Risultati per: Nuovi farmaci per il danno renale acuto (Acute kidney injury – AKI)

To the Editor We read with interest the SIRAKI02 trial by Dr Pérez-Fernández and colleagues, which was recently published in JAMA. They report a reduction in acute kidney injury (AKI) when using an extracorporeal blood purification (EBP) device during nonemergent cardiac surgery that required cardiopulmonary bypass. The purification column used in this study was proposed to reduce AKI risk via removal of intraoperative inflammatory cytokines and damage-associated molecular patterns, such as free hemoglobin. The reduction of inflammatory cytokines was supported by a reported reduction in circulating tumor necrosis factor α and interleukin 8 in the EBP group compared with the control group.

This cross-sectional study explores whether hospital participation in the Acute Hospital Care at Home program continued to increase following the extension of the program and the characteristics of participating hospitals.

In patients managed with an early invasive approach, P2Y12 inhibitor pretreatment was not associated with reduced ischemic events or increased major bleeding.

Objective
This study aimed to investigate the incidence of overweight in patients with major depressive disorder (MDD) comorbid anxiety during the acute phase and to explore associated factors.

Design
Cross-sectional study.

Setting
Wuhan Mental Health Center, China, from July 2017 to August 2022.

Participants
737 hospitalised patients diagnosed with MDD in the acute phase with comorbid anxiety symptoms.

Primary outcome measures
Incidence and clinical correlations of overweight (body mass index (BMI) ≥ 24).

Results
Among the study population, 55.63% were classified as overweight. Binary logistic regression analysis revealed that being married (B=0.28, p value=0.018, OR=1.10), thyroid-stimulating hormone (TSH) levels (B=0.10, p value=0.001, OR=1.10) and low-density lipoprotein cholesterol (LDL-C) levels (B=1.61, p value=0.045, OR=1.18) were significant positive predictors of overweight. Additionally, multiple linear regression indicated that TSH levels (B=0.16, t=3.17, p value=0.002) were positively associated with higher BMI values.

Conclusion
Over half of the hospitalised MDD patients with comorbid anxiety are overweight. Thyroid function emerges as a crucial clinical factor for overweight in this population. Targeted interventions focusing on thyroid function may be a promising approach for managing overweight in these patients.

New England Journal of Medicine, Ahead of Print.

Diabetic patients with eGFRs

Introduction
Acute pain levels following orthopaedic injury (eg, fracture) are a predictor of the onset of chronic pain, which affects nearly 50% of fracture patients and impairs functional recovery. Among current pharmacological treatments for acute pain, non-steroidal anti-inflammatory drugs have been associated with delayed bone healing, while opioids inhibit effective bone remodelling, increase the risk of pseudarthrosis and carry a high risk of addiction. In light of this, the development of new pain treatments is essential. Cannabidiol (CBD), a non-addictive and non-psychotropic cannabis component stands out as a potential therapeutic agent, given its analgesic and anti-inflammatory properties as well as its potential benefits for bone healing. This randomised controlled trial aims to investigate the effect of acute CBD treatment, compared with placebo, on patients’ self-reported pain, inflammation and well-being following a fracture injury.

Methods and analysis
This is a triple-blind, randomised, placebo-controlled clinical trial. A total of 225 adults aged 18–70 years, who have suffered a long bone fracture and were treated at the Hôpital du Sacré-Coeur de Montréal, will be randomly assigned within 1 week to one of three treatment arms (25 mg or 50 mg of CBD or placebo) for 1 month. The primary outcome will be the difference in the pain score between groups at 1-month follow-up. Secondary outcomes will include measures of persistent pain, inflammation, opioid usage, quality of life, sleep quality, depression, anxiety, cognition and orthopaedic function. Data will be collected at baseline, 1-month and 3-month follow-ups.

Ethics and dissemination
This study obtained a Health Canada licence for use of cannabis products. It has also been approved by Health Canada and the Research Ethics Board of the CIUSSS du Nord-de-l’Île-de-Montréal (Project ID 2025-2105). The findings will be published in a peer-reviewed journal and presented at local, national and international conferences. The trial’s results will be made publicly available on the ClinicalTrials.gov database.

Trial registration number
NCT06448923.

Background
Statins are considered a promising therapy in traumatic brain injury (TBI) because of their role in mediating inflammatory injury and other endothelial properties. Whether they can improve patient outcomes is unknown.

Objectives
To evaluate the effect of statins in critically ill patients with TBI.

Design
Systematic review and meta-analysis of randomised controlled trials.

Eligibility criteria
Trials of adult patients with acute moderate or severe TBI.

Methods
We searched Medline, Embase, Cochrane Central and Web of Science databases for trials comparing the use of any statin with placebo or other interventions. Our primary outcome was the Glasgow Outcome Scale (GOS or GOS extended); secondary outcomes were mortality, intensive care unit (ICU) and hospital length of stay. We used inverse variance random-effects models to calculate risk ratios (RR) and weighted mean differences. We assessed the risk of bias of trials using the Cochrane risk of bias assessment tool and the presence of statistical heterogeneity using the I2 index. Levels of evidence for summary effect measures were evaluated using Grading of Recommendations Assessment, Development and Evaluation methodology.1

Results
Of the 2418 retrieved records, 7 trials met our eligibility criteria. Three studied simvastatin, and four studied atorvastatin. The duration of the intervention ranged from 2 to 10 days, and outcomes were assessed between ICU discharge and 6 months. Five trials were considered at high risk of bias. We observed no statistically significant association between statins and the GOS (RR 0.42; 95% CI, 0.14 to 1.22; two trials; n=84, I2=0%; very low certainty) or mortality (RR 0.59; 95% CI, 0.25 to 1.44; three trials; n=160, I2=0%; very low certainty). No significant effect was observed for ICU length of stay, while hospital length of stay was evaluated in one trial showing shorter duration.

Conclusion
We found no conclusive evidence supporting the use of statins in critically ill adult patients with TBI at this time. Nevertheless, the trials were limited, and wide confidence intervals resulted in significant uncertainty of the findings. A potential benefit cannot be ruled out, underscoring the need for a larger, well-designed trial.

PROSPERO registration number
CRD42023421227.

New England Journal of Medicine, Volume 392, Issue 8, Page 822-823, February 20, 2025.

Circulation, Ahead of Print. BACKGROUND:Periprocedural myocardial injury (PMI) with or without type 4a myocardial infarction (MI) might occur in patients with non–ST-segment–elevation MI (NSTEMI) after percutaneous coronary intervention (PCI). This study investigated the incidence and prognostic relevance of these events, according to current definitions, in patients with NSTEMI undergoing PCI. The best cardiac troponin I (cTnI) threshold of PMI for prognostic stratification is also suggested.METHODS:Consecutive patients with NSTEMI from January 2017 to April 2022 undergoing PCI with stable or falling pre-PCI cTnI levels were enrolled. According to the Fourth Universal Definition of Myocardial Infarction, the study population was stratified into those experiencing (1) PMI with type 4a MI, (2) PMI without type 4a MI, or (3) no PMI. Post-PCI cTnI increase >20% with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit within 48 hours after PCI was used to define PMI. The primary end point was 1-year all-cause mortality, and the secondary end point consisted of major adverse cardiovascular events at 1 year, including all-cause mortality, nonfatal reinfarction, urgent revascularization, nonfatal ischemic stroke, and hospitalization for heart failure. Internal validation was performed in patients enrolled between May 2022 and April 2023.RESULTS:Among 1412 patients with NSTEMI undergoing PCI with stable or falling cTnI levels at baseline, 240 (17%) experienced PMI with type 4a MI, 288 (20.4%) experienced PMI without type 4a MI, and 884 (62.6%) experienced no PMI. PMI was associated with an increased risk of adverse clinical outcomes, with patients with type 4a MI demonstrating the highest rates of 1-year all-cause mortality and major adverse cardiovascular events. A post-PCI ΔcTnI >20% but ≤40% showed similar outcomes to patients without PMI, whereas >40% was identified as the optimal threshold for prognostically relevant PMI, confirmed in an internal validation cohort of 305 patients.CONCLUSIONS:Periprocedural ischemic events were frequent in patients with NSTEMI undergoing PCI with prognostic implications. A post-PCI ΔcTnI >40%, combined with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit, was identified as the optimal threshold for diagnosing prognostically relevant PMI. Recognizing these events may improve risk stratification and management of patients with NSTEMI.

Introduction
Reversal treatment is commonly used for managing oral anticoagulant (OAC)-associated intracranial haemorrhages. Its effects on mortality are still understudied, particularly in various subtypes of intracranial haemorrhages. This systematic review and meta-analysis aims to synthesise the available data to study the impact of reversal therapies on mortality following various OAC-associated acute intracranial haemorrhages.

Methods and analysis
This protocol follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Protocols, and the final review will be reported in accordance with the PRISMA reporting guidelines. This systematic review and meta-analysis will include studies that assess contemporary reversal treatment in comparison to no reversal treatment, in cases of OAC-associated intracranial haemorrhage. Stratification will be performed for the types of bleeding as well as OAC at bleeding onset. Preliminary searches to determine search term inclusions were conducted in May–August 2024 in the electronic databases Embase, PubMed, Scopus and Web of Science without language and publication date restrictions. Randomised controlled studies, non-randomised controlled trials, and observational studies will be considered for the final meta-analysis. Three reviewers (MT, JOS and AB) will screen titles and abstracts, and one reviewer (MT) will subsequently conduct full-text screening.
Risks of bias will be assessed by MT using tools such as Risk of Bias 2, Risk Of Bias In Non-randomised Studies – of Interventions and the Newcastle-Ottawa Scale. Heterogeneity among the study results will be assessed using the I² statistic. If appropriate, a random-effects meta-analysis model will be performed. Subgroup analyses and meta-regression (if applicable) will be performed to assess sources of heterogeneity among (1) intracranial haemorrhage types, (2) OAC drugs and (3) study types, with randomised controlled trials being the primary focus.

Ethics and dissemination
Ethical approval is not needed as this project involves previously published data. We intend to publish the results in a peer-reviewed journal.

PROSPERO registration number
CRD42024556420.

Introduction
Sleep-disordered breathing (SDB) and the related clinical syndrome, sleep apnoea syndrome (SAS), are highly prevalent in patients with ischaemic heart disease and often remain undiagnosed. The AMI-Sleep study will describe its prevalence in patients with acute myocardial infarction (AMI) and assess the independent contribution of the type and severity of SDB/SAS to subsequent incident cardiovascular events and mortality.

Methods and analysis
This prospective study will include patients hospitalised for AMI enrolled in the multicentre nationwide prospective French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry. A nightly simplified polygraphy is performed before discharge from the index AMI admission, and participants complete two self-administered sleep questionnaires. Baseline data are obtained from the FRENCHIE registry. Each participant will be subsequently followed based on data from the National Health Data System (SNDS). Over a period of 4 years, the AMI-Sleep study is expected to recruit approximately 2000 participants. Assuming at least a 10% rate of incident cardiovascular events over 1 year, there would be an estimated 200 events during the first year of follow-up that would be sufficient in multivariable analysis. The primary objective is to describe the prevalence and severity of SDB in AMI and to analyse the association between the type and severity of SDB (based on the apnoea-hypopnoea index) and the occurrence of cardiovascular events (incident acute coronary syndrome, transient ischaemic attack, stroke) or all-cause death after AMI. Secondary objectives include determining the association between the presence of SAS and coronary artery disease severity, in-hospital mortality, morbidity events, healthcare consumption and related costs.

Ethics and dissemination
Eligible individuals are provided with information about the AMI-Sleep study and provided written informed consent. The protocol was approved by the regional Ethics Committee (CPP Ouest II – Angers, RCB N°2018-A00719-46) on 17 February 2019, is registered on ClinicalTrials.gov (NCT04064593) and started in January 2019 with the expected publication of primary outcome results in 2025.

Trial registration number
ClinicalTrials.gov, NCT04064593.

Objectives
Depression frequently occurs among individuals suffering from chronic kidney disease (CKD), diminishing life quality considerably while accelerating the disease course. This study aims to create a predictive model to identify patients with CKD at high risk for depression.

Design
Analysis of cross-sectional data.

Setting
US National Health and Nutrition Examination Survey (2007–2014).

Participants
A total of 2303 patients with CKD (weighted=17 422 083) with complete data were included in the analysis.

Outcome measures
We used the least absolute shrinkage and selection operator regression for variable selection and constructed a weighted logistic regression model through stepwise backward elimination based on minimisation of the Akaike information criterion, visualised with a nomogram. Internal validation was conducted using 1000 bootstrap resamples. Model discrimination was assessed using receiver operating characteristic curves, calibration was evaluated using the Hosmer-Lemeshow test and calibration curves, and net benefits and clinical impact were analysed using decision curve analysis and comparative impact chart curves.

Results
The final model included 10 predictors: age, gender, poverty income ratio, body mass index, smoking, sleep time, sleep disorder, chest pain, diabetes and arthritis. The model achieved an area under the curve of 0.776 (95% CI 0.745 to 0.806) with good fit (Hosmer-Lemeshow p=0.805). Interventions within the 0.1–0.6 probability range showed significant benefits.

Conclusion
We have crafted a predictive model with good discriminative power that could potentially help clinicians identify patients with CKD at high risk for depression, thereby facilitating early intervention and improving the prognosis of these patients.

Bilancio della 25/a edizione delle Giornate di raccolta del Banco Farmaceutico

Annals of Internal Medicine, Ahead of Print.