[Translated article] The relevance of therapeutic positioning in the post-approval evaluation of new drugs.

The objective of regulatory authorities is to ensure a favourable risk-benefit balance for medicines in their licenced indication, without seeking to establish their place in the therapeutic armamentarium beyond that. The licenced indication covers heterogeneous subpopulations and often does not sufficiently specify the characteristics of the patients who may benefit. The regulatory information does not always show the benefit over the standard treatment(s); moreover, it only reacts to the conditions specified in the developer's application, and lacks an assessment of the clinical relevance of the benefit and its uncertainties.

Frailty assessment in adults undergoing allogeneic hematopoietic cell transplantation: insights from a multicenter GETH-TC study to optimize outcomes and care.

Introduction: This multicenter prospective study sponsored by the (GETH-TC) explores the use of frailty assessments in allo-HCT candidates.

Methods: Frailty was measured using the HCT Frailty Scale at first consultation and HCT admission in 404 adults from 15 HCT programs in Spain. Based on the results, patients were classified into fit, pre-frail and frail categories.

Comprehensive Clinical and Genetic Characterization of a Spanish Cohort of 22 Patients With Bainbridge-Ropers Syndrome.

Bainbridge-Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the ASXL3 gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype-phenotype correlation.

[Position statement of the Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the management of inflammatory bowel disease in Primary Care].

Primary Care is the first point of contact for most patients after the onset of symptoms of inflammatory bowel disease (IBD). Establishing an initial diagnostic process based on compatible symptoms and agreed criteria and referral pathways, depending on the degree of suspicion and the patient's situation, can reduce diagnostic delays. Once the patient is referred to the Digestive specialist and the diagnosis of IBD is established, a treatment and follow-up plan is structured.

Intraventricular thrombus in Takotsubo syndrome: Incidence, predictors, management, and prognosis. Insights from the RETAKO registry.

Background: Takotsubo syndrome (TTS) is characterized by transient left ventricular (LV) dysfunction and wall motion abnormalities without culprit coronary artery disease. LV thrombus (LVT) formation during the acute phase is a fearsome complication.

Objectives: To identify factors associated with LVT and its prognostic impact in TTS patients.

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Atopic dermatitis (AD) is a chronic, inflammatory skin disease affecting all age groups, particularly children. This systematic review provides an overview of the humanistic and economic disease burden in the pediatric population with AD in Spain. The evidence, collected from 11 observational studies published over the past 10 years, exhibits the most common characteristics of the patients, disease burden, patient-reported outcomes, use of resources, and treatment patterns.

An exosome-based liquid biopsy predicts depth of response and survival outcomes to cetuximab and panitumumab in metastatic colorectal cancer: The EXONERATE Study.

PURPOSE EXONERATE (EXOsome and cell-free micro-RNAs of anti-EGFR ResistAnce) was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with newly diagnosed RAS-WT, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in 2-nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRC to predict PFS, OS, and ORR.

Challenges in the diagnosis and follow-up of Cushing's syndrome: Evaluating LC-MS/MS as a confirmation method for urinary free cortisol analyses.

24-h urinary free cortisol (UFC) measurements are fundamental in the diagnosis and follow-up of Cushinǵs syndrome (CS) and immunoassays (IA) are the most widely used tests for its quantification in clinical laboratory practice. However, their suitability has been questioned mainly due to their limitations concerning analytical specificity. The aim of this research project was to evaluate a novel algorithm for CS diagnosis and follow-up in the clinical laboratory, based on the combination of IA tests with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for UFC quantification.

Tailored-surgery for locally advanced colon cancer based on 3D mathematical reconstruction surgical planner: Observational comparative non-randomized study.

Background: This study investigates the effectiveness of a three-dimensional reconstruction mathematical model (3D-IPR) for preoperative planning in locally advanced colon cancer (LACC) with threatened surgical margins. The objective was to evaluate the utility of a 3D-IPR surgical planner tool in cases of LACC with threatened surgical margins. Additionally, the study aims to compare the diagnostic accuracy of the 3D-IPR model against conventional CT scans in determining the infiltration of neighboring structures.

Towards the integrated care of COPD, asthma and bronchiectasis: description and objectives of a treatable trait-based complex obstructive airway disease unit.

Introduction: Expert management of Complex Obstructive Airway Diseases (COAD) requires knowledge, resources, and skills that are commonly shared in the management of the different conditions usually included in the acronym, namely asthma, bronchiectasis, and Chronic Obstructive Pulmonary Disease (COPD). We discuss the basis to shift the paradigm of single-disease management into a holistic approach and describe its potential benefits.

Areas Covered: The prevalence and significance of the overlap between the different conditions is reviewed.

Destination Therapy Strategies of Advanced Heart Failure in Elderly Non-Heart Transplant Candidates: A Propensity Matching Analysis from the LEVO-D and REGALAD Registries.

Heart transplantation (HT) is the gold standard therapy for advanced heart failure (ADHF), and LVADs as destination therapy are an option in non-HT candidates. Most patients with ADHF never receive HT or an LVAD, so alternative strategies are needed. Intermittent levosimendan can reduce HF hospitalizations in ADHF patients in the short term.

Increased Risk of Myositis-Specific and Myositis-Associated Autoantibodies After COVID-19 Pandemic and Vaccination: A Spanish Multicenter Collaborative Study.

: Emerging evidence suggests that SARS-CoV-2 infection and vaccines may trigger autoimmune responses in predisposed individuals. Idiopathic inflammatory myopathies (IIMs) are diseases with diverse clinical manifestations, often associated with myositis autoantibodies (MAs). Diagnosing IIM is challenging due to limitations in classification criteria and diagnostic assays.

Cyclic Peptide MV6, an Aminoglycoside Efficacy Enhancer Against .

: is a globally emerging pathogen with widespread antimicrobial resistance driven by multiple mechanisms, such as altered expression of efflux pumps like AdeABC, placing it as a priority for research. Driven by the lack of new treatments, alternative approaches are being explored to combat its infections, among which efficacy-enhancing adjuvants can be found. This study presents and characterizes MV6, a synthetic cyclic peptide that boosts aminoglycoside efficacy.

Use of the MNCD Classification to Monitor Clinical Stage and Response to Levodopa-Entacapone-Carbidopa Intestinal Gel Infusion in Advanced Parkinson's Disease.

Background And Objective: Staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (Motor; Non-motor; Cognition; Dependency) and five stages, correlated with disease severity, patients' quality of life and caregivers' strain and burden. Our aim was to apply the MNCD classification in advanced PD patients treated with device-aided therapy (DAT).

Patients And Methods: A multicenter observational retrospective study of the first patients to start the levodopa-entacapone-carbidopa intestinal gel (LECIG) in Spain was performed (LECIPARK study).

Extensive scalp soft-tissue reconstruction with free flaps: A simplified therapeutic algorithm for donor site selection based on a retrospective analysis.

Introduction: Extensive scalp defects present a significant reconstructive challenge due to the complex needs of patients that are often beyond the scope of conventional therapies, which makes free flaps the most reliable solution. Despite the variety of free flaps available for such cases, there is a lack of clear criteria for selecting the most suitable option. The primary objective of this study was to provide a simplified guide for the selection of donor sites for free flaps for achieving optimal reconstruction outcomes.

The role of bronchial biopsy in the prediction of response to biological therapy in severe uncontrolled asthma: a prospective study.

Background: Up to two thirds of patients with severe uncontrolled asthma (SUA) who received biological therapy do not have a complete response.

Research Question: Can bronchial biopsy (BB) play a role in the identification of patients with SUA who has a better response to biological therapy?

Study Design: AND METHODS: Prospective multicentre study. Consecutive SUA patients candidate to biological therapy underwent bronchoscopy and BB prior to biological therapy and clinical response was evaluated 6 months later.

A multirange paper-based analytical device for identifying low, moderate, and high P. aeruginosa bacterial loads in sputum samples.

In this article we introduce a multirange analytical device that extends the dynamic range of nanoparticle-based immunoassays thanks to a multisensor design. Multirange devices contain low- and high-range sensors in the same analytical platform. The low-range sensor defines the limit of detection and quantifies low concentrated analytes, whereas the high-range sensor defines the upper limit of the dynamic range.

Differential contribution of PBP occupancy and efflux on the effectiveness of β-lactams at their target site in clinical isolates of Neisseria gonorrhoeae.

Neisseria gonorrhoeae exhibits alarming antibiotic resistance trends and poses a significant challenge in therapeutic management. This study aimed to explore the association of penA alleles with penicillin-binding protein (PBP) occupancy patterns and reduced outer membrane permeability, impacting susceptibility to last-line cephalosporins and potential β-lactam candidates. The whole genome sequence, the MICs and PBP IC50s were determined for 12 β-lactams and β-lactamase inhibitors in 8 clinical isolates with varying β-lactam sensitivity, 2 ATCC, and 3 WHO cephalosporin-resistant reference strains.

potentiation of tetracyclines in by RW01, a new cyclic peptide.

The pipeline for new drugs against multidrug-resistant remains limited, highlighting the urgent need for innovative treatments. New strategies, such as membrane-targeting molecules acting as adjuvants, aim to enhance antibiotic effectiveness and combat resistance. RW01, a cyclic peptide with low antimicrobial activity, was selected as an adjuvant to enhance drug efficacy through membrane permeabilization.

Long-term effectiveness and tolerability of dolutegravir/lamivudine in treatment-naive people with HIV: an analysis of a multicentre cohort at 96 weeks.

Objectives: To evaluate the long-term effectiveness, persistence and tolerability of dolutegravir (DTG)/lamivudine (3TC), compared with the most frequently prescribed first-line treatment regimens, among antiretroviral-naive people with HIV from CoRIS, a multicentre cohort in Spain, in 2018-23.

Methods: We used multivariable regression models to compare viral suppression (VS) (HIV RNA viral load <50 copies/mL), change in CD4 cell counts, persistence and treatment discontinuations due to adverse events (AEs), at 96 (±24) weeks after treatment initiation.

Results: Of 2359 participants, DTG/3TC was prescribed in 472 (20.

3D-reconstruction printed models and virtual reality improve teaching in oncological colorectal surgery.

Background: This study aimed to evaluate the use of 3D image processing and reconstruction (3D-IPR) combined with virtual reality (VR) technology and printed models (PM) as teaching tools in oncological colorectal surgery.

Methods: We designed two courses, one for general surgery trainees and another for young colorectal surgeons, structured around stations of pre-test, anatomical lessons, real-case presentations, 3D-IPR models, VR experiences, and life-size abdominal PM with surgical approach explanations and a final post-test.

Results: Fourteen course participants were evaluated.

[Translated article] National survey and consensus document on dosing strategies for beta-lactam antibiotics against multidrug-resistant gram-negative bacilli (MDR-GNB) in critically ill patients undergoing extracorporeal life-support techniques: The DOSEBL study protocol.

Introduction: Infections caused by multidrug-resistant gram-negative bacilli (MDR-GNB) in critically ill patients present a challenge for timely and appropriate antibiotic treatment. This is particularly important in patients undergoing extracorporeal life-support techniques such as renal replacement therapy and extracorporeal membrane oxygenation. These techniques can introduce additional pharmacokinetic alterations, potentially leading to suboptimal exposure to antibiotics.