A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

How well do plasma Alzheimer's disease biomarkers reflect the CSF amyloid status?

Background: Can plasma biomarkers as well as cerebrospinal fluid (CSF) perform in the separation of amyloid-beta-positive (Aβ+) vs amyloid-beta-negative (Aβ-) groups across an age range seen in an NHS cognitive disorder clinic?

Methods: As part of the routine diagnostic investigation of 111 clinic patients who had contemporaneous blood and CSF samples taken, patients were categorised into Aβ+ and Aβ- groups based on their CSF in an Aβ42/40 ratio. We then evaluated four single molecule array (Simoa) Quanterix assays, quantifying single plasma analytes and ratios (p-tau217, p-tau217/Aβ42 ratio, p-tau181, p-tau181/Aβ42 ratio and Aβ42/40 ratio) in their ability to distinguish between these groups and the effect of age.

Results: The median (range) age of participants was 66 (55-79) years with 48 females (43.

Histotripsy of the Proximal Ureter and Renal Pelvis: Evaluation of Urothelial Injury in a Porcine Survival Model.

Purpose: To evaluate the response of the ureter and renal pelvis to direct targeting by histotripsy guided by cone-beam computed tomography (CT) in a human-scale porcine chronic-survival model.

Materials And Methods: Bilateral ureteral histotripsy treatments were completed on 6 female swine (n = 12). Animals were divided into 2 groups: (a) acute (n = 2 animals, 4 treatments, sacrificed at Day 0) and (b) chronic (n = 4 animals, 8 treatments, sacrificed at Day 7 [n = 2] and Day 28 [n = 2]).

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

Pain Outcomes Among Medical Centers With High vs Low Specialist Palliative Care Reach Among People With Heart Failure.

Pain affects more than 60% of people with heart failure (HF), with increasing frequency and severity towards the end of life (EOL). We examined if family-rated pain near EOL was associated with rates of specialist palliative care (SPC) among patients with HF. We conducted a retrospective cohort study among 1095 decedents with advanced HF (aHF = ≥2 hospitalizations) from 83 Veterans Affairs Medical Centers (VAMCs) between 2018-2020.

Paraneoplastic Resolution Holds Prognostic Utility in Patients with Metastatic Renal Cell Carcinoma.

The presence of paraneoplastic syndromes (PNS) in patients with renal cell carcinoma (RCC) is associated with worse survival; however, little is known about whether resolution of PNS after intervention has any prognostic value. We sought to determine if resolution of PNS by one year after cytoreductive nephrectomy was significantly associated with improved overall survival (OS) and cancer-specific survival (CSS). We retrospectively reviewed a prospectively maintained nephrectomy database for patients with any histology metastatic RCC (mRCC) who underwent nephrectomy between 2000 and 2022.

Use of Hospice and End-of-Life Care Quality Among Medical Centers with High Versus Lower Specialist Palliative Care Reach Among People with Heart Failure: An Observational Study.

Rates of specialist palliative care (SPC) vary among Veterans Affairs Medical Centers (VAMCs) for people with advanced heart failure (aHF). We evaluated the associations between facility rates of SPC reach and the quality of end of life (EOL) care received among this population. We conducted a retrospective cohort study among 3681 people with aHF who died in 83 VAMCs from 2018 to 2020.

Ten Years of Bipolar Telehealth: Program Evaluation of a Team-Based Telemental Health Clinic.

Telemental health via videoconferencing (TMH-V) can overcome many of the barriers to accessing quality mental health care. Toward this end, in 2011, the U.S.

Lysosomal LRRC8 complex regulates lysosomal pH, morphology and systemic glucose metabolism.

The lysosome integrates anabolic signalling and nutrient-sensing to regulate intracellular growth pathways. The leucine-rich repeat containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signalling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes.

ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic.

Introduction: Reducing Optic Atrophy 1 (OPA1) expression in skeletal muscle in male mice induces Activation Transcription Factor 4 (ATF4) and the integrated stress response (ISR). Additionally, skeletal muscle secretion of Fibroblast Growth Factor 21 (FGF21) is increased, which mediates metabolic adaptations including resistance to diet-induced obesity (DIO) and glucose intolerance in these mice. Although FGF21 induction in this model can be reversed with pharmacological attenuation of ER stress, it remains to be determined if ATF4 is responsible for FGF21 induction and its metabolic benefits in this model.

Comparative analysis of two independent Myh6-Cre transgenic mouse lines.

We have previously shown that the promoter drives Cre expression in a subset of male germ line cells in three independent mouse lines, including two transgenic lines and one knock-in allele. In this study, we further compared the tissue-specificity of the two transgenic mouse lines, through examining the expression of tdTomato (tdTom) red fluorescence protein in multiple internal organs, including the heart, brain, liver, lung, pancreas and brown adipose tissue. Our results show that mainly activates tdTom reporter in the heart, whereas activates tdTom expression significantly in the heart, and in the cells of liver, pancreas and brain.

BATokines in metabolic liver disease: good cops or bad cops?

The systemic regulation of metabolic dysfunction-associated liver disease remains poorly understood. In this issue, Hsiao et al (2024) identify PCPE-1 as a brown-adipose tissue-derived mediator of hepatic fibrosis, integrating context-dependent ER stress-signaling.

Endothelial metabolic control of insulin sensitivity through resident macrophages.

Endothelial cells (ECs) not only form passive blood conduits but actively contribute to nutrient transport and organ homeostasis. The role of ECs in glucose homeostasis is, however, poorly understood. Here, we show that, in skeletal muscle, endothelial glucose transporter 1 (Glut1/Slc2a1) controls glucose uptake via vascular metabolic control of muscle-resident macrophages without affecting transendothelial glucose transport.

IRS2 Signaling Protects Against Stress-Induced Arrhythmia by Maintaining Ca Homeostasis.

Background: The docking protein IRS2 (insulin receptor substrate protein-2) is an important mediator of insulin signaling and may also regulate other signaling pathways. Murine hearts with cardiomyocyte-restricted deletion of (cIRS2-KO) are more susceptible to pressure overload-induced cardiac dysfunction, implying a critical protective role of IRS2 in cardiac adaptation to stress through mechanisms that are not fully understood. There is limited evidence regarding the function of IRS2 beyond metabolic homeostasis regulation, particularly in the context of cardiac disease.

Oligodendroglial fatty acid metabolism as a central nervous system energy reserve.

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts.

Advice for dementia carers: A critique of the literature.

Although hundreds of advice manuals for dementia carers have been published, most have serious limitations. They emphasize the various problems family members experience without noting the social and political context within which caring unfolds. As a result, they eschew structural reforms in favor of individual solutions, including self-care.

Myocardial infarction causes sex-dependent dysfunction in vagal sensory glutamatergic neurotransmission that is mitigated by 17β-estradiol.

Parasympathetic dysfunction after chronic myocardial infarction (MI) is known to predispose ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]). VT/VF after MI is more common in males than females. The mechanisms underlying the decreased vagal tone and the associated sex difference in the occurrence of VT/VF after MI remain elusive.

Leveraging Electronic Health Records to Assess Residential Mobility Among Veterans in the Veterans Health Administration.

Background: Residential mobility, or a change in residence, can influence health care utilization and outcomes. Health systems can leverage their patients' residential addresses stored in their electronic health records (EHRs) to better understand the relationships among patients' residences, mobility, and health. The Veteran Health Administration (VHA), with a unique nationwide network of health care systems and integrated EHR, holds greater potential for examining these relationships.