Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

Introduction: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline.

Methods: We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort.

Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: A Randomized Controlled Phase 3 Study.

Background: We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension.

Methods: In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death.

Efficacy and safety of pulsed field ablation compared to cryoballoon ablation in the treatment of atrial fibrillation: a meta-analysis.

Aims: Pulmonary vein isolation (PVI) represents the gold standard in the treatment of atrial fibrillation (AF) and the use of single-shot techniques, such as cryoballoon ablation (CBA) and pulsed field ablation (PFA) using a pentaspline catheter, has gained prominence. Recent studies hypothesize that PFA might be superior to CBA, although procedural efficacy and safety data are inconsistent. A meta-analysis was conducted to compare both energy sources for the treatment of AF.

Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings.

BCG Vaccination-Associated Lower HbA1c and Increased CD25 Expression on CD8 T Cells in Patients with Type 1 Diabetes in Ghana.

BCG vaccination affects other diseases beyond tuberculosis by unknown-potentially immunomodulatory-mechanisms. Recent studies have shown that BCG vaccination administered during overt type 1 diabetes (T1D) improved glycemic control and affected immune and metabolic parameters. Here, we comprehensively characterized Ghanaian T1D patients with or without routine neonatal BCG vaccination to identify vaccine-associated alterations.

Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates.

(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug Administration (FDA) approval of transcatheter device closure; (2) Methods: We performed a 10-year (2014-2023) single-institution retrospective study of premature infants (<37 weeks) and compared clinical characteristics and neonatal morbidities between neonates that underwent surgical ligation before (epoch 1) and after (epoch 2) FDA approval of transcatheter closure; (3) Results: We identified 120 premature infants that underwent surgical ligation ( = 94 before, = 26 after FDA approval). Unfavorable PDA morphology, active infection, and recent abdominal pathology were the most common reasons for surgical ligation over device occlusion in epoch 2. There were no differences in demographics, age at closure, or outcomes between infants who received surgical ligation in the two epochs; (4) Conclusions: Despite increasing trends for transcatheter PDA closure in premature infants, surgical ligation persists due to unfavorable ductal morphology, active infection, or abdominal pathology.

Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure.

Objective: Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults.

Retinal small vessel pathology is associated with disease burden in multiple sclerosis.

Background: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA).

Objectives: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology.

Methods: In this cross-sectional study, including 259 relapsing-remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools.

Real world propensity score matched analysis evaluating the influence of en-bloc vs. non en-bloc techniques, energy and instrumentation on enucleation outcomes for large and very large prostates.

Purpose: The primary aim of the study was to evaluate if en-bloc vs. non en-bloc made a difference to intra-, peri- and post-operative surgical outcomes of anatomical endoscopic enucleation (AEEP) in large (> 80 cc) and very large prostates (> 200 cc). The secondary aim was to determine the influence of energy and instruments used.

Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study).

Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit"; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated.

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

Background And Objectives: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium).

The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs.

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study.

Background: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients.

Methods: We conducted an international retrospective study of MeVO cases.

Risk of Cardiac Implantable Electronic Device Infection after Early versus Delayed Lead Repositioning.

(1) Background: Early reintervention increases the risk of infection of cardiac implantable electronic devices (CIEDs). Some operators therefore delay lead repositioning in the case of dislocation by weeks; however, there is no evidence to support this practice. The aim of our study was to evaluate the impact of the timing of reoperation on infection risk.

Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model.

Background And Objective: Vosoritide is a recently approved therapy for achondroplasia, the most common form of disproportionate short stature, that has been shown to be well tolerated and effective in increasing linear growth. This study aimed to develop a population pharmacokinetic (PPK) model to characterize pharmacokinetics (PK) of vosoritide and establish a weight-band dosing regimen.

Methods: A PPK model was developed using data from five clinical trials in children with achondroplasia (aged 0.

Toward a Universal Definition of Etiologies in Heart Failure: Categorizing Causes and Advancing Registry Science.

Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.

Metastatic Breast Cancer: Prolonging Life in Routine Oncology Care.

Overall survival (OS) of patients with metastatic breast cancer (MBC) has improved within controlled clinical trials. Whether these advances translate into improved OS in routine care is controversial. We therefore analyzed retrospectively unselected female patients from five oncology group practices and one university outpatient clinic, whose initial diagnosis of MBC was between 1995 and 2022.

Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.

The aetiology of heart failure with preserved ejection fraction (HFpEF) is heterogenous and overlaps with that of several comorbidities like atrial fibrillation, diabetes mellitus, chronic kidney disease, valvular heart disease, iron deficiency, or sarcopenia. The diagnosis of HFpEF involves evaluating cardiac dysfunction through imaging techniques and assessing increased left ventricular filling pressure, which can be measured directly or estimated through various proxies including natriuretic peptides. To better narrow down the differential diagnosis of HFpEF, European and American heart failure guidelines advocate the use of different algorithms including comorbidities that require diagnosis and rigorous treatment during the evaluation process.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA).

Methods And Results: Eighty-three international experts met in Münster for 2 days in September 2023.

A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels.

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically.

[Minimally-Invasive Surgical Techniques (MIST): Shedding Light on the Mist].

As life expectancy increases and there is growing demand for BPH treatments, innovative technologies have been developed, allowing for swift recovery, symptom relief, low complication rates, and the possibility of performing procedures on an outpatient basis, often under local anaesthesia. This review aims to describe the outcomes of newly developed minimally-invasive surgical therapies (MIST) for BPH treatment in terms of functional voiding parameters and sexual function. These therapies are categorized into primarily ablative (Aquablation [Aquabeam]), non-ablative (Prostatic Urethral Lift (PUL, Urolift), temporary implantable devices [iTind]), and secondarily ablative procedures (convective water vapor ablation, Rezum, Prostate Artery Embolization [PAE]).

Safety and Efficacy of Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Previously Untreated Patients with Hemophilia B.

 Recombinant fusion protein linking coagulation factor IX (FIX) with albumin (rIX-FP) has been shown to be an effective, well-tolerated treatment for patients with severe hemophilia B who had previously received factor replacement therapy. This study investigated the safety and efficacy of rIX-FP in previously untreated patients (PUPs).  Patients with moderately severe/severe hemophilia B (≤2% FIX) previously untreated with FIX replacement products received rIX-FP (25-75 IU/kg) prophylaxis weekly or on-demand treatment over ≥50 exposure days (EDs).