The Theranostic Genome.

Theranostic drugs represent an emerging path to deliver on the promise of precision medicine. However, bottlenecks remain in characterizing theranostic targets, identifying theranostic lead compounds, and tailoring theranostic drugs. To overcome these bottlenecks, we present the Theranostic Genome, the part of the human genome whose expression can be utilized to combine therapeutic and diagnostic applications.

A plasmid-chromosome crosstalk in multidrug resistant enterobacteria.

Conjugative plasmids promote the dissemination and evolution of antimicrobial resistance in bacterial pathogens. However, plasmid acquisition can produce physiological alterations in the bacterial host, leading to potential fitness costs that determine the clinical success of bacteria-plasmid associations. In this study, we use a transcriptomic approach to characterize the interactions between a globally disseminated carbapenem resistance plasmid, pOXA-48, and a diverse collection of multidrug resistant (MDR) enterobacteria.

Unravelling the mechanisms causing murepavadin resistance in : lipopolysaccharide alterations and its consequences.

Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.

Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.

A worldwide assessment of the mechanical ventilation in patients with acute exacerbations of chronic obstructive pulmonary disease. Analysis of the VENTILAGROUP over time. A retrospective, multicenter study.

Background: The trend over time and across different geographical areas of outcomes and management with noninvasive ventilation or invasive mechanical ventilation in patients admitted for acute exacerbations of chronic obstructive pulmonary disease and treated with ventilatory support is unknown. The purpose of this study was to describe outcomes and identify variables associated with survival for patients admitted to an intensive care unit (ICU) with acute exacerbation of chronic obstructive pulmonary disease [aeCOPD] who received noninvasive or invasive mechanical ventilation worldwide.

Methods: Retrospective, multi-national, and multicenter studies, including four observational cohort studies, were carried out in 1998, 2004, 2010, and 2016 for the VENTILAGROUP following the same methodology.

Endoscopic sleeve gastroplasty plus lifestyle intervention in patients with MASH: a multicentre, sham-controlled, randomized trial.

Metabolic dysfunction-associated steatohepatitis(MASH) is commonly seen in biopsy proven steatotic liver disease(SLD). Life-style intervention reaching a weight loss higher than 10% promotes MASH resolution, but this goal is only achieved by a small number of patients. Endoscopic sleeve gastroplasty(ESG) has recently emerged as a safe and effective option to promote weight loss in obese population.

Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?

Background/objectives: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification.

The effect of sample site and collection procedure on identification of SARS-CoV-2 infection.

Background: Sample collection is a key driver of accuracy in the diagnosis of SARS-CoV-2 infection. Viral load may vary at different anatomical sampling sites and accuracy may be compromised by difficulties obtaining specimens and the expertise of the person taking the sample. It is important to optimise sampling accuracy within cost, safety and accessibility constraints.

Assessment of cystic fibrosis related liver disease in a pediatric cohort.

Background: Cystic fibrosis (CF) is an autosomal recessive, chronic, potentially lethal genetic disease. CF manifestations are due to mutations in the CF transmembrane receptor transporter (CFTR) gene which codes for a protein (CFTR) that acts as an anion transporter, mainly chlorine, at epithelial cells where it is expressed. Cystic fibrosis related liver disease (CFRLD) includes a spectrum of hepatobiliary manifestations whose diagnosis and follow-up remains a challenge.

Ruxolitinib in acute and chronic graft-versus-host disease: real life long-term experience in a multi-center study for adult and pediatric patients, on behalf of the GETH-TC.

Ruxolitinib has been approved for the treatment of adults and pediatric patients ≥12 years with steroid refractory graft-versus-host disease (GvHD). However, real-life studies are needed to confirm the results of clinical trials and further assess its efficacy in special populations. We performed a descriptive, retrospective, multi-center study of 352 adults and 42 pediatric patients treated with ruxolitinib for steroid-refractory acute or chronic GvHD.

[Artículo traducido] Eficacia de nuevos viscosuplementos activos en el comportamiento de un modelo experimental de osteoartritis.

Objective: To evaluate with an animal model of osteoarthritis (New Zealand rabbits) the effectiveness of treatment with active viscosupplements (hyaluronic acid loaded with nanoparticles (NPs) that encapsulate anti-inflammatory compounds or drugs.

Material And Methods: Experimental study composed of 5 groups of rabbits in which section of the anterior cruciate ligament and resection of the internal meniscus were performed to trigger degenerative changes and use it as a model of osteoarthritis. The groups were divided into osteoarthrosis without treatment (I), treatment with commercial hyaluronic acid (HA) (II), treatment with HA with empty nanoparticles (III), treatment with HA with nanoparticles encapsulating dexamethasone (IV) and treatment with HA with nanoparticles that encapsulate curcumin (V).

Fractal analysis to assess the differentiation state of oligodendroglia in culture.

Background: Oligodendroglial development is accompanied by increased cell complexity. A simple and cost-effective evaluation of the pro-myelinating activity of different drugs and/or treatments would be of great interest. In cultured oligodendroglia, an evaluation of the pro-myelinating activity of different drugs and/or treatments can be achieved through fractal analysis, which allows measuring cell complexity.

Interleukin-6 as a prognostic marker in acute kidney injury and its klotho-dependent regulation.

Background And Objective: In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI.

Ecological study to estimate the prevalence of patients with acid sphingomyelinase deficiency in Spain. PREVASMD study.

Background And Objective: Prevalence studies of acid sphingomyelinase deficiency (ASMD) are scarce and different in Spain. The objective of the present study was to determine the estimated prevalence of patients diagnosed with ASMD (types A/B and B) in Spain.

Material And Methods: PREVASMD was a descriptive, multicenter, and ecological study involving 21 physicians from different specialties (mainly Internal Medicine, Paediatrics and Hematology), of different autonomous communities, with experience in ASMD management.

The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk.

Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss.

Introduction to iodinated contrasts: Properties, intravenous administration and distribution throughout the body.

Iodinated contrast media enable greater attenuation of vascular and visceral structures in radiological studies and are widely used due to their high degree of safety, easy administration, acceptable level of tolerance, wide distribution and rapid excretion, qualities determined by their composition. Automated power injectors are used to administer contrast media. Once injected, contrast is distributed throughout the body, remaining in the intravascular space during its first passage before reaching the organs and spreading into the extracellular interstitial space, followed by a recirculation phenomenon.

Preclinical gout is common in the patient with stage 3-5 chronic kidney disease. Relevance of musculoskeletal ultrasound.

Background: One in 10 patients with hyperuricemia may develop gout over time, with urate deposition sometimes asymptomatic. Recent reviews and guidelines support ultrasound (US) to assess asymptomatic hyperuricemic (AH) patients to detect gout lesions, showing double contour (DC) and tophus the highest specificities and positive predictive values. Hyperuricemia and gout are common in chronic kidney disease (CKD), especially with glomerular filtration rate (GFR) <60, and both are associated with worse prognosis, although treatment of AH in CKD is not yet recommended in all guidelines.

Early kyphoplasty in the elderly patient.

Unlabelled: Prevalence of vertebral compression fractures is over 30 % in the elderly population. The ideal treatment for these fractures remains a subject of debate. The objective in this study is to compare the clinical outcomes of early kyphoplasty and conservative treatment in vertebral compression fractures.

Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR).

Background: There is a long-standing need for a noninvasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB).

Methods: Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT04973943). All patients underwent 7 per-protocol surveillance EMB during the first postheart transplantation year.

[Translated article] Trichotillomania Treatment Update.

Trichotillomania (TTM) is an obsessive-compulsive disorder in which affected individuals recurrently pull-out hair from any region of the body, causing hair loss or alopecia. The management of TTM is a therapeutic challenge for dermatologists and consists of a combination of pharmacological and non-pharmacological alternatives. Cognitive-behavioral therapy has successfully been used to treat TTM.