Mineralocorticoid effects of fludrocortisone and hydrocortisone in primary adrenal insufficiency: EU-AIR patient data.

Purpose: Patients with primary adrenal insufficiency (PAI) require mineralocorticoid replacement therapy in addition to glucocorticoids. These therapies should be considered in combination because most glucocorticoids also possess mineralocorticoid activity. We aimed to investigate the relationship between fludrocortisone and hydrocortisone-equivalent dosing in patients with PAI.

Advancing preclinical biology for Ewing Sarcoma: an international effort.

Ewing sarcoma (EwS) is an aggressive bone and soft tissue cancer affecting adolescents and young adults. In vitro and in vivo models of EwS have been instrumental in advancing our understanding of EwS biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease where effective treatment options remain limited. Through an international collaborative effort between the Children's Oncology Group (COG) Bone Tumor Committee and the Euro Ewing Consortium (EEC), we review the current landscape of preclinical modeling used in EwS research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and non-mammalian xenografts) model systems.

Irritable Bowel Syndrome in Inflammatory Bowel Disease Patients: Prevalence, Etiology, and Treatment.

One in 4 patients with endoscopically confirmed quiescent inflammatory bowel disease (IBD) reports persistent gastrointestinal symptoms, which are often compatible with irritable bowel syndrome (IBS). The reporting of these IBS-type symptoms is associated with psychological comorbidity, impaired quality of life, and increased health care utilization. The brain-gut axis, which provides the link between the central nervous system and gastrointestinal tract, may facilitate these relationships.

Tumor transcriptome-wide expression classifiers predict treatment sensitivity in advanced prostate cancers.

Advanced prostate cancers respond to hormone therapy but outcomes vary and no predictive tests exist for informed treatment selection. To identify novel biomarker-treatment pairings, we examined associations between biological pathways and 14-year survival outcomes of patients randomized in practice-changing phase 3 trials (testing docetaxel or abiraterone). We included transcriptome-wide expression signatures and immunohistochemistry markers (Ki-67 and PTEN) on prostate tumors from 1,523 patients (832 metastatic).

International neuroblastoma risk group consortium: a model of a networking for rare cancers.

It is critical to share knowledge and harmonize approaches to optimize progress in rare cancers. The International Neuroblastoma Risk Group (INRG) Task Force was formed by the four major neuroblastoma cooperative groups in 2004 to achieve this goal. Strategies developed for neuroblastoma are an exemplar for other rare malignancies.

Point-of-Care Ionised Calcium Testing: Lab Validation and Clinical Feasibility Study.

Background: Patients undergoing thyroid and parathyroid surgery require frequent assessment of blood calcium levels to guide their management and currently such measurements are performed mostly in hospital environment on main laboratory platforms. The aim of this study was to explore the potential use of a non-medical LAQUA device designed to measure ionised calcium in environmental samples as a pocket-size point-of-care device able to measure blood calcium concentration in patients after thyroid and parathyroid surgery.

Methods: Protocol of the study consisted of 3 distinctive phases consisting of surveying the technological landscape and identifying currently available devices and technologies able to measure calcium in a small volume of whole blood easily, quickly and accurately (Phase 1), testing the potential candidate device in a laboratory (Phase 2) and performing a prospective, single arm study (IRAS ID 236079, Protocol number 18/0058, REC ref 19/LO/1740) during which simultaneous calcium measurements were performed on venous and capillary blood on LAQUA and "gold standard" platforms Roche Cobas-Calcium-Gen.

Mitochondrial bioenergetics and intracellular calcium concentration in primary myotubes from mouse models of malignant hyperthermia.

Background: Malignant hyperthermia (MH) is a potentially fatal hypermetabolic reaction to general anaesthesia arising from skeletal muscle calcium dysregulation. Previous studies of resting cells support an association between MH susceptibility, mitochondrial dysfunction, and defects in fatty acid metabolism, which are understood to be downstream consequences of calcium dysregulation. We hypothesised that in mouse models of MH susceptibility, genotypes associated with higher cytoplasmic calcium concentrations would have a proportionally higher mitochondrial oxygen consumption rate (OCR).

Pathology reporting of hepatoblastoma resections: recommendations from the international collaboration on cancer reporting.

Aims: Hepatoblastoma is the most common primary malignant tumour of the liver diagnosed in children and its incidence is increasing worldwide. Ongoing international clinical trials and scientific collaborative efforts are attempting to standardize the diagnosis, risk stratification and management of young patients diagnosed with this rare cancer, which includes surgical resection of the tumour. Here we report the international consensus-based dataset for the pathology reporting of hepatoblastoma resection specimens.

Glioblastoma in Adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) Consensus Review on Current Management and Future Directions.

Glioblastoma is the most common type of malignant primary brain tumor and a major cause of morbidity and mortality. In 2021 the World Health Organization updated the classification of Central Nervous System (CNS) tumors to restrict glioblastomas to isocitrate dehydrogenase-wildtype (IDHwt) tumors, improving understanding of the prognosis and optimal therapy for these tumors. This revision also enables more homogeneous populations of patients to be enrolled into clinical trials, facilitating the evaluation of novel therapies.

American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel.

Objective: Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality.

Methods: Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS.

Phase 3 Trials of Neoadjuvant, Perioperative, and Adjuvant Chemoimmunotherapy for Resectable, Early-Stage NSCLC: Comprehensive Review and Detailed Analysis.

Phase 3 trials of neoadjuvant, perioperative, and adjuvant immune checkpoint inhibitors combined with chemotherapy (ICI-CT) in resectable early-stage NSCLC (eNSCLC) have reported that all three approaches confer an event-free or disease-free survival benefit over CT alone, with acceptable safety profiles. All three strategies are approved standards of care for eNSCLC. This review provides a detailed analysis of these phase 3 ICI-CT trials and addresses the considerations regarding the selection of each approach, including protocol schema and baseline patient and tumor differences, preoperative staging, surgical outcomes, efficacy end points, safety, treatment disposition, and the programmed death-ligand 1 (PD-L1) efficacy biomarker.

Fifteen-minute consultation: Illness management in type 1 diabetes.

Children and young people with type 1 diabetes (T1D) often require support when faced with the common illnesses and infections of childhood. Illnesses particularly associated with fever can cause glucose management to be less predictable and more of a challenge, leading them to seek advice from healthcare professionals. In hours, this is often provided by specialist paediatric diabetes teams.

Excised DNA circles from V(D)J recombination promote relapsed leukaemia.

Extrachromosomal DNA amplification is associated with poor cancer prognoses. Large numbers of excised signal circles (ESCs) are produced as by-products of antigen receptor rearrangement during V(D)J recombination. However, current dogma states that ESCs are progressively lost through cell division.

Neurocognitive concerns and neurocognitive impairment in long-term survivors of oropharyngeal cancer post (chemo)radiotherapy.

Background: Little is known about neurocognitive concerns (NCC) and neurocognitive function (NCF) in survivors of oropharyngeal cancer (OPC) following (chemo)radiotherapy.

Methods: A multicentre cross-sectional study was conducted in non-surgically treated OPC. Using the Medical Outcomes Study Cognitive Functioning Scale (MOS-Cog), NCC were classed as having concerns at least some of the time (MOS-Cog score of ≤ 60 across all items).

Equity of participants in clinical trials in critical care and perioperative medicine research: a systematic review.

Background: Underrepresentation in critical care and perioperative randomised controlled trials (RCTs) limit generalisability and drive health inequity. This systematic review of large, high-quality RCTs analysed representation and reporting trends of equity data over 10 yr.

Methods: We searched MEDLINE, Embase, and Clinicaltrials.

Measurable/Minimal Residual Disease: What Method and What Cut-Off?

Minimal residual disease (MRD) testing has become a central response biomarker in clinical trials of time-limited treatment, with MRD-guided strategies under increasing evaluation. This article compares key technical and practical features of available MRD approaches and provides guidance on selecting the appropriate method and threshold for varied clinical applications.

Genetic Screening of a Nonsyndromic Amelogenesis Imperfecta Patient Cohort Using a Custom smMIP Reagent for Selective Enrichment of Target Loci.

Amelogenesis is the process of tooth enamel formation, and genetic variants disrupting it cause the Mendelian inherited disorder amelogenesis imperfecta (AI). AI patients have weak, discoloured or brittle enamel, caused by reduced enamel quantity or mineralisation. AI can occur in isolation or, less commonly, as part of a syndrome.

Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL.

With up to 10 years of follow-up, we report results from the final analysis of RESONATE-2 (NCT01722487/NCT01724346), a phase 3 study of first-line ibrutinib versus chlorambucil for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients aged ≥65 years with previously untreated CLL/SLL without del(17p) were randomly assigned to receive either single-agent ibrutinib (420 mg/day; n = 136) or chlorambucil (0.5-0.

Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan.

Introduction: Pegcetacoplan, the first C3 and C3b inhibitor for paroxysmal nocturnal hemoglobinuria (PNH), demonstrated efficacy and safety in C5 inhibitor-experienced and -naive patients in the phase 3 studies PEGASUS (NCT03500549) and PRINCE (NCT04085601), respectively. This integrated analysis of PEGASUS, PRINCE, and their subsequent open-label extension study (NCT03531255) evaluated pegcetacoplan long-term efficacy and safety.

Methods: Efficacy was assessed from pegcetacoplan initiation through 2.

Long-Range PCR and Nanopore Sequencing Enables High-Throughput Detection of TCF4 Trinucleotide Repeat Expansions in Fuchs Endothelial Corneal Dystrophy.

Introduction: Trinucleotide repeat expansion in CTG18.1, in intron 2 of TCF4 (MIM *602272, #613267), is the main cause of Fuchs endothelial corneal dystrophy (FECD), accounting for around 75% of cases in Caucasians. CTG18.

Health-related quality of life and unmet needs of people with epilepsy and their family caregivers: A systematic scoping review.

Introduction: People with epilepsy can experience limitations in their everyday lives due to their condition, impacting on health-related quality of life (HRQOL). We synthesized evidence on HRQOL and unmet needs in adult people with epilepsy and their family caregivers to provide a comprehensive overview of the impact of epilepsy and to identify opportunities for healthcare service improvements.

Methods: Systematic literature searches were conducted in CINAHL, Embase, Ovid MEDLINE, APA PsychInfo, Scopus, and grey literature databases (12 August 2024).

Safety, Efficacy, and Patient-Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, life-threatening disease associated with chronic intravascular hemolysis due to uncontrolled complement activation. PNH results in anemia with an increased risk of thrombosis, and often causes severe fatigue, and decreased physical function and health-related quality of life (QoL). We investigated the efficacy, safety, and patient-reported outcomes data of the combination of pozelimab (a fully human monoclonal antibody) and cemdisiran (an -acetylgalactosamine-conjugated small interfering ribonucleic acid) from a Phase 2 trial (NCT04811716) in patients with PNH who transitioned from pozelimab monotherapy.