Gurney

BACKGROUND: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent...

Career shifts are a naturally occurring part of the trauma and acute care surgeon's profession. These transitions may occur at various timepoints throughout a surgeon's career and each has their own specific challenges. Finding a good fit for your first job is critical for ensuring success as an early career surgeon. Equally, understanding how to navigate promotions or a change in job location mid-career can be fraught with uncertainty. As one progresses in their career, knowing when to take on a leadership position is oftentimes difficult as it may mean a change in priorities...

Polycyclic aromatic compounds (PACs) - a large group of organic chemicals naturally present in petroleum deposits (i.e., petrogenic) or released into the environment by incomplete combustion of organic materials (i.e., pyrogenic) - represent a potential risk to the health of aquatic ecosystems. In high latitude freshwater ecosystems, concentrations of PACs may be increasing, yet there are limited studies in such systems to assess change and to understand threats. Using 10 years of contemporary data from passive samplers deployed across five regions (n = 43 sites) in the Mackenzie River Basin, we (i) describe baseline levels of PACs, (ii) assess spatiotemporal patterns, and (ii) evaluate the extent to which environmental factors (fire, snowmelt, and proximity to oil infrastructure) influence concentrations in this system...

INTRODUCTION: New Zealand has a population of only 5.5 million meaning that for many surgical procedures the country qualifies as a "low-volume center." However, the health system is well developed and required to provide complex surgical procedures that benchmark internationally against comparable countries. This investigation was undertaken to review regional variation and volumes of complex resection and palliative upper gastrointestinal (UGI) surgical procedures within New Zealand...

People frequently face decisions that require making inferences about withheld information. The advent of large language models coupled with conversational technology, e.g., Alexa, Siri, Cortana, and the Google Assistant, is changing the mode in which people make these inferences. We demonstrate that conversational modes of information provision, relative to traditional digital media, result in more critical responses to withheld information, including: (1) a reduction in evaluations of a product or service for which information is withheld and (2) an increased likelihood of recalling that information was withheld...

Pectoralis major (PM) rupture is a rare injury, commonly misdiagnosed, that affects mostly young male athletes aged 20-40 years. This type of injury is typically associated with weight lifting, especially bench pressing. In an occupational medicine setting, it is extremely rare and not much reported in the literature. We present the case of a 30-year-old trauma technician male who presented with right shoulder and chest pain following a popping sensation while pushing in full momentum a patient on a gurney accidentally set on break mode...

Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified CCUS patients by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS...

Oncolytic viruses (OV) are part of a burgeoning field of investigational oncolytic therapy (OT), in which lytic viruses dissolve advanced tumors productively and specifically. One such OT is a Coxsackievirus A21 (CVA21) based OV that is currently under clinical evaluation. A tissue culture infectious dose (TCID50) assay was used for CVA21 potency release and stability testing in early clinical development. The titer measured in this method was an extrapolated value from cytopathic effect (CPE) observed during the serial dilution but doesn't represent direct viral killing of cells...

Recent interest in the biology and function of peritoneal tissue resident macrophages (pMΦ) has led to a better understanding of their cellular origin, programming and renewal. The programming of pMΦ is dependent on microenvironmental cues and tissue specific transcription factors, including GATA6. However, the contribution of microRNAs remains poorly defined. We conducted a detailed analysis of the impact of GATA6-deficiency on microRNA expression in mouse pMΦ. Our data suggest that for many of the pMΦ, microRNA composition may be established during tissue specialization, and that the effect of GATA6 knockout is largely unable to be rescued in the adult by exogenous GATA6...

BACKGROUND: Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC. METHODS: IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430)...

The vertebrate basal ganglia play an important role in action selection-the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of the neurotransmitter dopamine. We investigated reducing or increasing the tonic level of simulated dopamine in a prior model of the basal ganglia integrated into a robot control architecture engaged in a foraging task inspired by animal behaviour. The main findings were that progressive reductions in the levels of simulated dopamine caused slowed behaviour and, at low levels, an inability to initiate movement...

OBJECTIVES: The objective of this study is to investigate the influence of diabetes on breast cancer-specific survival among women with breast cancer in Aotearoa/New Zealand. METHODS: This study included women diagnosed with invasive breast cancer between 2005 and 2020, with their information documented in the Te Rēhita Mate Ūtaetae-Breast Cancer Foundation National Register. Breast cancer survival curves for women with diabetes and those without diabetes were generated using the Kaplan-Meier method...

BACKGROUND: Intravoxel incoherent motion (IVIM)-corrected diffusion tensor imaging (DTI) potentially enhances return-to-play (RTP) prediction after hamstring injuries. However, the long scan times hamper clinical implementation. We assessed accelerated IVIM-corrected DTI approaches in acute hamstring injuries and explore the sensitivity of the perfusion fraction (f) to acute muscle damage. METHODS: Athletes with acute hamstring injury received DTI scans of both thighs < 7 days after injury and at RTP...

People-centred care is foundational to healthcare excellence. One urban Canadian long-term care residence recently participated in an initiative titled "Improving the Care Conference Experience" to engage residents and families in annual care conferences. The Institute for Healthcare Improvement introduced "care bundles" to group evidence-based practices within standard processes. For this initiative, one health region's Experience in Care team co-developed, implemented and evaluated an "experience bundle" for inclusive care conferences with key stakeholders including residents, family members, direct care providers and leadership...

Chlorella supplementation is reported to improve V˙O2max following extended supplementation periods (~3 weeks). However, there is little research on its impact over submaximal exercise intensities and following shorter supplementation regimens. This study aimed to investigate the efficacy of 6 g/day 2-day chlorella supplementation on exercise performance in healthy young adults. Twenty young healthy adults (Males = 16, Females = 4) (Age 22 ± 6 years, V˙O2max 42.7 ± 9.6 mL/(kg·min)) were recruited for this double-blinded, randomised cross-over study...

INTRODUCTION: Mortality rates among hypotensive civilian patients requiring emergent laparotomy exceed 40%. Damage control (DCR) principles were incorporated into the military's Clinical Practice Guidelines (CPG) in 2008. We examined combat casualties requiring emergent laparotomy to characterize how mortality rates compare to hypotensive civilian trauma patients. METHODS: The DoD Trauma Registry (2004-2020) was queried for adults who underwent combat laparotomy...

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Peritoneal tissue-resident macrophages have broad functions in the maintenance of homeostasis and are involved in pathologies within local and neighboring tissues. Their functions are dictated by microenvironmental cues; thus, it is essential to investigate their behavior in an in vivo physiological niche. Currently, specific peritoneal macrophage-targeting methodologies employ whole-mouse transgenic models. Here, a protocol for effective in vivo modulation of mRNA and small RNA species (e.g., microRNA) expression in peritoneal macrophages using lentivirus particles is described...

BACKGROUND AND OBJECTIVE: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL). METHODS: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation...

BACKGROUND: Unintentional falls are common among the elderly and given the expected increase of the aging population, these falls contribute to a high number of admissions to the emergency department. Relatively low-energy trauma mechanisms can lead to serious injuries in the elderly, with contributing factors being comorbidities, medication use and degenerative abnormalities. CASE PRESENTATION: A 94-year-old female suffered an unintentional fall at home. Upon arrival of the ambulance at her house she was hemodynamically stable and mobilized to the gurney with assistance...