Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma.

New insights into the long-term adverse effects of antimalarials in patients with systemic lupus erythematosus.

Background: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus (SLE) because of its efficacy and safety. Previous studies of antimalarial toxicity under non-experimental conditions have often grouped hydroxychloroquine and chloroquine. This study focuses on the long-term toxicity of antimalarial drugs in SLE patients at a single reference centre.

Sources, levels, and determinants of indoor air pollutants in Europe: A systematic review.

Clean air is a requirement for life, and the quality of indoor air is a health determinant since people spend most of their daily time indoors. The aim of this study was to systematically review the available evidence regarding the sources, determinants and concentrations of indoor air pollutants in a set of scenarios under study in K-HEALTHinAIR project. To this end, a systematic review was performed to review the available studies published between the years 2013-2023, for several settings (schools, homes, hospitals, lecture halls, retirement homes, public transports and canteens), conducted in Europe, where sources and determinants of the indoor pollutants concentrations was assessed.

Measuring the impact of hospitalisation for infectious diseases on the quality of life of older patients in four European countries: the AEQUI longitudinal matched cohort study (2020-2023).

Objectives: To evaluate the impact of hospitalisation for infectious diseases on the Health-Related Quality of life (HRQOL), multidimensional frailty, and functioning of older patients, we conducted a longitudinal matched cohort study in four European countries.

Methods: HRQOL, frailty, and functioning were assessed using validated questionnaires at inclusion, at discharge, and up to six months later (M6) in patients aged over 65 years hospitalised for severe acute respiratory or bloodstream infections, and matched controls hospitalised for non-infectious conditions. Comparative analyses employed multilevel mixed-effect linear or logistic models to assess changes from inclusion.

Protocol for the enhanced management of multimorbid patients with COPD and severe asthma: role of indoor air quality.

Introduction: Reducing unplanned hospital admissions in chronic patients at risk is a key area for action due to the high healthcare and societal burden of the phenomenon. The inconclusive results of preventive strategies in patients with chronic obstructive respiratory disorders and comorbidities are explainable by multifactorial but actionable factors.The current protocol (January 2024-December 2025) relies on the hypothesis that intertwined actions in four dimensions: (1) management change, (2) personalisation of the interventions based on early detection/treatment of acute episodes and enhanced management of comorbidities, (3) mature digital support and (4) comprehensive assessment, can effectively overcome most of the limitations shown by previous preventive strategies.

The multiple facets of Rab proteins modulating the cellular distribution of cholesterol from the late endosomal compartment.

Cholesterol is an essential lipid that ensures the functional integrity of mammalian cells. Most cells acquire cholesterol via endocytosis of low-density lipoproteins (LDL). Upon reaching late endosomes/lysosomes (LE/Lys), incoming ligands, including LDL-derived cholesterol, are distributed to other organelles.

In Vitro Activity of Ampicillin Plus Ceftriaxone Against Non- and Non- Enterococcal Isolates With/Without VanC Phenotype: Clinical Implications for Infective Endocarditis.

(1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-/non- enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time-kill curves with standard (ISI) and high (IHI) inocula were performed to test isolates [3 (ECAS) and 1 (EGALL)] and non- isolates [1 (EDUR), 1 (EHIR) and 1 (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases.

Ileal Predominance in Crohn's Disease Is Associated With Increased Intestinal Surgery and Biological Therapy Use, With Lower Treatment Persistence.

Introduction: Crohn's disease (CD) varies by location, potentially affecting therapy efficacy and surgery risk, although research on this topic is conflicting. This study aims to investigate the independent association between CD location and therapeutic patterns.

Methods: We analyzed patients with CD diagnosed from January 2005 to May 2023 registered in the nationwide ENEIDA registry.

Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis.

Introduction: Very rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E.

Sellar and perisellar meningiomas: effects on pituitary function in a Spanish cohort observational study.

Purpose: Studies focused on the effects of sellar and/or perisellar (S/PS) meningiomas on pituitary function are scarce. The primary objective of the present study was to determinate the effects that S/PS meningiomas and their treatments have on pituitary function. Also, we described the clinical characteristics and therapeutic outcomes of the cohort of adult Spanish patients.

Point-of-care additive manufacturing: state of the art and adoption in Spanish hospitals during pre to post COVID-19 era.

Background: 3D technologies [Virtual and Augmented 3D planning, 3D printing (3DP), Additive Manufacturing (AM)] are rapidly being adopted in the healthcare sector, demonstrating their relevance in personalized medicine and the rapid development of medical devices. The study's purpose was to understand the state and evolution of 3DP/AM technologies at the Point-of-Care (PoC), its adoption, organization and process in Spanish hospitals and to understand and compare the evolution of the models, clinical applications, and challenges in utilizing the technology during the COVID-19 pandemic and beyond.

Methods: This was a questionnaire-based qualitative and longitudinal study.

Vascular risk factors are associated with grey matter atrophy in secondary progressive multiple sclerosis.

Background: Comorbidities including vascular risk factors can be associated with whole and regional brain atrophy in multiple sclerosis (MS). This has been examined in mixed MS cohorts in prospective or observational studies; however, the association between vascular comorbidities (VCM) in secondary progressive MS (SPMS) and brain atrophy has been less well studied. The aim was to investigate the cross-sectional and longitudinal association between VCM, comorbidity burden and brain atrophy in SPMS.

Partial biochemical response of adrenal artery embolization for pheochromocytoma: A case report and review of the literature.

We present the case of a 22-year-old male with a left adrenal pheochromocytoma, initially diagnosed during a workup for thoracic pain. The patient's tumor was refractory to medical management, and surgical resection was ruled out due to high cardiovascular risk, stemming from cyanotic congenital heart disease, aortic aneurysm, and factor VII deficiency. The patient underwent adrenal artery embolization (AAE) as a salvage treatment.

Liver stiffness measurement predicts clinical outcomes in autoimmune hepatitis.

Background & Aims: Liver stiffness measurement (LSM) has been shown to adequately predict outcomes in patients with liver disease. However, the value of LSM as a predictor of disease progression in autoimmune hepatitis (AIH) remains to be determined. This study aimed to evaluate the role of LSM as a predictor of disease progression and decompensation of cirrhosis in patients with AIH.

Prognostic Expression Signature of , , and Genes in Patients with Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors.

Unlabelled: Alterations in the tumor suppressor genes (TSGs) , , and are associated with treatment resistance, worse survival, and aggressive variants of prostate cancer (AVPC). We previously developed and validated a signature reflecting low TSG expression (TSG) that was associated with poor outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) ± docetaxel. The aim of this multicenter retrospective study was to validate the TSG signature in patients with mHSPC treated with ADT and an androgen receptor pathway inhibitor (ARPI) and to explore clinical characteristics at progression according to TSG status.

The use of 7T MRI in multiple sclerosis: review and consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

The use of ultra-high-field 7-Tesla (7T) MRI in multiple sclerosis (MS) research has grown significantly over the past two decades. With recent regulatory approvals of 7T scanners for clinical use in 2017 and 2020, the use of this technology for routine care is poised to continue to increase in the coming years. In this context, the North American Imaging in MS Cooperative (NAIMS) convened a workshop in February 2023 to review the previous and current use of 7T technology for MS research and potential future research and clinical applications.

Applicability of the adjusted morbidity groups algorithm for healthcare programming: results of a pilot study in Italy.

Background: Population-based Health Risk Assessment (HRA) tools are strategic for the implementation of integrated care. Various HRA algorithms have been developed in the last decades worldwide. Their full adoption being limited by technical, functional, and economical factors.

Connecting genomic and proteomic signatures of amyloid burden in the brain.

Background: Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease.

Methods: We performed a meta-analysis of GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n=2,076).

RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.

RTP801/REDD1 is a stress-responsive protein overexpressed in neurodegenerative diseases such as Alzheimer's disease (AD) that contributes to cognitive deficits and neuroinflammation. Here, we found that RTP801 interacts with HSPC117, DDX1 and CGI-99, three members of the tRNA ligase complex (tRNA-LC), which ligates the excised exons of intron-containing tRNAs and the mRNA exons of the transcription factor XBP1 during the unfolded protein response (UPR). We also found that RTP801 modulates the mRNA ligase activity of the complex in vitro since RTP801 knockdown promoted XBP1 splicing and the expression of its transcriptional target, SEC24D.

Antibody-mediated rejection diagnosed in early protocol biopsies in high immunological risk kidney transplant recipients.

Background: Renal transplant recipients with donor-specific anti-HLA antibodies are at an increased risk of antibody-mediated rejection (AMR). Early protocolized renal biopsies may serve as a strategy to improve diagnosis in this patient population.

Methods: We evaluated 155 highly sensitized renal transplant recipients with cPRA class I + II > 90% pre-transplant from 2015 to 2022.