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

Background
Neutrophil infiltration and hepatocyte damage are indispensable hallmarks in alcohol-associated hepatitis (AH), yet the underlying crosstalk between neutrophils and hepatocytes and its role in AH pathogenesis remain unclear.

Objective
We investigate the regulatory role of leucocyte cell-derived chemotaxin 2 (LECT2) in hepatocyte–neutrophil interaction and its impact on AH progression.

Design
We used bulk and single-cell RNA sequencing to identify hepatocyte-secreted factors targeting neutrophils. We analysed serum and liver samples from AH patients and employed genetically modified mice alongside in vitro studies.

Results
RNA-sequencing analysis identified several neutrophil chemokines that are elevated in hepatocytes from AH patients, including LECT2 whose role in AH remains largely unknown. AH patients exhibited increased levels of LECT2 in hepatocytes, positively correlating with the severity of AH. Ethanol-fed mice also exhibited elevated liver LECT2, which was abolished by inhibiting endoplasmic reticulum stress. Functional studies revealed that ethanol-induced liver injury was ameliorated in Lect2-deficient mice but was exacerbated in mice with hepatic overexpression of Lect2. Furthermore, LECT2 exacerbated ethanol-induced liver injury by promoting reactive oxygen species (ROS) through its interaction with prohibitin 2 (PHB2), a neutrophil membrane protein. By directly binding to PHB2, LECT2 disrupts the stable structure of PHB1/PHB2 heterodimerisation, consequently leading to PHB2 degradation, ROS accumulation, neutrophil activation and neutrophil extracellular trap formation. Moreover, therapeutic intervention of LECT2 via Lect2 shRNA ameliorated ethanol-induced liver injury.

Conclusion
Our studies identified a novel vicious cycle between neutrophils and hepatocytes through the LECT2–PHB2 interaction, presenting a promising therapeutic intervention by targeting LECT2 to mitigate AH in patients.

Background
Gut-liver crosstalk plays an important role in alcohol-associated liver disease (ALD) pathogenesis; but underlying mechanisms remain obscure.

Objective
We examined the regulation of intestinal and intrahepatic CD8+ T lymphocytes and their contribution to ALD.

Design
ALD patients were recruited for evaluation of intestinal and liver T cells. Single-cell RNA sequencing (scRNA seq) was performed to analyse intrahepatic and peripheral T cells in ALD. Wildtype, CD8-specific Bcl2 transgenic (Cd8 Bcl-2), and Cd8 –/– mice were subjected to chronic-plus-binge ethanol feeding.

Results
In ALD patients, duodenal CD8+ T cells were selectively reduced and negatively correlated with liver injury and bacterial translocation markers, while intrahepatic CD8+ T cells were markedly increased. ScRNA seq analysis of ALD patient livers revealed several populations of CD8+ T cells expressing activation and survival genes (eg, Bcl2). Transcriptomics and functional studies revealed a key role of prosurvival BCL2 in this opposite regulation of CD8+ T cells. Mechanistically, chronic-plus-binge ethanol feeding reduced CD8+ T cells specifically in the duodenum where ethanol levels are high. Inducing BCL2 in CD8+ T cells reversed ethanol-induced loss of duodenal CD8+ T cells, improved gut barrier function and ameliorated ALD, while CD8 deficiency was linked to enhanced neutrophil and macrophage infiltration in the liver, exacerbating ALD in mice.

Conclusions
ALD is associated with loss of duodenal CD8+ T cells but elevation of intrahepatic CD8+ T cells, which aggravates and ameliorates ALD, respectively. Restoration of survival and functions of intestinal and intrahepatic CD8+ T cells may represent a novel therapeutic strategy for ALD patients.

Background and aims
Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC.

Methods
Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients.

Results
The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission.

Conclusions
In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.

Acute severe ulcerative colitis (ASUC) remains one of the challenging presentations in inflammatory bowel disease (IBD) where progress on therapeutic approaches has been limited since 1955 when corticosteroids revolutionised care 1 to reduce the mortality associated with ASUC. Despite the advent of rescue therapy options, short- and long-term colectomy rates remain stubbornly high2 . While newer strategies to reduce the need for in-hospital colectomy during an index admission are being considered with variable success, there is limited data guiding the management of steroid-responsive patients with ASUC. In GUT, Amiot et al 3 aimed to address this gap in knowledge by randomising ASUC patients responding to intravenous steroids (IV) to infliximab with azathioprine (IFX+AZA) or azathioprine (AZA) alone. The results indicate a 28% reduction in treatment failure at week 52, defined as the composite of the absence of steroid-free clinical remission and endoscopic response…

Introduction
Liver cirrhosis accounts for over 10 000 deaths in the UK each year with a total loss of 60 000 quality-adjusted life-years. There is a substantial cost to the NHS of £4.5 billion, with new liver-related decompensation events accounting for the majority of this. Following an acute cirrhosis decompensating event, there is a significant risk of hospital readmission with 90-day readmission rates as high as 53%. Current care in the UK is reactive and patients are often only readmitted when they have presented acutely as an emergency with significant decompensation.

Methods and analysis
CirrhoCare is a prospective, multicentre, randomised controlled trial comparing the CirrhoCare management system with standard-of-care for high-risk cirrhosis patients who have been discharged following an admission with acute decompensation. The CirrhoCare management system comprises a novel digital platform for use in a patient’s home, designed to proactively detect the first signs of new decompensation in patients with established cirrhosis, discharged to the community. This enables a clinician to instigate early community-based care or, if needed, to triage the patient for hospital interventions.
214 patients will be recruited to the CirrhoCare trial from at least 12 UK centres. Patients will be randomised on a 1:1 ratio allocation to the CirrhoCare Management System or standard of care. Participants who are randomised to CirrhoCare will receive a CirrhoCare health kit comprising a smart watch, smart phone with enabled SIM (Subscriber Identity Module) network card, blood pressure monitor, weighing scales and thermometer. Participants will take measurements every morning Monday to Friday and will be followed up for 90 days postdischarge.
The primary objective of this study is to assess the clinical effectiveness of the CirrhoCare digital management system. We hypothesise that its early community-based intervention will reduce the number of unplanned hospital interventions and admissions and prevent liver-related complications when compared with standard-of-care management.

Ethics and dissemination
CirrhoCare is a National Institute for Health and Care Research-funded study (NCT06223893). The study has UK Research Ethics Committee and Health Research Authority (HRA) approvals, with approval granted by the HRA and Health and Care Research Wales committee. The results of this study will be published in peer review journals, disseminated at international conferences as well as established Patient and Public Involvement and Engagement networks.

Trial registration number
ISRCTN11380842.

Objectives
COVID-19 in children is generally of short duration, but some may take longer to recover. This study investigated the time to symptom resolution following SARS-CoV-2 infection among children in a community setting on the outskirts of an urban centre in Brazil.

Design
Prospective cohort study.

Setting
This is a community-based cohort of children living in Manguinhos, a favela in Rio de Janeiro. The cohort was followed through home visits and telephone monitoring of symptoms. The analysis focused on symptomatic children from this cohort with confirmed SARS-CoV-2 infection. Recovery time was defined as the interval between the first date with symptoms and the first date without symptoms following a positive SARS-CoV-2 test.

Participants
A total of 1276 children (boys and girls aged 2–

Prediction model at the time of allocation provides a simple and practical tool which may guide organ distribution agencies and medico-surgical teams by customizing cold ischemia time for a kidney allograft transplantation.

Caldo, afa? Anche i farmaci “soffrono”. Ma cosa accade davvero ai medicinali quando le temperature schizzano così in alto come in questi giorni?Disattenzioni come lasciare una medicina in macchina o…

Il vademecum di Aifa per i medicinali in valigia

Aifa, attenzione a quelli per ansia e ipertensione

Limitate alterazioni metaboliche indotte da farmaci psichiatrici

Strategies to optimise antimicrobial use are safe, with no negative impact on mortality or transplant-related complications, and appear to improve some clinical outcomes in SOTr, particularly when using perioperative antimicrobial prophylaxis in kidney SOTr and when implementing AMS programmes. No difference in the rate of surgical site infection was found between short and extended duration of antimicrobial prophylaxis for kidney and liver SOTr. This suggests that a shorter duration of antimicrobial surgical prophylaxis may be safe for transplant recipients.

Objectives
Modern healthcare is delivered by an increasingly multidisciplinary team, complicating workforce management. Patient safety inquiries have led to reports such as the Francis and Berwick reports (2013), which consistently emphasise the need for proper staffing to ensure patient safety. While nursing has seen progress with safe staffing guidelines, there remains a significant gap in guidance for medical staff. In the UK, consultants are the senior members of the medical profession who have achieved a Certification of Completion of Training (CCT) and are able to practice independently. The number of required consultants is based on population needs, and future consultant numbers are used to determine the number of doctor training positions. However, this approach often overlooks the specific staffing needs of individual hospitals, particularly regarding patient safety. Although a named consultant is responsible for patient care, the medical workforce that handles day-to-day operations in acute hospitals consists of a diverse group of staff who require varying degrees of supervision based on their competency and seniority. This group includes medical associates, such as physician associates, and resident doctors (formerly known as junior doctors) who themselves are a heterogeneous group needing different levels of oversight. As a result, the previous focus solely on consultant staffing requirements must be broadened to address the realities of patient care. At present, no single resource provides a comprehensive summary of staffing recommendations that includes all groups within the non-consultant medical workforce. This research aims to identify existing guidance for this part of the medical workforce to support healthcare management. The objectives of this study are, therefore, to identify guidance and recommendations for safe staffing levels from a patient safety perspective for non-consultant medical staff in UK acute hospitals.

Design
A scoping literature review was conducted and is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Data sources
This used five search strategies: internal website searches, Google Scholar searches, general Google searches, medical database searches via Ovid and a snowballing strategy.

Eligibility criteria
English-language resources published from 2015 to 2024 that provide specific guidance on safe medical staffing levels for National Health Service acute hospitals in the UK.

Data extraction and synthesis
Thematic analysis was employed to identify patterns in the diverse guidance discovered, using a hybrid approach that combined human and AI methods. The benefits and limitations of this method are discussed.

Results
The review yielded 10 703 resources, of which 10 met all eligibility criteria for analysis. Identified themes include staffing requirements, staffing recommendations and a tiered system approach.

Conclusions
Medical staffing is complex due to the varying roles and competencies involved. While some guidance exists, there is a clear need for more comprehensive recommendations that go beyond specific specialities. Future research should focus on developing a medical safe staffing tool and addressing the barriers to comprehensive guidance, both of which would enhance patient care.

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