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We present the case of a 52-year-old male, with a recent history of travel to Ghana, who was admitted to the ICU due to septic shock caused by severe malaria, with a parasitaemia index of 50 %. He received treatment with intravenous artesunate followed by dihydroartemisinin (40 mg) plus piperaquine (320 mg). Despite presenting with multiorgan failure upon admission, the patient demonstrated significant clinical improvement and a rapid clearance of parasitaemia, with a parasitaemia index of 0 % at 72 h after treatment's initiation. However, he developed severe anaemia with haemoglobin levels as low as 5.6 g/dL, requiring multiple blood transfusions. The patient's anaemia was attributed to post-artesunate haemolytic anaemia (PDAH), based on a history of high parasitaemia levels and the onset of symptoms following artemisinin-based therapy. This conclusion was supported by a positive Coombs' test and elevated haemolytic markers. PDAH is likely caused by the pitting phenomenon, combined with the potential bone marrow suppression or drug-induced, antibody-mediated haemolysis. The patient received oral steroids for their capacity to suppress the immune response driving erythrocyte destruction in PDAH, resulting in a gradual recovery of haemoglobin levels. This case highlights the importance of recognizing PDAH in patients with severe malaria and high parasitaemia. Prompt diagnosis and management of haemolytic complications are crucial for recovery., (Copyright © 2025. Published by Elsevier B.V.)

Background and Aims: Parenteral nutrition (PN) composition could play a role in the management of systemic inflammatory response and intestinal barrier disruption. We aimed to evaluate changes in biomarkers of inflammation, oxidative status and intestinal permeability in patients with type 2 diabetes mellitus (T2DM) who received different PN lipid formulas., Methods: This was a prospective study, including 94 patients with T2DM who received omega (n)-3 polyunsaturated fatty acids (PUFA)-enriched PN, a mixture of medium and long chain triglycerides (MCT/LCT) PN, or an olive oil-based PN. Serum levels of biomarkers of oxidative status, intestinal permeability and inflammation biomarkers were determined at day 1 and day 5 after PN initiation. Registered under ClinicalTrials.gov Identifier no. NCT02706119., Results: At day 5 after the onset of PN, the MCT/LCT group had a significant reduction of 2 proinflammatory cytokines [interleukin (IL)-15, IL-17A], elevation of the anti-inflammatory cytokine IL-13 and increase of zonulin and indoxylsulfate. The olive oil group showed a statistically significant reduction of 5 proinflammatory cytokines [IL-1β, IL-17A, IL-6, cytokine-leukemia inhibitory factor (LIF) and tumor necrosis factor alpha (TNF-α)] and reduced concentrations of the anti-inflammatory cytokine IL-1RA, while the n-3 PUFA-enriched group presented a statistically significant reduction of 8 proinflammatory cytokines (interferon-gamma, IL-1β, IL-15, IL-17A, IL-6, LIF, monocyte chemoattractant protein 1, and TNF-α). In the between-group comparisons, indoxylsulfate significantly increased in the MCT/LCT group compared to the n-3 PUFA-enriched group, while 8-isoprostane and indoxylsulfate significantly increased in the MCT/LCT group compared to the other groups and superoxide dismutase significantly decreased in the MCT/LCT group compared to the other groups., Conclusion: In patients with T2DM, PN lipid composition exerts a profound impact on proinflammatory, prooxidative and intestinal permeability biomarkers., Competing Interests: Conflict of interest The authors have declared that no competing interests exist., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Obesity hypoventilation syndrome (OHS) is associated with high morbidity and mortality. There are few data on whether there are gender differences in outcomes., Research Question: Do women with OHS experience worse outcomes in ambulatory and hospitalized settings compared to men?, Study Design and Methods: Post hoc analyses were performed on two separate OHS cohorts: (1) stable ambulatory patients from the two Pickwick randomized controlled trials; and (2) hospitalized patients with acute-on-chronic hypercapnic respiratory failure from a retrospective international cohort. We first conducted bivariate analyses of baseline characteristics and therapeutics between genders. Variables of interest from these analyses were then grouped into linear mixed effects models, Cox proportional hazards models, or logistic regression models to assess the association of gender on various clinical outcomes., Results: The ambulatory prospective cohort included 300 patients (64% self-identified as women), and the hospitalized retrospective cohort included 1,162 patients (58% self-identified as women). For both cohorts, women were significantly older and more obese than men. Compared with men, baseline Paco 2 was similar in ambulatory patients but higher in hospitalized women. In the ambulatory cohort, in unadjusted analysis, women had increased risk of emergency department visits. However, gender was not associated with the composite outcome of emergency department visit, hospitalization, or all-cause mortality in the fully adjusted model. In the hospitalized cohort, prescription of positive airway pressure was less prevalent in women at discharge. In unadjusted analysis, hospitalized women had a higher mortality at 3, 6, and 12 months following hospital discharge compared with men. However, after adjusting for age, gender was not associated with mortality., Interpretation: Our findings indicate that although the diagnosis of OHS is established at a more advanced age in women, gender is not independently associated with worse clinical outcomes after adjusting for age. Future studies are needed to examine gender-related health disparities in diagnosis and treatment of OHS., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: In patients with ischemic heart disease, coronary microvascular dysfunction is associated with cardiovascular risk factors and poor prognosis; however, data from healthy individuals are scarce., Objectives: The purpose of this study was to assess the impact of cardiovascular risk factors and subclinical atherosclerosis on coronary microvascular function in middle-aged asymptomatic individuals., Methods: Myocardial perfusion was measured at rest and under stress using cardiac magnetic resonance in 453 individuals and used to generate myocardial blood flow (MBF) maps and calculate myocardial perfusion reserve (MPR). Subclinical atherosclerosis was assessed using 3-dimensional vascular ultrasound of the carotid and femoral arteries and coronary artery calcium scoring at baseline and at 3-year follow-up., Results: Median participant age was 52.6 years (range: 48.9-55.8 years), and 84.5% were male. After adjusting for age and sex, rest MBF was directly associated with the number of the metabolic syndrome components present (elevated waist circumference, systolic and diastolic blood pressure, fasting glucose, and triglycerides and low high-density lipoprotein cholesterol), insulin resistance (homeostatic model assessment for insulin resistance), and presence of diabetes. MPR was reduced in the presence of several metabolic syndrome components, elevated homeostatic model assessment for insulin resistance, and diabetes. Stress MBF was inversely associated with coronary artery calcium presence and with global plaque burden. Higher stress MBF and MPR were associated with less atherosclerosis progression (increase in plaque volume) at 3 years., Conclusions: In asymptomatic middle-aged individuals free of known cardiovascular disease, the presence of cardiometabolic risk factors and systemic (poly-vascular) subclinical atherosclerosis are associated with impaired coronary microvascular function. Better coronary microvascular function reduces atherosclerosis progression at follow-up. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)., Competing Interests: Funding Support and Author Disclosures The PESA study is funded by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Santander Bank. Dr Ibanez is supported by the European Commission (grant numbers ERC-CoG 819775 and H2020-HEALTH 945118), La Caixa Foundation (HR22-00533, DIREQT2Heart), the Spanish Ministry of Science and Innovation (PID2019-110369RB-I00), and the Red Madrileña de Nanomedicina en Imagen Molecular-Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). Dr Devesa is an Alfonso Martin Escudero fellow and is scientifically supported by La Caixa Foundation. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MICIU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/10.13039/501100011033). Dr Sánchez-González is a Philips employee. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Skin in vitro models offer much promise for research, testing drugs, cosmetics, and medical devices, reducing animal testing and extensive clinical trials. There are several in vitro approaches to mimicking human skin behavior, ranging from simple cell monolayer to complex organotypic and bioengineered 3-dimensional models. Some have been approved for preclinical studies in cosmetics, pharmaceuticals, and chemicals. However, development of physiologically reliable in vitro human skin models remains in its infancy. This review reports on advances in in vitro complex skin models to study skin homeostasis, aging, and skin disease., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic vasculitis encompasses a wide range of conditions characterized by varying degrees of inflammation in blood vessels. Although the etiology of vasculitis remains unclear, accumulated data suggest that it is triggered in genetically predisposed individuals by the concurrence of certain environmental factors. The importance of the genetic component has been consistently supported by evidence of familial aggregation, differential prevalence by ethnicity, and multiple genetic associations with disease susceptibility and severity reported in recent years. The strongest association signals in most vasculitides correspond to genetic variants within the HLA region, suggesting an important role of the immune system in its pathophysiology. However, each type of vasculitis has distinct defining HLA association markers, likely due to disease-specific differences in antigenic drivers. Furthermore, other genetic polymorphisms located outside the HLA region play an important role in susceptibility to different vasculitides. More recent research has assessed the shared genetic susceptibility evident across different vasculitides. Future studies should focus on the identification of genetic markers that can serve as reliable biomarkers for early diagnosis, prognosis, and treatment response in systemic vasculitis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest related to this study., (Copyright © 2024. Published by Elsevier Ltd.)

The gene editing field has advanced rapidly since the development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system because of its applicability in precisely modifying the genome. Among its multiple applications, the correction of genetic diseases has emerged as a potential curative treatment for many disorders that have eluded a cure to date. Despite its efficiency in achieving therapeutic levels of correction, the unexpected adverse effects of editing due to CRISPR/Cas9 nuclease activity are a major concern when translating these new strategies to the clinic. Multiple in silico tools and empirical methods have been developed to evaluate these off-target edits as well as other adverse alterations of the genome, including rearrangements, not only in ex vivo experiments but also in in vivo experiments. In this review, we summarize the available methods for the assessment of off-target effects of CRISPR/Cas9 systems, highlighting their advantages and limitations. Special attention will be paid to their application in pre-clinical studies and clinical trials, both in the manufacturing product and in the long-term follow-up of patients., Competing Interests: Declaration of competing interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest PR has licensed medicinal products and receives funding and equity from Rocket Pharmaceuticals.

Purpose: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems., Methods: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay)., Results: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization., Conclusion: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hector J Aguado reports financial support was provided by AO Foundation. Hector J Aguado reports financial support was provided by Government of Castile and Leon Ministry of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This review presents a comprehensive comparative analysis of international guidelines for managing advanced, non-functioning, well-differentiated pancreatic neuroendocrine tumors (panNETs). PanNETs, which represent a significant proportion of pancreatic neuroendocrine neoplasms, exhibit diverse clinical behaviors and prognoses based on differentiation, grading, and other molecular markers. The varying therapeutic strategies proposed by different guidelines reflect their distinct emphases and regional considerations, such as the ESMO guideline's focus on advanced disease management and the ENETS guidance paper's multidisciplinary approach. This review examines the most recent guidelines from ESMO, NCCN, ASCO, ENETS, and NANETS, analyzing the recommendations for first-line therapies and subsequent treatment pathways in different clinical scenarios. Significant variations are observed in the recommendations, particularly concerning the choice and sequence of systemic therapies, the role of tumor grading and the Ki-67 index in therapeutic decisions, and the integration of regional regulatory and clinical practices. The analysis highlights the need for a tailored approach to managing advanced NF panNETs, advocating for flexibility in applying guidelines to account for individual patient circumstances and the evolving evidence base. This work underscores the complexities of managing this patient population and the critical role of a multidisciplinary team in optimizing treatment outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Angela Lamarca declares travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan, Delcath Advanz Pharma and Roche. Speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA/Novartis, QED, Servier, Astra Zeneca, EISAI, Roche, Advanz Pharma and MSD; advisory and consultancy honoraria from EISAI, Nutricia, Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, AstraZeneca, Boehringer Ingelheim, GENFIT, TransThera Biosciences, Taiho and MSD; principal Investigator-associated Institutional Funding form QED, Merck, Boehringer Ingelheim, Servier, Astra Zeneca, GenFit, Panbela Therapeutics, Novocure GmbH, Camurus AB, Albireo Pharma, Taiho, TransThera, Jazz Therapeutics and Roche; she was also a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Nicola Fazio: IPSEN, Advisory Board, Personal; Merck, Advisory Board, Personal; MSD, Advisory Board, Personal; NOVARTIS, Other, Personal, Steering committee; NOVARTIS, Invited Speaker, Personal; NOVARTIS, Advisory Board, Personal; Astellas, Local PI, Institutional, Financial interest; Beigene, Local PI, Institutional, Financial interest; Boehringer, Local PI, Institutional, Financial interest; FIBROGEN, Local PI, Institutional, Financial interest; IPSEN, Local PI, Institutional, Financial interest; IPSEN, Research Grant, Institutional, Financial interest; ITM, Local PI, Institutional, Financial interest; Merck, Research Grant, Institutional, Financial interest; MSD, Local PI, Institutional, Financial interest; NOVARTIS, Research Grant, Institutional, Financial interest; NUCANA, Local PI, Institutional, Financial interest. Non-Financial Interests: AIOM, Other, Internal reviewer of NET guidelines; ENETS, Member of Board of Directors; ESMO, Other, Member of the NET Faculty; SPARC Europe, Other, Steering committee. Francesco Panzuto: Advisor honoraria form Mylan (Viatris), Advanz pharma. Novartis, Camurus, Ipsen, Local PI, Institutional. Non-financial interest: AIOM, author of NET guidelines; ENETS, chair of the advisory board; Itanet, chief of the society]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Cardiovascular pathology is the main cause of death in chronic kidney disease (CKD) patients. CKD is associated with the accumulation of uremic toxins in the bloodstream, and indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of CKD patients. We conducted an in vitro study to assess the mechanisms underlying the IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We also studied their extracellular vesicles (EVs) owing to their capacity to act as messengers that transmit signals through their cargo., Main Methods: EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, flow cytometry, and tetraspanin expression. Cell lysates and isolated EVs were analyzed using liquid chromatography coupled with mass spectrometry, followed by Gene Set Enrichment Analysis to identify the altered pathways., Key Findings: Proteomic analysis of endothelial cells revealed that IS causes an increase in proteins related to adipogenesis, inflammation, and xenobiotic metabolism and a decrease in proliferation. Extracellular matrix elements, as well as proteins associated with myogenesis, response to UV irradiation, and inflammation, were found to be downregulated in IS-treated EVs. Fatty acid metabolism was also found to be increased along with adipogenesis and inflammation observed in cells., Significance: The treatment of endothelial cells with IS increased the expression of proteins related to adipogenesis, inflammation, and xenobiotic metabolism and was less associated with proliferation. Furthermore, EVs from cells treated with IS may mediate endothelial dysfunction, since they present fewer extracellular matrix elements, myogenesis, inflammatory factors, and proteins downregulated in response to UV radiation., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest related to the content of this article., (Copyright © 2024. Published by Elsevier Inc.)

Importance: The field of meniscal root preservation has undergone significant advancement over the past decades; however, the challenge remains to fully understand whether meniscal root repair can ultimately arrest or delay osteoarthritic changes., Objective: To assess longitudinal changes in articular cartilage, subchondral bone, and progression to meniscal extrusion (ME) using high-resolution magnetic resonance imaging (MRI)., Methods: Medial meniscus posterior root tear was surgically induced in 39 New Zealand white rabbits. Animals were randomly assigned into three experimental groups: partial meniscectomy after root tear (PM, n ​= ​13); root tear left in situ (CT, n ​= ​13); and transtibial root repair (RR, n ​= ​13). Contralateral limbs were used as healthy controls. High resolution 4.7 Tesla MRI of the knee joint was performed at baseline, after 2-, and 4-months of post-surgery. Cartilage thickness was calculated in medial and lateral compartments. In addition, the evaluation of ME, subchondral bone edema and healing potential after root repair were assessed too., Results: Progressive cartilage thinning, ME, and subchondral bone edema were evident in all 3 study groups after 4-months of follow-up. The mean cartilage thickness in the PM group was 0.53 ​mm (±0.050), 0.57 ​mm (±0.05) in the CT group, and 0.60 ​mm (±0.08) in the RR group. The PM group exhibited significantly higher cartilage loss when compared to the CT and RR groups (p ​< ​0.001). Moreover, progressive ME and subchondral bone edema were associated with a more severe cartilage loss at the final follow-up., Conclusion: Meniscal root repair did not halt but rather reduced the progression of osteoarthritis (OA). Degenerative changes worsened at a rapid rate in the PM group compared to the RR and CT groups. Early cartilage swelling, persistent subchondral edema, and progressive ME predicted a more severe progression to knee OA in the CT and RR groups., Level of Evidence: II., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Mycoplasma pneumoniae (M. pneumoniae) is a bacterium with particular characteristics that give rise to a broad clinical spectrum, being respiratory infection the most frequent presentation. Infection by M. pneumoniae occurs in cyclical epidemics, and paediatricians in Spain have noticed an increase in cases since January 2024, establishing hospital registers to collect surveillance data (as it is not a notifiable disease in Spain). The diagnosis of infection by M. pneumoniae is made through serological testing and/or the detection of genetic material by means of polymerase chain reaction (PCR). Neither methods can differentiate between colonization and active infection, so a precise diagnosis is not possible and testing should only be requested in the case of high clinical suspicion. The role of antibiotherapy in infection by M. pneumoniae in its different clinical variants is not well defined. Most infections are self-limiting and mild, and there is insufficient evidence to support the use of antibiotherapy in these cases. Antibiotic treatment is justified in patients with risk factors for the development of severe disease (Down syndrome, anatomical or functional asplenia, immunosuppression), in hospitalized patients with respiratory infection and in patients with moderate or severe extrapulmonary forms. Taking into account aspects concerning the rational use of antimicrobials, the treatment of choice would be clarithromycin, with azithromycin as an alternative, reserving the use of doxycycline and levofloxacin for cases of antimicrobial resistance and/or infections of the central nervous system., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery., Methods: MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov, NCT05059262, and enrolment is complete., Findings: Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group vs 0% (none of 40) in the placebo group (difference 40% [95% CI 29-51]; p<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted., Interpretation: Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients., Funding: Deciphera Pharmaceuticals., Competing Interests: Declaration of interests VB reports institutional research funding from Deciphera Pharmaceuticals and participation on a medical advisory board for Deciphera Pharmaceuticals. SS reports institutional research funding from Abbiski, Daiichi Sankyo, and Deciphera Pharmaceuticals, and advisory board roles with Daiichi Sankyo and Deciphera Pharmaceuticals. SB reports honoraria from Blueprint Medicine, Boehringer Ingelheim, Pfizer, PharmaMar, Uptodate, and Deciphera Pharmaceuticals; consulting or advisory roles with Adcendo, Bayer, Boehringer Ingelheim, Cogent Biosciences, Daiichi Sankyo, Lilly, IDRx, and Deciphera Pharmaceuticals; institutional research funding from Adcendo, Blueprint Medicine, Incyte, and IDRx; participation on a board for the University of Aachen; unpaid board of directors positions with The Connective Tissue Oncology Society and Deutsche Sarkomstiftung; and a faculty position with the European Society for Medical Oncology. AJW reports consulting or advisory roles and institutional research funding from Daiichi Sankyo and Deciphera Pharmaceuticals. MvdS reports travel partly supported by Deciphera Pharmaceuticals. NMB reports research support from Deciphera Pharmaceuticals. AAR reports consulting or advisory roles with Boehringer Ingelheim and Medison; institutional research funding from 23andMe, Abbisko, AbbVie, Adaptimmune, Amgen, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Inhibrx, Iterion Therapeutics, Karyopharm Therapeutics, MedImmune, Medison, Merck, Neoleukin Therapeutics, Pfizer, Rain Therapeutics, Roche/Genentech, Symphogen, and Deciphera Pharmaceuticals; and participation on an advisory board for Inhibrx. AI reports consulting or advisory roles for Bayer, Bristol Myers Squibb, Chugai Pharmaceutical, Merck, Merck Sharp & Dohme, Novartis, Parthenon, PharmaMar, and Roche; and institutional research funding from Bayer, Bristol Myers Squibb, Chugai Pharmaceutical, Merck, Merck Sharp & Dohme, Novartis, Parthenon, PharmaMar, and Roche. ALC reports honoraria from Bayer, PharmaMar, and Deciphera Pharmaceuticals. GT reports consulting or advisory roles with Daiichi Sankyo and Servier. KB reports honoraria from Incyte, Lilly, Novartis, and Deciphera Pharmaceuticals; expert testimony for Deciphera Pharmaceuticals; and advisory board participation for Bayer, GSK, and NEC OncoImmunity. JM-B reports consulting or advisory roles for Amgen, Asofarma, Boehringer Ingelheim, Bayer, GSK, Lilly, Novartis, PharmaMar, Roche, and Tecnofarma; speakers bureau involvement for PharmaMar; and institutional research funding from Adaptimmune, Amgen, Ayala Pharmaceuticals, Bayer, Blueprint Medicines, Bristol Myers Squibb, Cebiotex, Celgene, Daiichi Sankyo, Eisai, GSK, IMMIX Biopharma, Inhibrx, Karyopharm Therapeutics, Lilly, Lixte, Novartis, Pfizer, PharmaMar, Philogen, PTC Therapeutics, Rain Therapeutics, and Deciphera Pharmaceuticals; expert testimony for Amgen, Bayer, Boehringer Ingelheim, Eisai, Lilly, PharmaMar, and Roche; travel support from Novartis, Pfizer, and PharMar; advisory board participation for Asofarma and Tecnofarma; and a leadership or fiduciary role for Sarcoma Research solutions. EP reports advisory board roles with Daiichi Sankyo, SynOx, and Deciphera Pharmaceuticals. PRe reports honoraria for participation in advisory boards for Bayer, Blueprint Medicines, Boehringer Ingelheim, Clinigen, GSK, MundiBioPharma, Novartis, PharmaMar, Roche, and Deciphera Pharmaceuticals, and a leadership position for the German Sarcoma Foundation. PRu reports honoraria from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, and Sanofi; speakers bureaus for Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, and Pierre Fabre; travel support from Orphan Europe and Pierre Fabre; consulting fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Philogen, and Pierre Fabre; and institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and Roche. CT, FZ, and BH report employment with and stock or other ownership interests in Deciphera Pharmaceuticals. MGS reports employment with, stock or other ownership interests in, and travel support from Deciphera Pharmaceuticals. RR-S reports employment with, stock or other ownership interests in, and patents, royalties, or other intellectual property from Deciphera Pharmaceuticals (inventor in pending patents at Deciphera Pharmaceuticals for which the rights have been transferred to Deciphera Pharmaceuticals; RR-S has not received and will not receive any royalties). MLS reports employment in a leadership role with, stock or other ownership interests in, travel support from, and patents, royalties, or other intellectual property from Deciphera Pharmaceuticals (inventor in pending patents at Deciphera Pharmaceuticals for which the rights have been transferred to Deciphera Pharmaceuticals; MLS has not received and will not receive any royalties). J-YB reports honoraria from Bayer and Deciphera Pharmaceuticals; consulting or advisory roles with Bayer and Deciphera Pharmaceuticals; institutional research funding from Bayer and Deciphera Pharmaceuticals; academic support from the French National Cancer Institute (INCA) NETSARC, INTERSARC, and EURACAN; and funding for travel, accommodation, or expenses from OSE Pharma. WDT reports advisory board roles for Aadi Biosciences, Abbisko, Amgen, AmMax Bio, Avacta, Bayer, BioAtla, Boehringer Ingelheim, C4 Therapeutics, Cogent Biosciences, Daiichi Sankyo, Foghorn Therapeutics, IMGT, Inhibrx, Ipsen, Lilly, PharmaEssentia, Servier, Sonata, and Deciphera Pharmaceuticals; owns stock or shares in Atropos and Certis Oncology Solutions; reports a patent for Companion Diagnostics for CDK4 inhibitors (14/854,329) and for Enigma and CDH18 (SKI2016–021–03); and reports institutional funding from Deciphera Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial extension. IT therapies aim to effect tumor regression by directly injecting antineoplastic agents into lesions. However, there is a lack of updated evidence regarding IT therapies in HNSCC., Patients and Methods: A systematic literature search (CRD42023462291) was conducted using WebOfScience, ClinicalTrials.gov, and conference abstracts from ESMO and ASCO, identifying for IT clinical trials in patients with HNSCC, from database creation to September 12th, 2023. Efficacy as well as safety (grade ≥ 3 treatment-related adverse events[trAEs]) were reported., Results: After evaluation of 1180 articles identified by the systematic search, 31 studies treating 948 patients were included. IT injectables were categorized as chemotherapies with or without electroporation (k = 4, N = 268), oncolytic viruses, plasmids, and bacteria-based (k = 16, N = 446), immunotherapies and EGFR-based therapies (k = 5, N = 160), radioenhancer particles (k = 2, N = 68), and calcium electroporation (k = 1, n = 6). EGFR-antisense plasmids, NBTXR3 radioenhancer and immune innate agonists show best overall response rates, at 83 %, 81 % and 44 % respectively. Eleven (35 %) studies added systemic therapy or radiotherapy to the IT injections. No study used predictive biomarkers to guide patient selection. 97 % studies were phase I-II. Safety-wise, electroporation and epinephrine-based injectable trials had significant local symptoms such as necrosis, fistula formation and post-injection dysphagia. Treatment-related tumor haemorrhages of various grades were described in several trials. Grade ≥ 3 trAEs attributable to the other therapies mainly comprised general symptoms such as fatigue. There were 3 injectable-related deaths across the systematic review., Conclusion: This is the first review to summarize all available evidence of IT in HNSCC. As of today, IT therapies lack sufficient evidence to recommend their use in clinical practice. Continuing research on potential molecules, patient selection, safe administration of injections and controlled randomized trials are needed to assess their added benefit., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PJL: research funding from Roche, Merck; speakerś bureau from MSD Merck Sharp & Dohme, travel and accommodation expenses from MSD, and Novartis; and stockholding from Elli Lilly outside the current work. AHC: travel and accommodation expenses from Merck Serono and Kyowa Kirin International and research grant from Gilead (Inst) outside the current work. IB received personal fees from Merck sharp & Dohme, Sanofi, Achilles Therapeutics, eTheRNA Immunotherapies, Cancer Expert Now, Boehringer Ingelheim as a Speakers’ Bureau: Bristol Myers Squibb, Merck Serono, Roche, MSD. Lastly, as a research Funding: AstraZeneca (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Gliknik (Inst), GlaxoSmithKline (Inst), Janssen Oncology (Inst), Kura Oncology (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), Pfizer (Inst), Roche (Inst), Shattuck labs (Inst), Nanobiotix (Inst), Seattle Genetics (Inst), Immutep (Inst), Debiopharm Group (Inst), Regeneron (Inst), Boehringer Ingelheim (Inst), ISA Pharmaceuticals (Inst), Merck Serono (Inst), Seattle Genetics (Inst), Northern Biologics (Inst), VCN Biosciences (Inst), and for travel, accommodations and expenses: MSD Oncology. VM: Consulting or Advisory Role: Roche (Inst), Bayer (Inst), Pieris (Inst), BMS (Inst), Janssen (Inst), Basilea (Inst), Regeneron/Sanofi (Inst), BMS (Inst), Bayer (Inst), Nanobiotix (Inst). Research Funding: AbbVie (Inst), Achilles (Inst), AbbVie (Inst), AceaBio (Inst), Adaptimmune (Inst), ADC Therapeutics (Inst), Arcus (Inst), Ascendis Pharma (Inst), Aduro (Inst), Agenus (Inst), Amcure (Inst), Amgen (Inst), Astellas (Inst), AstraZeneca (Inst), Bayer (Inst), Beigene (Inst), Biomea (Inst), BioInvent International AB (Inst), BMS (Inst), Boehringer (Inst), Boston Therapeutics (Inst), Celgene (Inst), Daiichi Sankyo (Inst), Debiopharm (Inst), Eisai (Inst), e-Terapeutics (Inst), Exelixis (Inst), Forma Therapeutics (Inst), Genmab (Inst), GSK (Inst), Harpoon (Inst), Hutchison (Inst), Immutep (Inst), Incyte (Inst), Inovio (Inst), Iovance (Inst), Janssen (Inst), Kyowa Kirin (Inst), Lilly (Inst), Loxo (Inst), Monta Bioscience (Inst), MedSir (Inst), Menarini (Inst), Merck (Inst), Merus (Inst), Millennium (Inst), MSD (Inst), Nanobiotix (Inst), Nektar (Inst), Novartis (Inst), Odonate Therapeutics (Inst), Pfizer (Inst), Pharma Mar (Inst), PharmaMar (Inst), Principia (Inst), PsiOxus (Inst), Puma (Inst), Regeneron (Inst), Relay Therapeutics (Inst), Revolution Medicines (Inst), Rigontec (Inst), Roche (Inst), Sanofi (Inst), Sierra Oncology (Inst), Synthon (Inst), Taiho (Inst), Takeda (Inst), Tesaro (Inst), Transgene (Inst), Turning Point Therapeutics (Inst), Upsher-Smith (Inst). BD: Principal Investigator – Institutional Funding: AbbVie, Achilles, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Arcus, Ascendis Pharma, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer, Beigene, Biomea, BioInvent International AB, BMS, Boheringer, Boston Therapeutics, Celgene, Daichii Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, Monta Bioscience, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Relay Therapeutics, Revolution Medicines, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith. KJH received honoraria from Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys Biopharma (Inst), Pfizer (Inst), Replimune (Inst), Inzen Therapeutics (Inst) and Codiak Biosciences (Inst). Consulting or Advisory Role: Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys BioPharma (Inst), Replimune (Inst), Inzen Therapeutics (Inst) Speakers’ Bureau: BMS (Inst), Merck Serono (Inst), MSD (Inst) Research Funding: AstraZeneca (Inst), Merck Sharp & Dohme (Inst), Replimune (Inst), Boehringer Ingelheim (Inst). All other authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Context: Music listening (ML) has been shown to have a beneficial effect on patients with cancer. However, novel intervention approaches are needed., Objectives: We aimed to determine whether ML based on the iso-principle, conducted using a mobile application (GloMus), improves symptom burden, quality of life (QoL), anxiety, and depression in patients undergoing stem cell transplantation (SCT) and intensive induction chemotherapy for acute myeloid leukemia (AML)., Methods: In this randomized controlled clinical trial, we assigned 71 patients to the ML or standard care (SC) groups, stratified by the reason for admission (AML, allogeneic-SCT, or inpatient/outpatient autologous-SCT). Upon admission, participants in the ML groups were invited to undergo daily ML sessions designed to change negative moods into positive ones (iso-principle). The intervention consisted of listening to pre-recorded classical music ordered by beats per minute and tonality. Symptom burden (Edmonton Symptom Assessment System-Revised) was assessed in the ML groups before and after each session. Anxiety, depression (Hospital Anxiety and Depression Scale), and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation/Leukemia) were measured weekly in the ML and SC groups., Results: Symptom burden in both allogeneic- and inpatient autologous-SCT ML groups reduced after the intervention. In all experimental groups, clinically important improvements were observed after ML sessions. No differences were found between the groups (ML vs. SC) at different weeks of admission regarding anxiety, depression, and QoL., Conclusions: ML based on our innovative iso-principle strategy, conducted using GloMus, reduced the symptom burden in patients undergoing allogeneic- and inpatient autologous-SCT (ClinicalTrials.gov number, NCT05696457)., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis., Methods: The abatacept reversing subclinical inflammation as measured by MRI in ACPA positive arthralgia (ARIAA) study is a randomised, international, multicentre, double-blind, placebo-controlled trial done in 14 hospitals and community centres across Europe (11 in Germany, two in Spain, and one in the Czech Republic). Adults (aged ≥18 years) with ACPA positivity, joint pain (but no swelling), and signs of osteitis, synovitis, or tenosynovitis in hand MRI were randomly assigned (1:1) to weekly subcutaneous abatacept 125 mg or placebo for 6 months followed by a double-blind, drug-free, observation phase for 12 months. The primary outcome was the proportion of participants with any reduction in inflammatory MRI lesions at 6 months. The primary efficacy analysis was done in the modified intention-to-treat population, which included participants who were randomly assigned and received study medication. Safety analyses were conducted in participants who received the study medication and had at least one post-baseline observation. The study was registered with the EUDRA-CT (2014-000555-93)., Findings: Between Nov 6, 2014, and June 15, 2021, 139 participants were screened. Of 100 participants, 50 were randomly assigned to abatacept 125 mg and 50 to placebo. Two participants (one from each group) were excluded due to administration failure or refusing treatment; thus, 98 were included in the modified intention-to-treat population. 70 (71%) of 98 participants were female and 28 (29%) of 98 were male. At 6 months, 28 (57%) of 49 participants in the abatacept group and 15 (31%) of 49 participants in the placebo group showed improvement in MRI subclinical inflammation (absolute difference 26·5%, 95% CI 5·9-45·6; p=0·014). Four (8%) of 49 participants in the abatacept group and 17 (35%) of 49 participants in the placebo group developed rheumatoid arthritis (hazard ratio [HR] 0·14 [0·04-0·47]; p=0·0016). Improvement of MRI inflammation (25 [51%] of 49 participants in the abatacept group, 12 [24%] of 49 in the placebo group; p=0·012) and progression to rheumatoid arthritis (17 [35%] of 49, 28 [57%] of 49; HR 0·14 [0·04-0·47]; p=0·018) remained significantly different between the two groups after 18 months, 12 months after the end of the intervention. There were 12 serious adverse events in 11 participants (four [8%] of 48 in the abatacept group and 7 [14%] of 49 in the placebo group). No deaths occurred during the study., Interpretation: 6-month treatment with abatacept decreases MRI inflammation, clinical symptoms, and risk of rheumatoid arthritis development in participants at high risk. The effects of the intervention persist through a 1-year drug-free observation phase., Funding: Innovative Medicine Initiative., Competing Interests: Declaration of interests JR reports receiving an unrestricted research grant from Sobi and Novartis, and speakers' honoraria and consulting fees from Bristol-Myers Squibb, Novartis, and Sobi. KT reports receiving speakers' honoraria and consulting fees from Novartis and Union Chimique Belge, and travel support from Celltrion. MØ reports receiving grants from AbbVie, Bristol-Myers Squibb, Merck, Novartis, and Union Chimique Belge, consulting fees from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and Union Chimique Belge, and honoraria for lectures, presentations, and speakers' bureaus from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and Union Chimique Belge. AK reports receiving honoraria for lectures and presentations, honoraria for participation on a data safety monitoring board (IIT TOLERA study), and honoraria for drug supply (IIT TOLERA study) from Bristol-Myers Squibb. BM reports receiving honoraria for lectures from Gilead, AbbVie, Janssen, and Pfizer. AJH reports receiving payment for a conditional grant from Galapagos and Novartis, consulting fees from AbbVie, Amgen, Galapagos, Janssen, Eli Lilly, Novartis, and Union Chimique Belge, and payment for lectures and presentations from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Eli Lilly, Medupdate, Novartis, Pfizer, Rheumaakademie, and Union Chimique Belge. XB reports receiving consulting fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Union Chimique Belge, honoraria for lectures and presentations from AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Union Chimique Belge, and payment for participation on a data safety monitoring board or an advisory board from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Union Chimique Belge. MFl reports receiving honoraria for presentations and lectures from AbbVie, Actelion, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Janssen, Medac, Menarini, Merck Sharp & Dohme, Novartis, Pfizer, Rheumaakademie, Roche, and Sobi. AR-R reports receiving consulting fees from Bristol-Myers Squibb, AbbVie, Pfizer, and Eli Lilly, payment for lectures and presentations from AbbVie, Bristol-Myers Squibb, Pfizer, Galapagos, Eli Lilly, Merck Sharp & Dohme, Union Chimique Belge, Sanofi, and Roche, payment for expert testimony from AbbVie and Galapagos, support for attending meetings or travel (or both) from Pfizer and Sanofi, participating on a data safety monitoring board for R-Pharm, and having a leadership or fiduciary role in the Swiss Rheumatology Society. RV reports receiving payment for lectures and presentations from AbbVie, AstraZeneca, Galapagos, GlaxoSmithKline, Novartis, Janssen–Cilag, and Pfizer, institutional support for attending meetings or travel (or both) from AbbVie, Galapagos, and Janssen–Cilag, institutional grants from Novartis and Pfizer, and participating on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Novartis, GlaxoSmithKline, and Union Chimique Belge. NV reports receiving honoraria for lectures and presentations and support for attending scientific meetings and congresses (congress fee and travel expenses) from Bristol-Myers Squibb. JT reports receiving an unrestricted research grant from Bristol-Myers Squibb, consulting fees from AbbVie, AstraZeneca, Novartis, GlaxoSmithKline, Eli Lilly, and Vifor, support for attending a meeting from Galapagos and Bristol-Myers Squibb, and participating on an advisory board for Novartis. EF reports receiving honoraria for lectures and presentations from AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Sobi, support for attending meetings from Novartis, and institutional grants from Eli Lilly, Novartis, and Galapagos. KK reports receiving honoraria from Union Chimique Belge for participation in an advisory board and reports payment for presentations from AbbVie, Novartis, and Union Chimique Belge. JS reports receiving honoraria for lectures and presentations from AbbVie, Bristol-Myers Squibb, Union Chimique Belge, Pfizer, Novartis, and Amgen, support for attending meetings from Union Chimique Belge and Janssen, and participating on an advisory board from AbbVie, Novartis, and Union Chimique Belge. EN reports receiving institutional payment from Pfizer and Eli Lilly, and payment for lecturing from AbbVie, Pfizer, and Eli Lilly. GS reports receiving speakers' honoraria and consulting fees from Bristol-Myers Squibb, Cabaletta, Janssen, Kyverna, Miltenyi, and Novartis. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Genetic diagnosis of inherited platelet disorders (IPDs) is mainly performed by high-throughput sequencing (HTS). These short-read-based sequencing methods sometimes fail to characterize the genetics of the disease., Objectives: To evaluate nanopore long-read DNA sequencing for characterization of structural variants (SVs) in patients with IPDs., Methods: Four patients with a clinical and laboratory diagnosis of Glanzmann thrombasthenia (GT) (P1 and P2) and Hermansky-Pudlak syndrome (HPS) (P3 and P4) in whom HTS missed the underlying molecular cause were included. DNA was analyzed by both standard HTS and nanopore sequencing on a MinION device (Oxford Nanopore Technologies) after enrichment of DNA spanning regions covering GT and HPS genes., Results: In patients with GT, HTS identified only 1 heterozygous ITGB3 splice variant c.2301+1G>C in P2. In patients with HPS, a homozygous deletion in HPS5 was suspected in P3, and 2 heterozygous HPS3 variants, c.2464C>T (p.Arg822∗) and a deletion affecting 2 exons, were reported in P4. Nanopore sequencing revealed a complex SV affecting exons 2 to 6 in ITGB3 (deletion-inversion-duplication) in homozygosity in P1 and compound heterozygosity with the splice variant in P2. In the 2 patients with HPS, nanopore defined the length of the SVs, which were characterized at nucleotide resolution. This allowed the identification of repetitive Alu elements at the breakpoints and the design of specific polymerase chain reactions for family screening., Conclusion: The nanopore technology overcomes the limitations of standard short-read sequencing techniques in SV characterization. Using nanopore, we characterized novel defects in ITGB3, HPS5, and HPS3, highlighting the utility of long-read sequencing as an additional diagnostic tool in IPDs., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation., Methods: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H 2 O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H 2 O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete., Findings: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients., Interpretation: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation., Funding: Instituto de Salud Carlos III and the European Regional Development Funds., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project., Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m 2 ; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease., Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P  < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) ( P  = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P  = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P  < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P  < 0.05). These vascular changes were independent of differences in age., Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health., (© 2024 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Gene therapy has become a clinical reality as market-approved advanced therapy medicinal products for the treatment of distinct monogenetic diseases and B-cell malignancies. This Therapeutic Review aims to explain how progress in genome editing technologies offers the possibility to expand both therapeutic options and the types of diseases that will become treatable. To frame these impressive advances in the context of modern medicine, we incorporate examples from human clinical trials into our discussion on how genome editing will complement currently available strategies in gene therapy, which still mainly rely on gene addition strategies. Furthermore, safety considerations and ethical implications, including the issue of accessibility, are addressed as these crucial parameters will define the impact that gene therapy in general and genome editing in particular will have on how we treat patients in the near future., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background Aims: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC., Methods: We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells., Results: Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells., Conclusions: Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

This paper reports on a comprehensive approach to characterize a set of kidney stones through various analytical techniques including ESEM-EDS, XRD, Raman, and CL spectroscopy, linked to an assessment of the patient's lifestyle and dietary habits. The use of these techniques can provide valuable insights into the underlying causes of stone formation and guide strategies for prevention and treatment. ESEM-EDS and XRD are commonly used techniques for kidney stone characterization due to their complementary nature, enabling the identification of a wide range of renal calculi. However, these techniques may not be sensitive enough to determine the detailed composition of the samples. In such cases, Raman and CL techniques can be used to provide more precise information about the chemical and structural composition of the stones. Raman spectroscopy, for example, can identify molecular phases observed under an optical microscope characterizing chemical compositions through vibrational modes associated with specific bonds. The CL spectral emission within the 250-850 nm range can also yield valuable information about the mineral phases, including the identification of structural crystallinity, hydrated molecules, Ca-OH bonds, and oxygen defects. By correlating spectral analyses with patient habits, this study identifies potential exogenous factors contributing to stone formation, including excess protein consumption, urinary bacterial infections, and oxalate-rich diets. This comprehensive approach provides a more complete understanding of the composition of kidney stones helping to personalized prevention and treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cholangiocarcinomas (CCA) are a heterogeneous group of tumors that are classified as intrahepatic, perihilar, or distal according to the anatomic location within the biliary tract. Each CCA subtype is associated with distinct genomic alterations, including single nucleotide variants, copy number variants, and chromosomal rearrangements or gene fusions, each of which can influence disease prognosis and/or treatment outcomes. Molecular profiling using next-generation sequencing (NGS) is a powerful technique for identifying unique gene variants carried by an individual tumor, which can facilitate their accurate diagnosis as well as promote the optimal selection of gene variant-matched targeted treatments. NGS is particularly useful in patients with CCA because between one-third and one-half of these patients have genomic alterations that can be targeted by drugs that are either approved or in clinical development. NGS can also provide information about disease evolution and secondary resistance alterations that can develop during targeted therapy, and thus facilitate assessment of prognosis and choice of alternative targeted treatments. Pathologists play a critical role in assessing the viability of biopsy samples for NGS, and advising treating clinicians whether NGS can be performed and which of the available platforms should be used to optimize testing outcomes. This review aims to provide clinical pathologists and other healthcare professionals with practical step-by-step guidance on the use of NGS for molecular profiling of patients with CCA, with respect to tumor biopsy techniques, pre-analytic sample preparation, selecting the appropriate NGS panel, and understanding and interpreting results of the NGS test., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: Albrecht Stenzinger: Consulting or advisory role: AGCT, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly and Company, Illumina, Janssen, Novartis, Seagen, Takeda, ThermoFisher Scientific. Speaker’s bureau: AstraZeneca, Bayer, Bristol Myers Squibb, Illumina, MSD, Novartis, Roche, ThermoFisher Scientific. Research funding: Bayer, Bristol Myers Squibb, Chugai, Incyte. Arndt Vogel: Speaker, consulting, and advisory role: AstraZeneca, Bayer, Bristol Myers Squibb, BTG, Daiichi Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Imaging Equipment Ltd (AAA), Incyte, Ipsen, Merck, MSD, Pierre Fabre, Roche, Sanofi, Servier, Sirtex, Terumo. Ulrich Lehmann: Speaker and advisory role: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Novartis, Roche, Servier. Angela Lamarca: Travel and educational support: AAA, Bayer, Delcath Pharma, Ipsen, Mylan, Novartis, Pfizer, Roche, Sirtex. Speaker honoraria: AAA, Advanz Pharma, AstraZeneca, Eisai, Incyte, Ipsen, Merck, Pfizer, QED, Roche, Servier. Advisory and consulting honoraria: Albireo Pharma, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Eisai, GENFIT, Ipsen, Nutricia, QED, Roche, Servier, Taiho, TransThera Biosciences. Research funding (to institution): Albireo Pharma, AstraZeneca, Boehringer Ingelheim, GENFIT, Merck, Servier. Member of the Knowledge Network and NetConnect Initiatives, funded by Ipsen. Paul Hofman: Consulting or advisory role: AbbVie, Amgen, AstraZeneca, Biocartis, Bristol Myers Squibb, Eli Lilly and Company, Guardant Health, Janssen, Novartis, Pfizer, QIAGEN, Roche. Research funding (to institution): Amgen, AstraZeneca, Biocartis, Bristol Myers Squibb, Roche, ThermoFisher Scientific. Luigi Terracciano: Advisory and consulting honoraria: Amgen, AstraZeneca, Janssen, Merck, Novartis, Roche, ThermoFisher Scientific. Nicola Normanno: Speaker’s bureau and/or advisory boards: AstraZeneca, Bayer, Biocartis, Bristol Myers Squibb, Eli Lilly and Company, Illumina, Incyte, Merck, MSD, Novartis, Roche, Sanofi, ThermoFisher. Research funding (to institution): AstraZeneca, Biocartis, Illumina, Merck, QIAGEN, Roche, SOPHiA Genetics, ThermoFisher., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Precision medicine is a major achievement that has impacted on management of patients diagnosed with advanced cholangiocarcinoma (CCA) over the last decade. Molecular profiling of CCA has identified targetable alterations, such as fibroblast growth factor receptor-2 (FGFR-2) fusions, and has thus led to the development of a wide spectrum of compounds. Despite favourable response rates, especially with the latest generation FGFRi, there are still a proportion of patients who will not achieve a radiological response to treatment, or who will have disease progression as the best response. In addition, for patients who do respond to treatment, secondary resistance frequently develops and mechanisms of such resistance are not fully understood. This review will summarise the current state of development of FGFR inhibitors in CCA, their mechanism of action, activity, and the hypothesised mechanisms of resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Acromioclavicular joint (ACJ) stabilizations are associated with a high overall failure rate with 9.5% of these patients requiring subsequent revision surgery. Consequently, understanding the specific cause of primary ACJ stabilization failure is paramount to improving surgical decision-making in this challenging patient cohort., Purpose: To (1) identify risk factors and mechanisms for failure following primary arthroscopically-assisted ACJ stabilization to highlight the importance of conducting a detailed failure analysis and to (2) establish revision strategies based on real-life cases of primary failed ACJ stabilization., Study Design: Level of evidence IV., Methods: A survey was shared internationally among members of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) shoulder committee. The survey contained failure analysis of 11 real-life cases of failed primary arthroscopically-assisted ACJ stabilization. For each case, a thorough patient history, standardized radiographs, and CT scans were provided. Participants were asked to give their opinion on bone tunnel placement, cause of failure (biological, technical, traumatic, or combined), the stabilization technique used, as well as give a recommendation for revision., Results: Seventeen members of the ISAKOS shoulder committee completed the survey. Biological failure was considered the most common cause of failure (47.1%), followed by technical (35.3%) and traumatic (17.6%) failure. The majority deemed two modifiable factors (i.e., patient's profession and sport) as well as non-modifiable factors (i.e., patient's age and time from trauma to initial surgery) to be risk factors for failure. In 10 of 11 cases, the correct fixation device was used in the primary setting (90.9%; 52.8-82.4% agreement); however, in eight of those cases, the technique was not performed correctly (80.0%; 58.8-100% agreement). In 8 of all 11 cases, the majority recommended an arthroscopically assisted technique with graft augmentation for revision (52.9-58.8% agreement)., Conclusion: Biological failure and technical failure are the most common reason for failure in primary ACJ stabilization followed by traumatic failure. Besides, biological failure can be triggered by technical errors such as clavicular or coracoidal tunnel misplacement. Consequently, a detailed failure analysis including preoperative CT should be conducted on the causes of primary ACJ failure, and, if possible, an arthroscopically-assisted technique with graft augmentation should be prioritized in revision ACJ surgery., Clinical Relevance: ACJ stabilizations are associated with a high overall failure rate - potentially due to biological and technical properties. When encountering failed arthroscopically-assisted ACJ stabilization, a detailed failure analysis should be conducted on the causes of primary ACJ failure. Furthermore, an arthroscopically-assisted revision stabilization is feasible in most cases., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Peripheral arterial disease (PAD) is a leading cause of morbimortality worldwide. Lipocalin-2 (LCN2) has been associated with higher risk of amputation or mortality in PAD and might be involved in muscle regeneration. Our aim is to unravel the role of LCN2 in skeletal muscle repair and PAD., Methods and Results: WT and Lcn2 -/- mice underwent hindlimb ischemia. Blood and crural muscles were analyzed at the inflammatory and regenerative phases. At day 2, Lcn2 -/- male mice, but not females, showed increased blood and soleus muscle neutrophils, and elevated circulating pro-inflammatory monocytes (p < 0.05), while locally, total infiltrating macrophages were reduced (p < 0.05). Moreover, Lcn2 -/- soleus displayed an elevation of Cxcl1 (p < 0.001), and Cxcr2 (p < 0.01 in males), and a decrease in Ccl5 (p < 0.05). At day 15, Lcn2 deficiency delayed muscle recovery, with higher density of regenerating myocytes (p < 0.04) and arterioles (αSMA + , p < 0.025). Reverse target prediction analysis identified miR-138-5p as a potential regulator of LCN2, showing an inverse correlation with Lcn2 mRNA in skeletal muscles (rho = -0.58, p < 0.01). In vitro, miR-138-5p mimic reduced Lcn2 expression and luciferase activity in murine macrophages (p < 0.05). Finally, in human serum miR-138-5p was inversely correlated with LCN2 (p ≤ 0.001 adjusted, n = 318), and associated with PAD (Odds ratio 0.634, p = 0.02, adjusted, PAD n = 264, control n = 54)., Conclusions: This study suggests a possible dual role of LCN2 in acute and chronic conditions, with a probable role in restraining inflammation early after skeletal muscle ischemia, while being associated with vascular damage in PAD, and identifies miR-138-5p as one potential post-transcriptional regulator of LCN2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection during follow-up compared with controls with a negative SFC., Methods: This retrospective multicentre observational study was performed within the European Study Group of Implant-Associated Infections. All patients who underwent revision surgery of a prosthetic joint between 2013 and 2019 and had a minimum follow-up of 1 year were included. Patients with positive tissue cultures or synovial fluid cultures were excluded from the study., Results: A total of 95 cases (positive SFC) and 201 controls (negative SFC) were included. Infection during follow-up occurred in 12 of 95 cases (12.6%) versus 14 of 201 controls (7.0%) (p = 0.125). In all, 79.8% of cases were with treated with antibiotics (76/95). Of the non-treated cases, 89% (17/19) had a positive SFC with a low virulent microorganism. When solely analysing patients who were not treated with antibiotics, 16% of the cases (3/19) had an infection during follow-up versus 5% of the controls (9/173) (p = 0.08)., Discussion: Although not statistically significant, infections were almost twice as frequent in patients with an isolated positive SFC. These findings require further exploration in larger trials and to conclude about the potential benefit of antibiotic treatment in these cases., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance against nuclear and cytoplasmic self-antigens, induction of immunity and tissue inflammation. Lupus nephritis (LN), the most important predictor of morbidity in SLE, develops in almost 30% of SLE patients at disease onset and in up to 50-60% within the first 10 years. Firstly, in this review, we put the pathogenic mechanisms of the disease into a conceptual frame, giving emphasis to the role of the innate immune system in this loss of self-tolerance and the induction of the adaptive immune response. In this aspect, many mechanisms have been described such as dysregulation and acceleration of cell-death pathways, an aberrant clearance and overload of immunogenic acid-nucleic-containing debris and IC, and the involvement of antigen-presenting cells and other innate immune cells in the induction of this adaptive immune response. This result in a clonal expansion of autoreactive lymphocytes with generation of effector T-cells, memory B-cells and plasma cells that produce autoantibodies that will cause kidney damage. Secondly, we review the immunological pathways of damage in the kidney parenchyma, initiated by autoantibody binding and immune complex deposition, and followed by complement-mediated microvascular injury, activation of kidney stromal cells and the recruitment of leukocytes. Finally, we summarize the rationale for the treatment of LN, from conventional to new targeted therapies, focusing on their systemic immunologic effects and the minimization of podocytary damage., Competing Interests: Declaration of Competing Interest MX received lecture fees from GSK. JGP discloses honoraria from AstraZeneca, Abbvie, Galápagos, GSK, Janssen, ElyLilly, Pfizer, and Advisory for Galapagos and Sanofi. RC discloses honoraria and advisory from AstraZeneca, Celgene, GSK, Janssen, ElyLilly, Pfizer, UCB and Rubió. AK discloses consulting from CSL Vifor, Otsuka, Catalyst Biosciences, Walden Biosciences, GSK and Delta4. DJ received consultancy fees from Astra-Zeneca, BMS, Boehringer-Ingelheim, Chemocentryx, GSK, NICE, Novartis, Otsuka, Roche/Genentech, Takeda, UCB&Vifor; lecture fees from Amgen, Kessai, Vifor; and has stock options from Aurinia. Also, he received research grants from GSK, Roche/Genentech, EU, MRC, NIHR, Versus Arthritis. HJA received consultancy and lecture fees from Otsuka, GSK, Novartis, Janssen, AstraZeneca, Roche, and Vifor. FH received grants from GSK and Roche. GE received research funding from GSK and payments for presentations and advice from GSK and Otsuka. LFQ received honoraria from GSK, Otsuka, CSL Vifor and is on the advisory board of GSK, Otsuka, Alexion, Novartis and CSL Vifor. GMLL, FT, AE, CS, JR and AGH have nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain., Objectives: To provide recommendations for the administration of nirsevimab for prevention of RSV disease., Methods: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions., Results: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis., Conclusions: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis., (Copyright © 2023 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)