Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.

Objective: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC.

Methods: The INMARC database was queried for T1aN0M0 RCC.

Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry.

Background: To evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP).

Patients And Methods: We queried the International Marker Consortium for Renal Cancer database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (cc) RCC, chromophobe (ch) RCC, papillary (p) RCC, and variant histology (vh) RCC; and according to CRP (mg/L): low CRP ≤5 and high CRP >5.

United States-Mexico Border Disparities in Alcoholic Liver Disease Mortality: A Cross-Sectional Analysis 1999-2020.

Background: US-Mexico (US-MX) border regions are impacted by socioeconomic disadvantages. Alcohol use disorder remains widely prevalent in US-MX border regions, which may increase the risk of alcoholic liver disease (ALD).

Goals: We aimed to characterize ALD mortality trends in border regions compared to non-border regions from 1999 to 2020 in the United States (US).

Unraveling the BMI paradox in different renal cortical tumors: insights from the INMARC registry.

Objective: To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC).

Methods: We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m, Asian BMI >27.

Partial versus radical nephrectomy for complex renal mass: multicenter comparative analysis of functional outcomes (Rosula collaborative group).

Background: Utility of partial nephrectomy (PN) for complex renal mass (CRM) is controversial. We determined the impact of surgical modality on postoperative renal functional outcomes for CRM.

Methods: We retrospectively analyzed a multicenter registry (ROSULA).

Proposal for a Two-Tier Re-classification of Stage IV/M1 domain of Renal Cell Carcinoma into M1 ("Oligometastatic") and M2 ("Polymetastatic") subdomains: Analysis of the Registry for Metastatic Renal Cell Carcinoma (REMARCC).

Purpose: We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC).

Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, "Oligometastatic") and M2 (>3, "Polymetastatic").

Recent Advances in the Management of Localized and Locally Advanced Renal Cell Carcinoma: A Narrative Review.

Purpose: To review the current status of surgical and procedural treatments for renal cell carcinoma (RCC), focusing on oncological and functional outcomes, and the use of techniques for advanced disease over the last 10 years.

Findings: Partial nephrectomy (PN) has become the reference standard for most T1 and T2 masses. In cT2 RCC, PN exhibits oncological equivalence and improved functional outcomes compared to radical nephrectomy (RN).

Partial or radical nephrectomy for complex renal mass: a comparative analysis of oncological outcomes and complications from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

Purpose: To compare outcomes of robotic-assisted partial nephrectomy (RAPN) and minimally invasive radical nephrectomy (MIS-RN) for complex renal masses (CRM).

Methods: We conducted a retrospective multicenter analysis of CRM patients who underwent MIS-RN and RAPN. CRM was defined as RENAL score 10-12.

Age-Related Differences in Oncological Outcomes in Renal Cell Carcinoma: Impact of Functional Conservation as Measured by Postoperative eGFR.

Introduction: We sought to determine whether loss of renal function increases risk of recurrence and metastases in renal cell carcinoma (RCC), and whether this impact was age-related.

Materials And Methods: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry. Patients were separated into younger (<65 years old) and elder (≥65 years old) age groups, and rates of de novo estimated glomerular filtration rate (eGFR<45 mL/min/1.

Association of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and De Ritis ratio with mortality in renal cell carcinoma: A multicenter analysis.

Background: Several markers of inflammation have been associated with oncologic outcomes. Prognostic markers are not well-defined for renal cell carcinoma (RCC). We sought to investigate the association of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and De Ritis ratio with mortality in RCC.

Young age is associated with decreased recurrence for renal cell carcinoma.

Introduction: We aimed to examine stage-specific oncologic outcomes for young versus conventional-age patients with localized disease in a modern cohort.

Materials And Methods: The Surveillance, Epidemiology and End Results database was queried for patients with T1-T2N0M0 kidney cancer from 1975-2016, including clear cell, papillary, and chromophobe renal cell carcinoma. Patients were stratified into ≤ 40 years-old or > 40 years-old cohorts and underwent definitive treatment via percutaneous ablation, partial nephrectomy, or radical nephrectomy.

The RNA-binding protein Quaking regulates multiciliated and basal cell abundance in the developing lung.

RNA-binding proteins (RBPs) form complexes with RNA, changing how the RNA is processed and thereby regulating gene expression. RBPs are important sources of gene regulation during organogenesis, including the development of lungs. The RBP called Quaking (QK) is critical for embryogenesis, yet it has not been studied in the developing lung.

PAN-AMPK Activation Improves Renal Function in a Rat Model of Progressive Diabetic Nephropathy.

Metabolic dysregulation and mitochondrial dysfunction are important features of acute and chronic tissue injury across species, and human genetics and preclinical data suggest that the master metabolic regulator 5'-adenosine monophosphate-activated protein kinase (AMPK) may be an effective therapeutic target for chronic kidney disease (CKD). We have recently disclosed a pan-AMPK activator, MK-8722, that was shown to have beneficial effects in preclinical models. In this study we investigated the effects of MK-8722 in a progressive rat model of diabetic nephropathy to determine whether activation of AMPK would be of therapeutic benefit.

Engineering Glucose Responsiveness Into Insulin.

Insulin has a narrow therapeutic index, reflected in a small margin between a dose that achieves good glycemic control and one that causes hypoglycemia. Once injected, the clearance of exogenous insulin is invariant regardless of blood glucose, aggravating the potential to cause hypoglycemia. We sought to create a "smart" insulin, one that can alter insulin clearance and hence insulin action in response to blood glucose, mitigating risk for hypoglycemia.

HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.

Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented by two protective (B*57 and B*27) and one non-protective (A*02) MHC-I types. Libraries of HIV-1 with saturation mutagenesis of CTL epitopes are propagated with and without CTL selective pressure to define the fitness landscapes for epitope mutation and escape from CTLs via deep sequencing.

Phenotyping of adipose, liver, and skeletal muscle insulin resistance and response to pioglitazone in spontaneously obese rhesus monkeys.

Insulin resistance and diabetes can develop spontaneously with obesity and aging in rhesus monkeys, highly similar to the natural history of obesity, insulin resistance, and progression to type 2 diabetes in humans. The current studies in obese rhesus were undertaken to assess hepatic and adipose contributions to systemic insulin resistance-currently, a gap in our knowledge-and to benchmark the responses to pioglitazone (PIO). A two-step hyperinsulinemic-euglycemic clamp, with tracer-based glucose flux estimates, was used to measure insulin resistance, and in an intervention study was repeated following 6 wk of PIO treatment (3 mg/kg).

Gene expression in WAT from healthy humans and monkeys correlates with FGF21-induced browning of WAT in mice.

Objective: Identify a gene expression signature in white adipose tissue (WAT) that reports on WAT browning and is associated with a healthy phenotype.

Methods: RNA from several different adipose depots across three species were analyzed by whole transcriptome profiling, including 1) mouse subcutaneous white fat, brown fat, and white fat after in vivo treatment with FGF21; 2) human subcutaneous and omental fat from insulin-sensitive and insulin-resistant patients; and 3) rhesus monkey subcutaneous fat from healthy and dysmetabolic individuals.

Results: A "browning" signature in mice was identified by cross-referencing the FGF21-induced signature in WAT with the brown adipose tissue (BAT) vs.

Downstream signaling pathways in mouse adipose tissues following acute in vivo administration of fibroblast growth factor 21.

FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers.

Positron emission mammography (PEM): effect of activity concentration, object size, and object contrast on phantom lesion detection.

Purpose: To characterize the relationship between lesion detection sensitivity and injected activity as a function of lesion size and contrast on the PEM (positron emission mammography) Flex Solo II scanner using phantom experiments.

Methods: Phantom lesions (spheres 4, 8, 12, 16, and 20 mm diameter) were randomly located in uniform background. Sphere activity concentrations were 3 to 21 times the background activity concentration (BGc).

Heat induces gene amplification in cancer cells.

Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms.

Background parenchymal enhancement on breast MRI: impact on diagnostic performance.

Objective: Breast density is documented to reduce sensitivity and specificity of mammography. However, little is known regarding the effect of normal background parenchymal enhancement on accuracy of breast MRI. The purpose of this study was to evaluate the effect of background parenchymal enhancement on MRI diagnostic performance.

Effects of lesion positioning on digital magnification mammography performance.

Rationale And Objectives: We undertook this study to determine whether differences in detector-lesion distance resulted in appreciable effects on digital magnification mammography performance as measured using the American College of Radiology (ACR) mammography phantom and a line pair test pattern.

Materials And Methods: Images of the standard 42-mm thick standard ACR mammography phantom with a wax insert on one side containing simulated fibers, calcifications, and masses were obtained on a Senographe Essential digital mammography system with the phantom in upright and inverted positions. The process was repeated with a line pair test pattern for measuring resolution.