Variable treatment response to lumasiran in pediatric patients with primary hyperoxaluria type 1.

Background: Primary hyperoxaluria type 1 (PH 1) is a rare genetic condition due to mutations in the AGXT gene. This leads to an overproduction of oxalate in the liver. Hyperoxaluria often causes kidney stones, nephrocalcinosis, and chronic kidney disease.

Low-Level Tragus Stimulation as a treatment for primary hypertension - a systemic reaction with a broader cardioprotective potential?

Low-Level Tragus Stimulation [LL-TS] as a non-invasive technique of vagus nerve stimulation [VNS] moves to the fore in autonomic nervous system [ANS] studies as a non-drug based, easy applicable tool. LL-TS triggering a complex systemic response may offer a broader cardioprotective potential than expected as a recent investigation outlined blood pressure [BP] reduction by LL-TS in patients with hypertension which is commonly related to imbalance of the ANS as several other cardiovascular diseases.

The Focal Induction of Reactive Oxygen Species in Rats as a Trigger of Aortic Valve Degeneration.

Background: Degenerative aortic valve disease (DAVD) is a multifactorial process. We developed an animal model to analyze the isolated, local effect of reactive oxygen species (ROS) on its pathophysiology.

Methods: We utilized a photodynamic reaction (PDR) as a source of ROS in the aortic valve by aiming a laser at the aortic valve for 60 min after the administration of a photosensitizer 24 h prior.

Interleukin 1 β suppresses bile acid-induced BSEP expression via a CXCR2-dependent feedback mechanism.

Inflammation-induced cholestasis is a common problem in septic patients and results from cytokine-mediated inhibition of bile acid export including impaired expression of the bile salt export pump (BSEP) with a consecutive increase in intracellular bile acids mediating cell damage. The present study focuses on the mechanisms by which interleukin 1 β (IL-1β), as a critical mediator of sepsis-induced cholestasis, controls the expression of BSEP in hepatocytes. Notably, the treatment of hepatocytes with IL-1β leads to the upregulation of a broad chemokine pattern.

Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047.

Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not statistically significant improvement in overall survival (OS) and a numerically higher objective response rate (ORR) compared with nivolumab in the RELATIVITY-047 trial (ClinicalTrials.gov identifier: NCT03470922). We report updated descriptive efficacy and safety results from RELATIVITY-047 with a median follow-up of 33.

Childhood interstitial lung disease survivors in adulthood: a European collaborative study.

Background: Interstitial lung disease (ILD) is rarer in children (chILD) than adults, but with increasing diagnostic awareness, more cases are being discovered. chILD prognosis is often poor, but increasing numbers are now surviving into adulthood.

Aim: To characterize chILD-survivors and identify their impact on adult-ILD centers.

Evidentiary basis of the first regulatory qualification of a digital primary efficacy endpoint.

Stride velocity 95th centile (SV95C) is a wearable-derived endpoint representing the 5% fastest strides taken during everyday living. In July 2023, SV95C received European Medicines Agency (EMA) qualification for use as a primary endpoint in trials of patients with Duchenne muscular dystrophy (DMD) aged ≥ 4 years-becoming the first digital endpoint to receive such qualification. We present the data supporting this qualification, providing insights into the evidentiary basis of qualification as a digital clinical outcome assessment.

Benefit-risk assessment based on number needed to treat and number needed to harm: Atogepant vs. calcitonin gene-related peptide monoclonal antibodies.

Background: To evaluate the benefit-risk assessment of atogepant and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population.

Methods: The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks.

Durable left ventricular assist devices following temporary circulatory support on a microaxial flow pump with and without extracorporeal life support.

Background: Circulatory support with a catheter-based microaxial flow pump (mAFP) plays a major role in the treatment of severe cardiogenic shock. In most patients who fail to recover while on temporary mechanical circulatory support (tMCS) and who are not eligible for heart transplantation, durable left ventricular assist device (dLVAD) implantation is usually considered a reliable option. This study aimed to describe the outcome of dLVAD therapy following mAFP support and to identify predictors of mortality.

Ultrasound analysis of different forms of hemolytic uremic syndrome in children.

Background: Hemolytic uremic syndrome (HUS) is the most common cause of acute kidney injury in children. It is mainly caused by Shiga toxin-producing enterohemorrhagic (EHEC; STEC-HUS) and is more rarely caused by uncontrolled complement activation (cHUS). Renal replacement therapy is frequently required and kidney function recovers in the majority of patients.

275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management, 9-11 February 2024, Hoofddorp, the Netherlands.

The 275th ENMC workshop on the diagnosis and management of seronegative myasthenia gravis (SNMG) was held on February 9-11, 2024. The participants included experts in the field of adult and pediatric MG together with patient representatives. This workshop aimed to redefine SNMG in view of recent diagnostic and therapeutic updates and to identify patient unmet needs.

The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning.

Numerous cardioprotective interventions have been reported to reduce myocardial infarct size (IS) in pre-clinical studies. However, their translation for the benefit of patients with acute myocardial infarction (AMI) has been largely disappointing. One reason for the lack of translation is the lack of rigor and reproducibility in pre-clinical studies.

Aortic and Mitral Valve Endocarditis-Simply Left-Sided Endocarditis or Different Entities Requiring Individual Consideration?-Insights from the CAMPAIGN Database.

: Aortic valve infective endocarditis (AV-IE) and mitral valve infective endocarditis (MV-IE) are often grouped together as one entity: left-sided endocarditis. However, there are significant differences between the valves in terms of anatomy, physiology, pressure, and calcification tendency. This study aimed to compare AV-IE and MV-IE in terms of patient characteristics, pathogen profiles, postoperative outcomes, and predictors of mortality.

[Nursing and medical delegable measures for children and adolescents with cancer as outpatient outreach care - The pilot project KIK HomeCare].

Background: In the period from 2019 to 2022, pediatric hemato-oncological patients were cared for in a pilot project in North Rhine-Westphalia (NRW). The project delivered care at the homes of the patients as opposed to care at the clinics and included both general nursing as well as specific treatments that were delegated from physicians. Patients were admitted to this form of care upon referral by a physician.

Overview of the Use of Optical Coherence Tomography Angiography in Neovascular Age-Related Macular Degeneration.

The aim of this review is to present and discuss the use of optical coherence tomography angiography (OCTA) in age-related macular degeneration (AMD). OCTA is a non-invasive imaging procedure that gives a detailed indirect view of physiological and pathological vessels in the retina and choroid membrane. Compared with dye-based imaging, OCTA provides a segmented presentation of the individual vascular layers and plexuses, thus enabling previously unattainable differentiation and classification of pathological vascular changes within or underneath the retina.

Cardiac fibroblasts: answering the call.

Cardiac fibroblasts play a pivotal role in maintaining heart homeostasis by depositing extracellular matrix (ECM) to provide structural support for the myocardium, vasculature, and neuronal network and by contributing to essential physiological processes. In response to injury such as myocardial infarction or pressure overload, fibroblasts become activated, leading to increased ECM production that can ultimately drive left ventricular remodeling and progress to heart failure. Recently, the issued a call for papers on cardiac fibroblasts that yielded articles with topics spanning fibroblast physiology, technical considerations, signaling pathways, and interactions with other cell types.

Bardet-Biedl syndrome improved diagnosis criteria and management: Inter European Reference Networks consensus statement and recommendations.

Four European Reference Networks (ERN-EYE, ERKNet, Endo-ERN, ERN-ITHACA) have teamed up to establish a consensus statement and recommendations for Bardet-Biedl syndrome (BBS). BBS is an autosomal recessive ciliopathy with at least 26 genes identified to date. The clinical manifestations are pleiotropic, can be observed in utero and will progress with age.

Streamlined Intraoperative Brain Tumor Classification and Molecular Subtyping in Stereotactic Biopsies Using Stimulated Raman Histology and Deep Learning.

Purpose: Recent artificial intelligence algorithms aided intraoperative decision-making via stimulated Raman histology (SRH) during craniotomy. This study assesses deep learning algorithms for rapid intraoperative diagnosis from SRH images in small stereotactic-guided brain biopsies. It defines a minimum tissue sample size threshold to ensure diagnostic accuracy.

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.

Purpose: Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation.