Search Results for: Nuovi farmaci per il danno renale acuto (Acute kidney injury – AKI)

This individual participant data meta-analysis compares the association between antipsychotic (vs placebo) acute-phase treatment and outcomes in individuals who were not recently treated to recently treated individuals.

This cohort study evaluates the association between sodium-glucose cotransporter 2 inhibitors and hyperkalemia in individuals with diabetes, heart failure, or chronic kidney disease receiving renin-angiotensin-aldosterone system inhibitors.

To the Editor A recent Editorial by editors representing the International Committee of Medical Journal Editors (ICMJE) highlighted the pressing issues surrounding predatory journals. Although the challenges posed by predatory journals are not new, they are becoming increasingly acute. Although some resources are in place to help counter their activities, we believe that the ICMJE could further address these issues. The ICMJE’s current practice of listing journals that self-declare adherence to the ICMJE recommendations may be exploited by predatory journals because this declaration does not guarantee adherence to the required standards.

Respiratory syncytial virus (RSV) vaccine effectiveness was approximately 75% for preventing acute respiratory infection among adults aged 60 years or older in a case-control study assessing real-life outcomes among approximately 780 000 people. This performance was comparable with efficacy in clinical trials, the researchers reported in JAMA Network Open.

This cohort study assesses the frequency of screen completion and the prevalence and outcomes of delirium diagnosis for older patients with unplanned admission to acute general (internal) medicine.

To the Editor The solutions proposed by Ms Istvan and colleagues for the administrative costs plaguing US health care will not meaningfully improve timely access to medically necessary care for individuals, or reduce moral injury among clinicians. Administrative burdens arise from obstruction by design.

This study compares proportions of facilities receiving penalties based on stratified benchmarks in the Centers for Medicare & Medicaid Services’ End-Stage Renal Disease Treatment Choices (ETC) model, a pay-for-performance program incentivizing home dialysis and kidney transplant waitlisting.

Introduction
Sepsis-induced left ventricular (LV) dysfunction participates in cardiovascular dysfunction and associated organ failure in patients with septic shock. The tested hypothesis is that dobutamine will reduce tissue hypoperfusion and secondary organ dysfunction in increasing oxygen delivery in fluid-filled patients with septic shock and associated symptomatic septic cardiomyopathy with documented low-flow state.

Methods and analysis
ADAPT–Dobutamine is a blinded, two parallel group, add-on, multicentre, randomised 1:1 and placebo-controlled trial. Patients will be included if hospitalised in the intensive care unit with septic shock (Sepsis-3 definition) and septic cardiomyopathy, identified using echocardiography (LV ejection fraction ≤40% and LV outflow tract velocity–time integral 130 bpm, severe ventricular arrhythmia, obstructive cardiomyopathy, severe aortic stenosis, ongoing acute coronary syndrome and indication for extracorporeal life support. Primary outcome will be the evolution of a modified Sequential Organ Failure Assessment score (excluding the neurologic system) during the initial intensive care unit stay encompassing screening (before randomisation), and from Day 1 to 3 after randomisation. Randomisation will be stratified on participating centres and previously documented heart failure (ejection fraction ≤40%). The use of open-labelled Dobutamine as a rescue therapy will be allowed in refractory shock based on strict clinical requirements. The use of alternative inotropes will not be allowed.

Ethics and dissemination
Approved by the Comité de Protection des Personnes Nord-Ouest IV from Lille (France) on 19 December 2019 (approval reference #19.04.05.36321). The results will be published in a peer-reviewed journal and presented in various congresses.

Trial registration number
NCT04166331.

Objectives
The inflammatory response from acute infection may trigger cardiovascular events. We aimed to estimate associations between microbiologically confirmed urinary tract infections (UTIs) and first acute myocardial infarction (MI) and stroke.

Design
We used a self-controlled case series, with risk periods 1–7, 8–14, 15–28 and 29–90 days after UTI. Included individuals experienced the outcome and exposure of interest and acted as their own controls.

Setting
We used individually linked general practice, hospital admission and microbiology data for the population of Wales held by the Secure Anonymised Information Linkage databank.

Participants
Included individuals were Welsh residents aged over 30 years with a record of a hospital admission for MI or stroke (outcomes) and evidence of a microbiologically confirmed UTI (exposure) during the study period of 1 January 2010 to 31 December 2020.

Main outcome measures
The primary outcome was acute MI or stroke identified using the International Classification of Disease V.10 codes from inpatient diagnoses recorded in the Patient Episode Database for Wales. We used Poisson regression to estimate incidence rate ratios (IRRs) and 95% CIs for MI and stroke during predefined risk periods, compared with baseline periods.

Results
During the study period, 51 660 individuals had a hospital admission for MI, of whom 2320 (4.5%) had 3900 microbiologically confirmed UTIs, and 58 150 had a hospital admission for stroke, of whom 2840 (4.9%) had 4600 microbiologically confirmed UTIs. There were 120 MIs during risk periods and 2190 during baseline periods, with an increased risk of MI for 1–7 days following UTI (IRR 2.49, 95% CI (1.65 to 3.77)). There were 200 strokes during risk periods and 2640 during baseline periods, with an increased risk of stroke for 1–7 days following UTI (IRR 2.34, 95% CI (1.61 to 3.40)).

Conclusions
UTI may be a trigger for MI or stroke. Further work is needed to understand mechanisms and test interventions to reduce the risk of cardiovascular events among people with UTIs in primary care.

Circulation, Ahead of Print. BACKGROUND:Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)–mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions.METHODS:Single-nucleus RNA sequencing analysis was performed to delineate the expression patterns of Mtus1 in human cardiomyocytes under ischemic stress. MI models were induced in mice by left coronary artery ligation and replicated in vitro using primary neonatal rat ventricular myocytes exposed to oxygen glucose deprivation. Cardiac-specific deletion of Mtus1 was achieved by crossing floxed Mtus1 mice with the Myh6-MerCreMer mice. The impact of Mtus1A, a mitochondrial isoform of Mtus1, on cardiac function and the molecular mechanisms were investigated in both in vivo and in vitro settings. Mitochondria-associated ER membranes coupling levels were evaluated by transmission electron microscopy and live-cell imaging. Protein interactions involving Mtus1A were explored through immunoprecipitation–mass spectrometry, coimmunoprecipitation, and proximity ligation assay. The roles of Mtus1A and Fbxo7 (F-box protein 7) were validated in a murine MI model using adeno-associated virus serotype 9 (AAV9).RESULTS:Bioinformatics analysis revealed a significant downregulation of Mtus1 expression in human cardiomyocytes under ischemic conditions, indicating its potential role in stress response. The predominant isoform in murine cardiomyocytes, Mtus1A, showed reduced expression in the left ventricle of mice after MI, which is consistent with the decreased levels of its orthologs in heart tissues from patients with MI. Cardiac-specific knockout of Mtus1 in mice exacerbated cardiac dysfunction after MI. Both in vitro and in vivo studies demonstrated the vital role of Mtus1A in modulating mitochondria-associated ER membranes coupling and preserving mitochondrial function. Mechanistically, Mtus1A functions as a scaffold protein that maintains the formation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1)–glucose-regulated protein 75 (Grp75)–voltage-dependent anion channel 1 (VDAC1) complex through its amino acid sequence 189-219. In addition, Mtus1A protein is stabilized by K6-linked ubiquitination through the E3 ubiquitin ligase Fbxo7. Mtus1A overexpression in mice mitigated MI-induced cardiac dysfunction and remodeling by maintaining ER-mitochondria connectivity.CONCLUSIONS:Our study demonstrates that Mtus1A is crucial for modulating MI-induced cardiac remodeling by preserving ER-mitochondria communication and ameliorating mitochondrial function in cardiomyocytes. Mtus1A may serve as a potential therapeutic target for treating heart failure after MI.

Introduction
Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prophylaxis in non-valvular atrial fibrillation. Yet, DOAC use is regarded as a contraindication for intravenous thrombolysis in acute ischaemic stroke. The stratification of patients into ‘on-therapy’ and ‘off-therapy’ categories based on their plasma DOAC concentrations is particularly crucial in the acute phase of stroke when decisions for thrombolysis or anticoagulation reversal are time-sensitive. The novel point-of-care DOAC dipstick assay (DOASENSE) rapidly assesses urine for clinically significant DOAC levels, potentially broadening eligibility for thrombolysis or targeted reversal therapy. This multicentre prospective observational registry study aims to evaluate the accuracy and clinical utility of DOAC dipstick testing compared with plasma DOAC assays in acute stroke management across regional Australian hospitals.

Methods and analysis
This multicentre, prospective, observational study will enrol participants presenting to hospitals across Victoria and Tasmania with acute ischaemic stroke or intracerebral haemorrhage with DOAC ingestion within 48 hours of presentation. Plasma DOAC concentrations measured by chromogenic assays will be compared with rapid urine dipstick results from DOASENSE testing. There is a target sample size of 146 participants. The primary outcomes are as follows: (1) proportion of ischaemic stroke participants with off-therapy plasma DOAC levels and (2) eligibility for reperfusion therapy based on DOASENSE and plasma DOAC concentrations. Secondary outcomes are follows: (1) ischaemic stroke aetiology for participants with on-therapy vs off-therapy DOAC levels; (2) proportion of participants meeting criteria for pharmacological DOAC reversal based on DOASENSE outcomes; (3) incidence of false-negative and false positive DOASENSE results in clinically significant DOAC plasma concentrations at a threshold of ≥30 ng/mL and (4) an exploratory analysis of any false negative DOASENSE assays to identify potential contributing factors.

Ethics and dissemination
Ethics approval has been granted by the Eastern Health Human Research Ethics Committee (reference number: 99628). Dissemination of findings will occur through peer-reviewed publications and academic conferences.

Objective
To develop and validate a prediction model of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL).

Design
A single-centre retrospective study.

Participants
This study analysed 471 newly diagnosed patients with ALL at the Second Affiliated Hospital of Army Medical University from January 2014 to December 2023.

Methods
Clinical and laboratory parameters were collected, and the important characteristic parameters were selected using BorutaShap. Multiple machine learning (ML) models were constructed and optimised by using the active learning (AL) algorithm. Performance was evaluated using the area under the curve (AUC), comprehensive indicators and decision curve analysis. The interpretability of the model was evaluated by using SHapley Additive Interpretation (SHAP), and external validation was conducted on an independent test cohort.

Results
10 parameters were selected to construct multiple ML models. The CatBoost model integrated with an AL algorithm (CatBoost-AL) was found to be the most effective model for predicting Ph+ALL within the validation data set. This model achieved an AUC of 0.797 (95% CI 0.710 to 0.884), along with sensitivity, specificity and F1 score of 0.667, 0.864 and 0.777, respectively. The prediction performance of CatBoost-AL was further validated with an external testing set, where it maintained a strong AUC of 0.794 (95% CI 0.707 to 0.881). Using SHAP for global interpretability analysis, age, monocyte count, -glutamyl transferase, neutrophil count and alanine aminotransferase were identified as crucial parameters that significantly influence the diagnostic accuracy of CatBoost-AL.

Conclusion
An interpretable ML model and online prediction tool were developed to determine whether newly diagnosed patients with ALL are Ph+ALL. The key parameters identified by the optimal model provided a further understanding of Ph+ALL characteristics and were valuable for accurate diagnosis and treatment of Ph+ALL.

Introduction
Delays in getting injured patients to the hospital in a timely manner can increase avoidable death and disability. Like many low-income or middle-income countries, Rwanda experiences delays related to a lack of efficient prehospital communication and formal guidelines to triage patients for hospital care. This study describes the protocol to develop, roll-out and evaluate the effectiveness of a destination decision support algorithm (DDSA) integrated in an electronic communication platform, ‘912Rwanda’. The DDSA will facilitate the linkage of patients to health facilities able to treat their condition(s).

Methods and analysis
Work will be conducted in the prehospital emergency service ‘Service d’Aide Médicale Urgente’ and health facilities in Kigali city and Musanze district, which serve predominantly urban and rural populations, respectively. We will develop interfaces to capture facility and patient-relevant data, which feed into a guideline-based electronic DDSA to match patients to hospitals. We will assess existing trauma care processes using qualitative and quantitative methodologies. This will be followed by a series of consensus workshops to develop at-scene triage guidelines and agree on variables to capture in the interfaces. The DDSA will be developed based on outputs from these workshops and will be tested against historical ambulance data and expert opinion until acceptable thresholds of performance are achieved. User interfaces will be developed and tested using human–computer interface design principles.

Discussion
The combined collaborative approach of bringing together experts and software developers, and with deep engagement of Rwandan stakeholders, including leadership of Rwanda Ministry of Health through its technical arm, Rwanda Biomedical Center, should lead to an ambulance communication system which is used, sustained and effective.

Ethics and dissemination
The project was approved by the Rwanda National Research Ethics Committee. Annual reports will be disseminated to relevant stakeholders, followed by the public. Publications will be open access as per the funding policy.

Trial registration number
ISRCTN97674565. Registered on 29 July 2024. https://doi.org/10.1186/ISRCTN97674565.