Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Comparison of Outcomes of Deep Sclerectomy, Canaloplasty, and Viscocanaloplasty: A Multi-Centred Study.

Prcis: Deep sclerectomy (DS) and canaloplasty provide better intraocular pressure (IOP) control than viscocanalostomy. DS required less glaucoma medications but more interventions to reach target IOP.

Purpose: To compare real-world outcomes of three non-penetrating glaucoma surgery (NPGS) techniques.

Clinical and imaging spectrum of non-congenital dominant ACTN2 myopathy.

Background: Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy.

Methods: Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium.

Balance recovery and its link to vestibular agnosia in traumatic brain injury: a longitudinal behavioural and neuro-imaging study.

Background: Vestibular dysfunction causing imbalance affects c. 80% of acute hospitalized traumatic brain injury (TBI) cases. Poor balance recovery is linked to worse return-to-work rates and reduced longevity.

Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

CoGames: Development of an adaptive smartphone-based and gamified monitoring tool for cognitive function in Multiple Sclerosis.

Aim: As part of the development of a smartphone-based app for monitoring MS disease activity and progression (dreaMS, NCT05009160), we developed six gamified tests with multiple difficulty levels as a monitoring tool for cognition. This study quantified the relative difficulty between levels and investigated their reliability, ability to depict practice effects, and user acceptance.

Methods: Healthy volunteers played each game, covering five cognitive domains, twice per day for 11 consecutive days.

Utilizing deep learning to predict Alzheimer's disease and mild cognitive impairment with optical coherence tomography.

Introduction: Diagnostic performance of optical coherence tomography (OCT) to detect Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains limited. We aimed to develop a deep-learning algorithm using OCT to detect AD and MCI.

Methods: We performed a cross-sectional study involving 228 Asian participants (173 cases/55 controls) for model development and testing on 68 Asian (52 cases/16 controls) and 85 White (39 cases/46 controls) participants.

Advanced tissue technologies of blood-brain barrier organoids as high throughput toxicity readouts in drug development.

Recent advancements in engineering Complex models (CIVMs) such as Blood-brain barrier (BBB) organoids offer promising platforms for preclinical drug testing. However, their application in drug development, and especially for the regulatory purposes of toxicity assessment, requires robust and reproducible techniques. Here, we developed an adapted set of orthogonal image-based tissue methods including hematoxylin and eosin staining (HE), immunohistochemistry (IHC), multiplex immunofluorescence (mIF), and Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to validate CIVMs for drug toxicity assessments.

Extending health equity to people with moderate and mild hemophilia A: revisiting the HAVEN 6 trial.

Congenital hemophilia A (HA) disease severity has traditionally been categorized according to intrinsic factor (F)VIII levels, with <1% of normal indicating severe HA, 1% to 5% moderate HA, and 6% to 40% mild HA. However, mounting evidence illustrates considerable variability in bleeding phenotype regardless of FVIII level. Despite treatment advances, people with moderate or mild HA may be neglected, as treatment guidelines and established norms focus on FVIII levels, and many clinical trials do not include people with FVIII > 1%.

Study Design and Baseline Characteristics of ALIGN, a Randomized Controlled Study of Atrasentan in Patients With IgA Nephropathy.

Introduction: Endothelin A (ETA) receptor activation is a driver of proteinuria, kidney inflammation, and fibrosis in IgA nephropathy (IgAN). Atrasentan, a selective ETA receptor antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. ALIGN (NCT04573478) is a phase 3, randomized, double-blind, placebo-controlled clinical trial of atrasentan in patients with IgAN at high risk of kidney function loss.

Outcome of Patients Transplanted for C3 Glomerulopathy and Primary Immune Complex-Mediated Membranoproliferative Glomerulonephritis.

Introduction: Approximately 50% of patients with C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) reach kidney failure 10 years after diagnosis. Because these patients are generally young, the majority will be listed for kidney transplantation (KTx). However, reported outcomes in patients transplanted for C3G and IC-MPGN are heterogeneous and conflicting, because they are mainly based on retrospective monocentric studies.

Excess cardiometabolic risk in children and adolescents initiating antipsychotic treatment compared to young adults: results from a nationwide cohort study.

Antipsychotic treatment is associated with cardiometabolic risks that may be especially detrimental to children and adolescents. In this Danish population-based cohort study, we included individuals with psychiatric diagnoses who initiated antipsychotics in 2000-2021 at age 6-31 years. We assessed the risk of cardiometabolic adverse events up to 10 years following incident exposure to antipsychotics, compared to age- and sex-matched unexposed individuals with psychiatric diagnoses.

Social issues in general practice - a survey assessing the interprofessional perspective of general practitioners and social workers regarding frequency, challenges, and needs.

Background: Health or illness and social issues cannot be viewed in isolation. Social problems can influence well-being and disease. General Practitioners (GPs) are requested to offer counselling opportunities to respond to the social issues of their patients adequately.

Safety and efficacy of the ROCK-2-inhibitor Belumosudil in cGvHD treatment - a retrospective, German-Swiss multicenter real-world data analysis.

Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD). In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers. A total of 33 adult patients (median age 59 years) with moderate (n = 2) or severe (n = 31) cGvHD were treated on individual request due to lack of EMA approval.

Understanding the spread of agriculture in the Western Mediterranean (6th-3rd millennia BC) with Machine Learning tools.

The first Neolithic farmers arrived in the Western Mediterranean area from the East. They established settlements in coastal areas and over time migrated to new environments, adapting to changing ecological and climatic conditions. While farming practices and settlements in the Western Mediterranean differ greatly from those known in the Eastern Mediterranean and central Europe, the extent to which these differences are connected to the local environment and climate is unclear.

Reduced Lower Body Muscular Strength and Endurance among Adult Survivors of Childhood Cancer.

Introduction: Impaired physical fitness is a possible late effect among adult survivors of childhood cancer (ASCC). Our study describes lower body muscular strength and endurance among ASCC using the 1-minute sit-to-stand (1-min STS) test, compares them with the general population, identifies risk factors, and describes changes over time.Methods: In a prospective multicenter cohort study, we invited ASCC ≥18 years of age at study, diagnosed between ages 0-20 treated in five pediatric oncology centers across Switzerland from 1976-2017 who survived ≥5 years for a 1-min STS test.

Individual Assembly of Radical Molecules on Superconductors: Demonstrating Quantum Spin Behavior and Bistable Charge Rearrangement.

High-precision molecular manipulation techniques are used to control the distance between radical molecules on superconductors. Our results show that the molecules can host single electrons with a spin 1/2. By changing the distance between tip and sample, a quantum phase transition from the singlet to doublet ground state can be induced.

An assessment of burden associated with problem joints in children and adults with moderate or severe haemophilia A: analysis of the CHESS-Paediatrics and CHESS II cross-sectional studies.

Background: Clinical research has offered many definitions and fragmented perspectives of joint morbidity in haemophilia. As joint damage, pain and mobility impairment can be present without clinical record of persistent bleeding, a person-centric joint morbidity characterisation remained a priority for the haemophilia community, giving rise to the 'problem joint' concept. As diagnosing and managing joint morbidity is critical, the aim of this study was to analyse the holistic burden of problem joints in people with moderate or severe haemophilia A (HA).

Therapeutic development to accelerate malaria control through intentional intervention layering.

The clinical development of novel vaccines, injectable therapeutics, and oral chemoprevention drugs has the potential to deliver significant advancements in the prevention of Plasmodium falciparum malaria. These innovations could support regions in accelerating malaria control, transforming existing intervention packages by supplementing interventions with imperfect effectiveness or offering an entirely new tool. However, to layer new medical tools as part of an existing programme, malaria researchers must come to an agreement on the gaps that currently limit the effectiveness of medical interventions for moderate to low transmission settings.

Heart Rate Variability Does Not Predict Recurrence of Apnoea of Prematurity After Ceasing Caffeine Therapy: A Prospective Cohort Study.

Aim: We evaluated whether sample entropy of heart rate time series could serve as a biomarker for guiding caffeine cessation in preterm infants treated for apnoea of prematurity (AOP). We also assessed associations of sample entropy with weeks of gestation, clinical morbidity, AOP frequency and caffeine reinitiation.

Methods: We conducted a prospective single-centre study at the University Children's Hospital Basel, Switzerland, from July 2019 to June 2020.

Benchmarking R&D success rates of leading pharmaceutical companies: an empirical analysis of FDA approvals (2006-2022).

Previous analyses provide an industry benchmark of ∼10% for the success rate in clinical development. However, prior analyses were limited by a narrow timeframe, a diverse research focus, biases in phase-to-phase transition methodology or a focus on specific use cases. We calculated unbiased input:output ratios (Phase I to FDA new drug approval) to analyze the likelihood of first approval using data from clinicaltrials.

Insights into eye genetics and recent advances in ocular gene therapy.

The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age.

Outcome of a Mix-and-Match Approach with a Monofocal Aspherical and a Bifocal Extended Depth-of-Focus Intraocular Lens to Achieve Extended Monovision in Cataract Patients.

Background: Extended monovision is a novel mix-and-match approach that has been recently introduced. It involves implanting an aspherical monofocal intraocular lens (IOL) for distance vision in the dominant eye, and a bifocal extended depth-of-focus (EDOF) IOL in the nondominant eye. The target refraction for the nondominant eye is - 1.