Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.

Role of remediation in cases of serious misconduct before UK healthcare regulators: a qualitative study.

Background: The raison d'etre of healthcare profession regulators across the globe is to protect patients and the public from the risk of harm. In cases of serious misconduct, remediation is deemed to be an important factor when considering the risk of harm from a practitioner under investigation. Yet, we know very little about how regulators account for remediation in their decision-making, and whether it is consistent with the aim of risk reduction.

Scaling up area-based conservation to implement the Global Biodiversity Framework's 30x30 target: The role of Nature's Strongholds.

The Global Biodiversity Framework (GBF), signed in 2022 by Parties to the Convention on Biological Diversity, recognized the importance of area-based conservation, and its goals and targets specify the characteristics of protected and conserved areas (PCAs) that disproportionately contribute to biodiversity conservation. To achieve the GBF's target of conserving a global area of 30% by 2030, this Essay argues for recognizing these characteristics and scaling them up through the conservation of areas that are: extensive (typically larger than 5,000 km2); have interconnected PCAs (either physically or as part of a jurisdictional network, and frequently embedded in larger conservation landscapes); have high ecological integrity; and are effectively managed and equitably governed. These areas are presented as "Nature's Strongholds," illustrated by examples from the Congo and Amazon basins.

Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency.

Dysregulated lipid homeostasis is emerging as a potential cause of neurodegenerative disorders. However, evidence of errors in lipid homeostasis as a pathogenic mechanism of neurodegeneration remains limited. Here, we show that cerebellar neurodegeneration caused by Sorting Nexin 14 (SNX14) deficiency is associated with lipid homeostasis defects.

Factors associated with weight loss and health gains in a structured lifestyle modification programme for adults with severe obesity: a prospective cohort study.

Background: Individual responses to behavioural weight loss interventions can vary significantly, and a better understanding of the factors associated with successful treatment might help to target interventions for those who will benefit the most. We sought to identify demographic and clinical characteristics that predicted intervention "success" (defined as ≥5% weight loss) and other health gains in patients with severe obesity attending a ten-week structured lifestyle modification programme.

Methods: We conducted a prospective cohort study of all 1122 patients (751 (66.

Audit, Feedback, and Education to Improve Quality and Outcomes in Transurethral Resection and Single-Instillation Intravesical Chemotherapy for Nonmuscle Invasive Bladder Cancer Treatment: Protocol for a Multicenter International Observational Study With an Embedded Cluster Randomized Trial.

Background: Nonmuscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancers. It is common and costly. Cost and detriment to patient outcomes and quality of life are driven by high recurrence rates and the need for regular invasive surveillance and repeat treatments.

Protocol for a MULTI-centre feasibility study to assess the use of Tc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study).

Introduction: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding.

Epidemiology of Renal Cell Carcinoma: 2022 Update.

Context: International variations in the rates of kidney cancer (KC) are considerable. An understanding of the risk factors for KC development is necessary to generate opportunities to reduce its incidence through prevention and surveillance.

Objective: To retrieve and summarize global incidence and mortality rates of KC and risk factors associated with its development, and to describe known familial syndromes and genetic alterations that represent biologic risk factors.

Perioperative management including dual cell salvage in a Jehovah's Witness patient undergoing major urological surgery.

Complex surgery associated with major hemorrhage presents particular risks for Jehovah's Witnesses who do not accept transfusion of blood products. Intraoperative use of two cell saver machines simultaneously can maximize the yield of salvaged blood from both the operative field and from washed surgical swabs and can potentially be life-saving.

Publishing Individual Surgeons' Outcomes in Urology: Empowering Patient Choice and Improving Safety.

It has been demonstrated that publication of individual surgeons' outcomes has improved patient safety and choice. Taking into consideration the lack of negative impact on patient selection and surgical training, it is difficult to argue that surgeons' outcomes should not be openly available in urology.

Selection of metastasis competent subclones in the tumour interior.

The genetic evolutionary features of solid tumour growth are becoming increasingly well described, but the spatial and physical nature of subclonal growth remains unclear. Here, we utilize 102 macroscopic whole-tumour images from clear cell renal cell carcinoma patients, with matched genetic and phenotypic data from 756 biopsies. Utilizing a digital image processing pipeline, a renal pathologist marked the boundaries between tumour and normal tissue and extracted positions of boundary line and biopsy regions to X and Y coordinates.

The Impact of the COVID-19 Pandemic on Genitourinary Cancer Care: Re-envisioning the Future.

Context: The coronavirus disease 2019 (COVID-19) pandemic necessitated rapid changes in medical practice. Many of these changes may add value to care, creating opportunities going forward.

Objective: To provide an evidence-informed, expert-derived review of genitourinary cancer care moving forward following the initial COVID-19 pandemic.

Numerical simulation modeling of the irreversible electroporation treatment zone for focal therapy of prostate cancer, correlation with whole-mount pathology and T2-weighted MRI sequences.

Background: At present, it is not possible to predict the ablation zone volume following irreversible electroporation (IRE) for prostate cancer (PCa). This study aimed to determine the necessary electrical field threshold to ablate human prostate tissue with IRE.

Methods: In this prospective multicenter trial, patients with localized PCa were treated with IRE 4 weeks before their scheduled radical prostatectomy.

Surgery for high-risk locally advanced (pT3c) renal tumours: oncological outcomes and prognostic significance of a modified International Metastatic Renal Cell Cancer Database Consortium (IMDC) score.

Objectives: To evaluate contemporary oncological outcomes and long-term survival in patients undergoing surgery for urological tumours involving the peridiaphragmatic inferior vena cava up to the level of the right atrium. To apply prognostic factors developed for metastatic renal cancer to patients with very-high-risk but apparently localized tumours, and develop a scoring system.

Patients And Methods: A retrospective cohort study of 54 patients referred between December 2007 and April 2018 to a single surgical and oncological team was conducted.

The Case for Photodynamic Diagnosis-assisted Resection Without Intravesical Single-shot Chemotherapy.

Although there is level 1 evidence for the use of intravesical chemotherapy after the transurethral resection of bladder tumour, the decision to apply it needs to be individualised. "What benefit will the patient derive from it?"

The natural history of crouch gait in bilateral cerebral palsy: A systematic review.

Aim: To systematically review the natural history of crouch gait in bilateral cerebral palsy (CP) in the absence of surgical intervention and to review any relationship between clinical variables and progression of knee crouch.

Methods: Relevant literature was identified by searching article databases (PubMed, CINAHL, EMBASE, and Web of Science). Included studies reported on participants with bilateral CP who had 3-dimensional gait analysis on at least two occasions with no surgical interventions between analyses.

Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.

Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters.

Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal.

Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening.