Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

Effects of Retinol, Natural Pea Peptide and Antioxidant Blend in a Topical Formulation: In Vitro and Clinical Evidence.

Introduction: Retinol has a long history of treating skin conditions, including photoaging. However, skin irritation with repeated use of retinol is well documented. The present study assessed the effectiveness of a novel topical formulation, referred to as retinol topical formulation (RTF), to improve the quality of skin health.

Long-term Changes in Pain, Depression, Function and Informal Caregiving after Major Elective Surgeries Among Seriously Ill Older Adults.

Objective: To compare differences in pain, depression, function, and informal caregiving pre-and-post major elective surgery among older adults with and without serious illness; and determine if serious illness was independently associated with increasing pain, depression, assistance in activities of daily living (ADLs) and informal caregiving post-surgery.

Background: The American College of Surgeons has endorsed the integration of palliative care (PC) into surgical care in adults with serious illness but targets for PC during surgical episodes such as pain, depression, function, and informal caregiving are understudied.

Methods: We used Health and Retirement Study-linked Medicare data (2008-2018) to identify older (≥66 y) adults with and without serious illness who had major elective surgery.

Understanding Cognitive Aging Through White Matter: A Fixel-Based Analysis.

Diffusion-weighted imaging (DWI) has been frequently used to examine age-related deterioration of white matter microstructure and its relationship to cognitive decline. However, typical tensor-based analytical approaches are often difficult to interpret due to the challenge of decomposing and (mis)interpreting the impact of crossing fibers within a voxel. We hypothesized that a novel analytical approach capable of resolving fiber-specific changes within each voxel (i.

Emergence of Omicron FN.1 a descendent of BQ.1.1 in Botswana.

Botswana, like the rest of the world, has been significantly impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2022, we detected a monophyletic cluster of genomes comprising a sublineage of the Omicron variant of concern (VOC) designated as B.1.

FBG-driven simulation for virtual augmentation of fluoroscopic images during endovascular interventions.

Endovascular interventions are procedures designed to diagnose and treat vascular diseases, using catheters to navigate inside arteries and veins. Thanks to their minimal invasiveness, they offer many benefits, such as reduced pain and hospital stays, but also present many challenges for clinicians, as they require specialized training and heavy use of X-rays. This is particularly relevant when accessing (i.

Gaps in the management of adrenal insufficiency in melanoma survivors: a retrospective cohort study.

Background: Due to limited data on managing immunotherapy-induced secondary adrenal insufficiency (SAI) in melanoma survivors, this study investigated its management strategies and outcomes.

Methods: This retrospective cohort study analyzed melanoma patients treated with immune checkpoint inhibitors (ICIs) with SAI (Mel_SAI, n = 161), without SAI (Mel_CON, n = 168), and patients with pituitary adenoma-related SAI (Pit_SAI, n = 106) at our institution from January 2013 to November 2023. We compared glucocorticoid management patterns, quality of life using distress scores, and the impact of different glucocorticoid types on survival outcomes using Kaplan-Meier analysis.

Mixed Cardiogenic-Vasodilatory Shock: Current Insights and Future Directions.

This state-of-the-art review describes the potential etiologies, pathophysiology, and management of mixed shock in the context of a proposed novel classification system. Cardiogenic-vasodilatory shock occurs when cardiogenic shock is complicated by inappropriate vasodilation, impairing compensatory mechanisms, and contributing to worsening shock. Vasodilatory-cardiogenic shock occurs when vasodilatory shock is complicated by myocardial dysfunction, resulting in low cardiac output.

Association of social vulnerability and depression incidence post intracerebral haemorrhage: a cohort study.

Objectives: Survivors of intracerebral haemorrhage (ICH) are at high risk of incident depression, which is modified by social determinants of health (SDOH) and associated with worse functional outcomes. We sought to determine the role of prestroke SDOH in depression incidence after ICH to better characterise post-ICH outcomes.

Study Design: We analysed data from a cohort study of ICH survivors without prestroke depression, presenting at Massachusetts General Hospital between 2006 and 2017.

Deep learning-based classification of breast cancer molecular subtypes from H&E whole-slide images.

Classifying breast cancer molecular subtypes is crucial for tailoring treatment strategies. While immunohistochemistry (IHC) and gene expression profiling are standard methods for molecular subtyping, IHC can be subjective, and gene profiling is costly and not widely accessible in many regions. Previous approaches have highlighted the potential application of deep learning models on hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) for molecular subtyping, but these efforts vary in their methods, datasets, and reported performance.

Characterization of focused ultrasound blood-brain barrier disruption effect on inflammation as a function of treatment parameters.

The technology of focused ultrasound-mediated disruption of the blood-brain barrier (FUS-BBB opening) has now been used in over 20 Phase 1 clinical trials to validate the safety and feasibility of BBB opening for drug delivery in patients with brain tumors and neurodegenerative diseases. The primary treatment parameters, FUS intensity and microbubble dose, are chosen to balance sufficient BBB disruption to achieve drug delivery against potential acute vessel damage leading to microhemorrhage. However, other safety considerations due to second order effects caused by BBB disruption, such as inflammation and alteration of neurovascular function, are only beginning to be understood.

Days at Home After Transcatheter Mitral Valve Repair Versus Medical Therapy Alone in Heart Failure.

Background: Transcatheter edge-to-edge repair of the mitral valve (mTEER) reduced a hierarchical end point that included death and heart failure hospitalization in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation Trial). However, the magnitude to which mTEER increases the number of days a patient spends at home (DAH) in the first few years after treatment, a patient-centered end point not captured routinely in clinical trials, has not been evaluated. We compared 1- and 2-year DAH among patients with functional mitral regurgitation and heart failure randomized to mTEER plus medical therapy versus medical therapy alone (control) by linking the COAPT trial to comprehensive health care claims data.

Myocarditis in Patients Starting Combination Checkpoint Inhibitor Therapy: Analysis of a Commercial Claims Database.

Background: Immune checkpoint inhibitors have improved the clinical outcomes of several cancers but have also been associated with a greater risk of immune-related adverse effects, especially when combined. The objective of this study was to investigate the incidence of myocarditis in relation to the use of dual concurrent versus single immune checkpoint inhibitors therapies.

Methods And Results: A cohort study was conducted using medical and pharmacy claims data (2011-2022) from a large US commercial insurer.

Multiparametric Assessment of Right Ventricular Dysfunction in Heart Failure: An Analysis From PARAGON-HF.

Background: This study aims to characterize right ventricular dysfunction (RVD) in heart failure (HF) with preserved ejection fraction and understand the cumulative prognostic value of abnormal RV echocardiographic parameters in HF with preserved ejection fraction.

Methods And Results: Data from 809 patients in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction) echocardiographic substudy (55% women, mean age 74±8 years) were analyzed. Correlates of RVD (defined as tricuspid annular plane systolic excursion <1.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction and With Reduced Ejection Fraction According to the Prognostic Nutritional Index: Findings From PARADIGM-HF and PARAGON-HF.

Background: The importance of nutritional status is underappreciated in patients with heart failure (HF). This study aimed to describe the range of the prognostic nutrition index (PNI), and the clinical characteristics and outcomes according to PNI, in patients with HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The primary outcome was the composite of HF hospitalization or cardiovascular death.

Real-world treatment patterns, healthcare resource utilisation and costs in patients with SLE in the USA.

Objective: To evaluate the treatment patterns, medication adherence, concomitant corticosteroid use, factors influencing sequence of therapies (SOTs), healthcare resource utilisation (HCRU) and associated costs in adults with SLE in the USA.

Methods: Claims data from the Merative MarketScan Commercial and Medicare Supplemental Database between 2011 and 2019 were used to identify patients with incident SLE. The date of first claim with SLE was defined as the index date, with a 24-month pre-index and ≥24-month post-index period.

Anatomy-centred deep learning improves generalisability and progression prediction in radiographic sacroiliitis detection.

Purpose: To examine whether incorporating anatomy-centred deep learning can improve generalisability and enable prediction of disease progression.

Methods: This retrospective multicentre study included conventional pelvic radiographs of four different patient cohorts focusing on axial spondyloarthritis collected at university and community hospitals. The first cohort, which consisted of 1483 radiographs, was split into training (n=1261) and validation (n=222) sets.

A one-day acceptance and commitment therapy workshop for the prevention of chronic post-surgical pain and long-term opioid use following spine surgery: Protocol for a pilot feasibility randomized controlled trial.

Background: Back pain is increasingly common, leading to more spine surgeries. While most people experience pain relief and improved function after surgery, many continue to suffer from chronic post-surgical pain (CPSP) with limited functional improvement. CPSP is often treated with opioids, raising concerns about misuse, poor functional outcomes, and broader public health impacts.

A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant, trehalose monomycolate.

Mycobacterium tuberculosis causes human tuberculosis. As mycobacteria are protected by thick lipid cell wall, humans have developed immune responses against diverse mycobacterial lipids. Most of these immunostimulatory lipids are known as adjuvants acting through innate immune receptors, such as C-type lectin receptors.

Ubiquitin-mediated recruitment of the ATG9A-ATG2 lipid transfer complex drives clearance of phosphorylated p62 aggregates.

Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress.

Activated kynurenine pathway metabolism by YKL-40 establishes an inhibitory immune microenvironment and drives glioblastoma development.

Background: Glioblastoma (GB) is the stage IV of glioma and mesenchymal GB represents the most common and malignant subtype characterized with elevated expression of a mesenchymal marker YKL-40 and resistance to immune drug therapy. Here, we determined if YKL-40 regulates kynurenine (Kyn) pathway (KP) metabolism that contributes to establishing an immune suppressive microenvironment in GB.

Methods: Tumor cells expressing YKL-40 from GB patients were isolated and activated cellular metabolisms were identified via gene microarray analysis.

Significant Environmental Factors in the Drift of Electrical Properties in Conductive Nano-Composite Sensors for Biomechanical Motion-Tracking.

Wearable nanocomposite stretch sensors are an exciting new development in biomaterials for biomechanical motion-tracking technology, with applications in the treatment of low back pain, knee rehabilitation, fetal movement tracking, and other fields. When strained, the resistance of the low-cost sensors is reduced, enabling human motion to be monitored using a suitable sensor array. However, current sensor technologies have exhibited significant drift, in the form of increased electrical resistance, if left stored in typical room conditions.

Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab.

Background: Concerns persist regarding the cognitive safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. Although short-term studies are reassuring, the long-term cognitive effects of sustained exposure to very low LDL cholesterol levels through combined proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition and statin therapy remain unknown.

Methods: This prospective study enrolled a subset of adults with atherosclerotic cardiovascular disease who had completed a neurocognitive substudy (EBBINGHAUS) of a placebo-controlled randomized trial of evolocumab (FOURIER) and were eligible for a long-term open-label extension.