives of this work are to identify any differences in the effectiveness of these immunomodulatory therapies in managing community-acquired pneumonia of differing aetiology and severity.
We will conduct a literature search of Medline, Embase, Scopus, Web of Science and Global Health for all relevant articles until 30 June 2024. All observational, interventional and epidemiological studies published in English will be included, and each type of study design will be examined separately. All studies will have their titles and abstracts independently screened by two reviewers, followed by a full article eligibility review and data extraction. A third reviewer will adjudicate any disagreements. Data extracted will include, but not be limited to, the study design, country in which it was undertaken, patient characteristics (eg, age, sex, cause of CAP, severity of CAP), details regarding the immunomodulatory therapy and dosing used and the 28-day and 90-day mortality of each study arm.

Analysis
The risk of bias will be assessed using the Risk of Bias in Non-randomised Studies – of Exposure tool for non-randomised studies and the Cochrane Risk of Bias 2 tool for randomised control trials. The quality of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations for network meta-analysis framework. A quantitative synthesis of data is planned for 28-day and 90-day mortality rates.
We will fit a random-effects network meta-analysis model that includes random effects for between-study heterogeneity and for inconsistency. This will be done using the metafor package for R. We will use a contrast-based approach, modelling estimated treatment effects using reference treatments. In the case of the primary objective, this will be the log odds ratio (OR) of mortality in one treatment compared with another.
Each type of study design will be examined separately. Treatments using the same immunotherapy at different doses may be grouped if appropriate.

Ethical approval and dissemination
This will be a systematic review of published literature; therefore, ethical approval is not required. To ensure communication of our findings, we will publish our results in a peer-reviewed journal and present our findings at appropriate local, national and international meetings.

PROSPERO registration number
CRD42024565301.

Background
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality worldwide. Despite the organised CRC screening programme, the uptake rate of the population-based CRC screening was still low. Thus, we will conduct a randomised controlled trial in a community setting to evaluate the effectiveness of a theory-based chatbot in promoting CRC screening uptake.

Methods and analysis
A total of 500 eligible participants will be randomly assigned to a WhatsApp Messenger-initiated chatbot outreach group or a standard text reminder group at a ratio of 1:1. The intervention group will deliver Chinese culturally tailored education texts and videos developed based on the Health Belief Model and the Trans-Theoretical Model. The control group will deliver a standard text reminder of information about the Hong Kong organised CRC screening programme. In addition to the baseline assessment and postintervention assessment, all subjects will be followed up for 3 months and 6 months, respectively. The primary outcome will be the CRC screening uptake rate at the 3 month and 6 month follow-up. The secondary outcomes will be the intention to undergo CRC screening uptake, time interval to participate in and complete screening after recruitment, and reasons for not participating in screening at the 3 month and 6 month follow-up. Quantitative data will be analysed using Student’s t-test, Pearson’s 2 test or Fisher’s exact test. Qualitative data will be analysed by thematic analysis.

Ethics and dissemination
Ethical approval of this trial was granted by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (2022.614). Written informed consent will be obtained from study participants before enrolment. The findings will be disseminated through peer-reviewed journals.

Trial registration number
The study was registered on clinicaltrials.gov (NCT06192862).

Circulation, Ahead of Print. BACKGROUND:Abdominal aortic aneurysms (AAA) present with high morbidity and mortality when they occasionally rupture. No medical therapy has successfully been proven to reduce AAA growth, though both metformin and statins have been identified as potential treatments in multiple meta-analysis. This study aimed to investigate a potential relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death.METHODS:The study population included all men with screening-detected AAAs (30–55 mm) from the 2 large, population-based, randomized screening trials; the Viborg Vascular Screening trial (inclusion, 2008–2011) and the Danish Cardiovascular Screening trial (inclusion, 2014–2018). The clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. Statin exposure was quantified by defined daily doses (DDD). The primary outcome was AAA growth rate, whereas secondary outcomes included the need for repair and a composite of repair, rupture, and all-cause death. Growth rates were calculated using linear regression. To evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, 5-year follow-up, or December 31, 2021.RESULTS:A total of 998 aneurysmal men (median age, 69.5 [interquartile range (IQR), 67–72] years; median AAA diameter, 35.4 [IQR, 32–41.2] mm) were included. Statin use was significantly associated with reduced AAA growth rate; an increase of 1 DDD statin per day was associated with an adjusted change in growth rate of −0.22 mm/year [95% CI, −0.39 to −0.06];P=0.009). The 5-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a significantly reduced adjusted hazard ratio (HR) of 0.82 ([95% CI, 0.70–0.97];P=0.023), which was significant after 2.5 years. Statin use was associated with a significantly lower risk of the composite outcome (surgery, rupture, and death) in a dose-dependent manner, with an adjusted HR of 0.83 ([95% CI, 0.73–0.94];P=0.003) per doubling of statin dose. Findings were robust in a variety of sensitivity analyses.CONCLUSIONS:High-dose statin use was associated with decreased AAA growth rates and lowered risk of undergoing repair, rupture, and death. This nonrandomized study suggests that patients with AAA could benefit from high-dose statin use, beyond only targeting associated risk factors.

Introduction
Distal radius fractures account for one-fifth of all fractures in the active elderly population and may cause chronic pain, loss of hand function and reduced work productivity, imposing a significant socioeconomic burden. Most are initially treated with closed reduction and casting, but 30% subsequently require surgery due to insufficient realignment. The current approaches for analgesia for closed reduction are suboptimal. A brachial plexus nerve block provides complete pain relief and muscle relaxation distal to the elbow, potentially creating better conditions for realignment of the fractured bone ends. This may ultimately translate into reduced need for surgery and result in better functional outcomes and fewer complications compared to a haematoma block, which is the current standard care in Denmark.

Methods and analysis
The BLOCK Trial is an investigator-initiated, parallel-group, allocation-concealed, outcome assessor and analyst-blinded, superiority, randomised, controlled, clinical multicentre trial performed at 11 Danish emergency departments. Eligible adult patients with a distal radius fracture who need closed reduction will be included and allocated 1:1 to either an ultrasound-guided brachial plexus nerve block or a haematoma block. The primary outcome is the proportion of patients with distal radius fracture surgery 90 days after closed reduction. We will include 1716 participants to detect or discard a relative risk reduction of surgery of 20%. Secondary outcomes include treatment-related complications, patient-reported wrist function, pain during closed reduction and proportion of patients with unacceptable radiographic fracture position immediately after closed reduction.

Ethics and disseminationf
The trial is approved by the Danish Medicines Agency and the Danish Research Ethics Committees (EU CT number: 2024-512191-35-00). All results will be summarised on www.theblocktrial.com, clinicaltrials.gov and euclinicaltrials.eu after publication. Primary and secondary outcome results from 0 to 90 days will be presented in the main article and submitted to a peer-reviewed journal. Results from outcomes on the 12-month follow-up will be presented separately.

Trial registration number
NCT06678438.

Annals of Internal Medicine, Ahead of Print.

Objectives
To investigate the association between triglyceride-glucose (TyG) index levels at hospital admission and the risk of in-hospital adverse events, including all-cause mortality, in patients with acute myocardial infarction (AMI). The primary hypothesis was that higher TyG index levels are associated with greater risk of adverse in-hospital outcomes.

Design
Retrospective cohort study.

Setting
Tertiary hospital inpatient care in China. The study included consecutively hospitalised patients with AMI between 1 August 2011 and 10 January 2022.

Participants
A total of 3458 patients with AMI were included. The mean age was 60.8 years, and 78.4% were men. Patients were excluded if they had incomplete data for TyG index calculation or outcome ascertainment.

Interventions
No therapeutic intervention was assigned; the study was observational. TyG index was calculated using fasting triglycerides and fasting plasma glucose levels at admission.

Primary and secondary outcome measures
The primary outcome was all-cause in-hospital mortality. Secondary outcomes included cardiogenic shock and fatal rapid arrhythmia. Outcomes were identified through standardised clinical records.

Results
Among 3458 patients, 375 (10.84%) died during hospitalisation, 236 (6.84%) developed cardiogenic shock and 147 (4.25%) experienced fatal rapid arrhythmia. After multivariable adjustment, higher TyG index levels were significantly associated with increased odds of all-cause mortality (OR, 1.27; 95% CI, 1.02 to 1.57; p

The monoclonal antibody nirsevimab demonstrated strong real-world protection against respiratory syncytial virus (RSV)—the leading cause of infant hospitalization in the US—in a meta-analysis published in The Lancet Child & Adolescent Health.

To the Editor The TRAUMOX2 trial compared restrictive and liberal oxygen delivery in adult trauma patients. Hyperoxia-induced reactive oxygen species formation has been shown to cause a myriad of complications, including pulmonary toxicity. Even though the liberal oxygen group had a lower rate of hypoxemic episodes (3.8% vs 6%), they experienced a higher incidence of atelectasis as an adverse event compared with the restrictive oxygen group (34.7% vs 27.6%) (eTable 9 in the article’s Supplement 2). Here, we offer plausible explanations for the findings.

Clinical presentation A 26-year-old man was diagnosed with a 4-month history of ulcerative colitis. At the time of diagnosis, an abdominal CT showed a thickened colorectum (figure 1A) and a normal liver (figure 1B). He was started on mesalazine 4 g/day and received this for approximately 2 months without therapeutic benefit. He clinically deteriorated and was admitted to the hospital with a fever of up to 38.5°C daily, abdominal pain and diarrhoea. Laboratory findings revealed significantly elevated white blood cells (13.86×109/L), C reactive protein (69.5 mg/L) and elevated liver enzymes: aspartate aminotransferase 245 U/L, alanine aminotransferase 368 U/L (normal