Biopsy-based Basal-luminal Subtyping Classifier in High-risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials.

Background And Objective: Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful.

cAMP driven UCP1 induction in human adipocytes requires ATGL-catalyzed lipolysis.

Objective: The uncoupling protein 1 (UCP1) is induced in brown or "beige" adipocytes through catecholamine-induced cAMP signaling, which activates diverse transcription factors. UCP1 expression can also be enhanced by PPARγ agonists such as rosiglitazone (Rsg). However, it is unclear whether this upregulation results from de-novo differentiation of beige adipocytes from progenitor cells, or from the induction of UCP1 in pre-existing adipocytes.

PPARγ activation by lipolysis-generated ligands is required for cAMP dependent induction in human thermogenic adipocytes.

Objective: The uncoupling protein 1 (UCP1) is induced in brown or "beige" adipocytes through catecholamine-induced cAMP signaling, which activates diverse transcription factors. UCP1 expression can also be enhanced by PPARγ agonists such as rosiglitazone (Rsg). However, it is unclear whether this upregulation results from de-novo differentiation of beige adipocytes from progenitor cells, or from the induction of UCP1 in pre-existing adipocytes.

Modes of failure of guide catheter extensions: Insights from the MAUDE database.

Objectives: Guide catheter extensions (GCEs) are commonly used to facilitate percutaneous coronary interventions (PCIs). We investigated the incidence and modes of failure of GCEs..

Regulation of lipolysis by 14-3-3 proteins on human adipocyte lipid droplets.

Adipocyte lipid droplets (LDs) play a crucial role in systemic lipid metabolism by storing and releasing lipids to meet the organism's energy needs. Hormonal signals such as catecholamines and insulin act on adipocyte LDs, and impaired responsiveness to these signals can lead to uncontrolled lipolysis, lipotoxicity, and metabolic disease. To investigate the mechanisms that control LD function in human adipocytes, we applied proximity labeling mediated by enhanced ascorbate peroxidase (APEX2) to identify the interactome of PLIN1 in adipocytes differentiated from human mesenchymal progenitor cells.

A distinct class of hematopoietic stem cells develop from the human yellow bone marrow.

Aging and metabolic diseases are accompanied by systemic inflammation, but the mechanisms that induce this state are not known. We developed a human bone-marrow organoid system to explore mechanisms underlying metabolic-disease associated systemic inflammation. We find that a distinct type of hematopoietic stem cell (HSC) develops in the adipose-rich, yellow bone marrow, which is known to gradually replace the hematopoietic red marrow as we age and during metabolic disease.

Wnt signaling preserves progenitor cell multipotency during adipose tissue development.

Mesenchymal stem/progenitor cells are essential for tissue development and repair throughout life, but how they are maintained under chronic differentiation pressure is not known. Using single-cell transcriptomics of human progenitor cells we find that adipose differentiation stimuli elicit two cellular trajectories: one toward mature adipocytes and another toward a pool of non-differentiated cells that maintain progenitor characteristics. These cells are induced by transient Wnt pathway activation and express numerous extracellular matrix genes and are therefore named structural Wnt-regulated adipose tissue cells.

Stereotactic Radiosurgery vs Conventional Radiotherapy for Localized Vertebral Metastases of the Spine: Phase 3 Results of NRG Oncology/RTOG 0631 Randomized Clinical Trial.

Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control.

Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases.

Design, Setting, And Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups.

Neighborhood Deprivation and Rurality Associated With Patient-Reported Outcomes and Survival in Men With Prostate Cancer in NRG Oncology RTOG 0415.

Purpose: Rurality and neighborhood deprivation can contribute to poor patient-reported outcomes, which have not been systematically evaluated in patients with specific cancers in national trials. Our objective was to examine the effect of rurality and neighborhood socioeconomic and environmental deprivation on patient-reported outcomes and survival in men with prostate cancer in NRG Oncology RTOG 0415.

Methods And Materials: Data from men with prostate cancer in trial NRG Oncology RTOG 0415 were analyzed; 1,092 men were randomized to receive conventional radiation therapy or hypofractionated radiation therapy.

Analysis of a Biopsy-Based Genomic Classifier in High-Risk Prostate Cancer: Meta-Analysis of the NRG Oncology/Radiation Therapy Oncology Group 9202, 9413, and 9902 Phase 3 Randomized Trials.

Purpose: Decipher is a genomic classifier (GC) prospectively validated postprostatectomy. We validated the performance of the GC in pretreatment biopsy samples within the context of 3 randomized phase 3 high-risk definitive radiation therapy trials.

Methods And Materials: A prespecified analysis plan (NRG-GU-TS006) was approved to obtain formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled in the NRG/Radiation Therapy Oncology Group (RTOG) 9202, 9413, and 9902 phase 3 randomized trials.

A neurogenic signature involving monoamine Oxidase-A controls human thermogenic adipose tissue development.

Mechanisms that control 'beige/brite' thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin.

CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease.

Obesity and type 2 diabetes are associated with disturbances in insulin-regulated glucose and lipid fluxes and severe comorbidities including cardiovascular disease and steatohepatitis. Whole body metabolism is regulated by lipid-storing white adipocytes as well as "brown" and "brite/beige" adipocytes that express thermogenic uncoupling protein 1 (UCP1) and secrete factors favorable to metabolic health. Implantation of brown fat into obese mice improves glucose tolerance, but translation to humans has been stymied by low abundance of primary human beige adipocytes.

Staphylococcal Scalded Skin Syndrome and Bullous Impetigo.

Staphylococcal scalded skin syndrome (SSSS) and bullous impetigo are infections caused by . The pathogenesis of both conditions centers around exotoxin mediated cleavage of desmoglein-1, which results in intraepidermal desquamation. Bullous impetigo is due to the local release of these toxins and thus, often presents with localized skin findings, whereas SSSS is from the systemic spread of these toxins, resulting in a more generalized rash and severe presentation.

A Rare Iatrogenic Trio: Pneumopericardium, Pneumoperitoneum, and Pericarditis.

We present a rare case of iatrogenic pneumopericardium, pneumoperitoneum, and pericarditis after emergency pericardiocentesis for pericardial tamponade. The patient had profound bowel distention at the time of the procedure that led to iatrogenic pericardioperitoneal fistula formation along with transverse colon perforation, which manifested later after pericardial drain removal. This condition required repeat pericardiocentesis, laparoscopic colon repair, a long course of antibiotics, and an eventual pericardial window.

Feasibility of Transcatheter Mitral Valve Repair for Non-A2P2 Mitral Regurgitation.

MitraClip is approved for treatment of both degenerative and functional mitral regurgitation (MR). The landmark trials for this device included only patients with A2P2 location of MR. Initial commercial experience showed A2P2 location was associated with higher technical success as compared with non-A2P2 location.

Haemodynamic Interplay Between Concomitant Left Ventricular Outflow Tract Obstruction and Aortic Stenosis.

The authors describe a patient with hypertrophic cardiomyopathy with concomitant left ventricular outflow tract obstruction and aortic stenosis. Detailed haemodynamic assessment of the serial lesions was performed. Alcohol septal ablation resulted in a significant reduction of gradients across the left ventricular outflow tract.

Photographic Confirmation of Biopsy Sites Saves Lives.

Quality photographic documentation of lesions prior to biopsy can decrease the risk of wrong site surgery, improve patient care, and save lives.

The transseptal puncture experience: Safety insights from FDA MAUDE database.

Background: There is a paucity of literature on safety and efficacy of various transseptal puncture (TSP) needles.

Objectives: To assess the reported mechanisms of failure, complications, and outcomes among the most frequently used transseptal needles in the United States.

Methods: We queried the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database between January 2011 and January 2021 for reports on the most commonly used transseptal needles: NRG (Baylis Medical, Montreal, Canada), and BRK (St.

Asymptomatic degenerative mitral regurgitation repair: Validating guidelines for early intervention.

Introduction: Mitral repair for asymptomatic (New York Heart Association [NYHA] class I) degenerative mitral regurgitation (MR) is supported by the guidelines, but is not performed often. We sought to determine outcomes for asymptomatic patients when compared with those with symptoms.

Methods: Between 2004 and 2018, 1027 patients underwent mitral replacement (22) or repair with or without other cardiac surgery (1005), the latter being grouped by NYHA class: I (n = 470; 47%), II (n = 408; 40%), or III/IV (n = 127; 13%).

Robotic Transthoracic Repair of a Right-Sided Traumatic Diaphragmatic Rupture.

 Traumatic diaphragm rupture injury repairs are predominately performed through thoracotomy, laparotomy, or a combination of the two approaches. While open surgery is often necessary to follow the fundamentals of damage-control operations in unstable or polytrauma patients, minimally invasive surgery may be an alternative for those with a low injury burden to reduce the postoperative morbidities associated with open operations.  We describe the first case of a right-sided diaphragm rupture from blunt trauma that was repaired by a robotic transthoracic approach in the index admission.

Erythema ab igne with features resembling keratosis lichenoides chronica.

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low-grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable.

Human thermogenic adipocyte regulation by the long noncoding RNA LINC00473.

Human thermogenic adipose tissue mitigates metabolic disease, raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long non-coding RNA, which is highly correlated with UCP1 expression and decreased in obesity and type-2 diabetes. is detected in progenitor cells, and increases upon differentiation and in response to cAMP.

Use of the Burden of Diabetes Mellitus Score for Cardiovascular Disease Risk Assessment.

Uncontrolled type II diabetes mellitus (DM) using single point hemoglobin A1c levels has been associated with poor cardiovascular outcomes. However, methods to quantify the effect of uncontrolled DM over time have been inconsistent. To quantify hyperglycemia over time and assess its cardiovascular effects we developed and tested a DM burden score which accounts for time in years prior to DM diagnosis, diagnostic HbA1c, and aggregate HbA1c levels thereafter.

Concomitant atrial fibrillation ablation in patients undergoing coronary artery bypass and cardiac valve surgery.

Surgical ablation of atrial fibrillation (AF) in conjunction with other cardiac surgery is now a class I guideline recommendation. Multiple studies have demonstrated that the concomitant surgical ablation of AF can be performed safely and effectively during valve and coronary artery bypass grafting (CABG) resulting in a return to sinus rhythm postoperatively and improved long-term results. However, the surgical ablation of AF at the time of other cardiac surgery is performed less often than it should be, especially in patients undergoing CABG and aortic valve surgery.