Young oncologists' perspective on the role and future of the clinician-scientist in oncology

Jóvenes oncólogos; OncologíaJoves oncòlegs; OncologiaYoung oncologists; OncologyThe clinician-scientist, or more commonly known as physician-scientist in North America, covers a wide spectrum of roles, but is essentially an individual who holds a medical degree and usually a postgraduate scientific qualification (e.g. MS/MSc/MRes and PhD) and is primarily dedicated to pursuing their academic research interests, which can range from basic science to more translational or clinical research. Clinician-scientists are important players within the contemporary multidisciplinary and interprofessional teamscience approach to cancer research and cancer care. Clinical experience alongside rigorous training in research and scientific methodologies provides a strong foundation for clinician-scientists to conduct and lead research advancing the way we understand and treat patients with cancer.European Society for Medical Oncology (ESMO) (no grant number)

Cardiovascular effects of intravenous vatinoxan in wild boars (Sus scrofa) anaesthetised with intramuscular medetomidine-tiletamine-zolazepam

Background The potent sedative medetomidine is a commonly used adjunct for the immobilisation of non-domestic mammals. However, its use is associated with pronounced cardiovascular side effects, such as bradycardia, vasoconstriction and decreased cardiac output. We investigated the effects of the peripherally-acting alpha-2-adrenoceptor antagonist vatinoxan on cardiovascular properties in medetomidine-tiletamine-zolazepam anaesthetised wild boar (Sus scrofa). Methods Twelve wild boars, anaesthetised twice with medetomidine (0.1 mg/kg) and tiletamine/zolazepam (2.5 mg/kg) IM in a randomised, crossover study, were administered (0.1 mg/kg) vatinoxan or an equivalent volume of saline IV (control). Cardiovascular variables, including heart rate (HR), mean arterial blood pressure (MAP), pulmonary artery pressure (PAP), pulmonary artery occlusion pressure (PAOP) and cardiac output (CO), were assessed 5 min prior to vatinoxan/saline administration until the end of anaesthesia 30 min later. Results MAP (p < 0.0001), MPAP (p < 0.001) and MPAOP (p < 0.0001) significantly decreased from baseline after vatinoxan until the end of anaesthesia. HR increased significantly (p < 0.0001) from baseline after vatinoxan administration. However, the effect on HR subsided 3 min after vatinoxan. All variables remained constant after saline injection. There was no significant effect of vatinoxan or saline on CO. Conclusion Vatinoxan significantly reduced systemic and pulmonary artery hypertension, induced by medetomidine in wild boar.Peer reviewe

Ampakine CX1942 attenuates opioid-induced respiratory depression and corrects the hypoxaemic effects of etorphine in immobilized goats (Capra hircus)

OBJECTIVES : To determine whether CX1942 reverses respiratory depression in etorphineimmobilized goats, and to compare its effects with those of doxapram hydrochloride. STUDY DESIGN : A prospective, crossover experimental trial conducted at 1753 m.a.s.l. ANIMALS : Eight adult female Boer goats (Capra hircus) with a mean ± standard deviationmass of 27.1 ± 1.6 kg. METHODS : Following immobilization with 0.1 mg kg−1 etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials. Respiratory rate, ventilation and tidal volume were measured continuously. Arterial blood samples for the determination of PaO2, PaCO2, pH and SaO2 were taken 2 minutes before and then at 5 minute intervals after drug administration for 25 minutes. RESULTS : Doxapram corrected etorphine-induced respiratory depression but also led to arousal and hyperventilation at 2 minutes after its administration, as indicated by the low PaCO2 (27.8 ± 4.5 mmHg) and ventilation of 5.32 ± 5.24 L minute−1 above pre-immobilization values. CX1942 improved respiratory parameters and corrected etorphine's hypoxaemic effects more gradually than did doxapram, with a more sustained improvement in PaO2 and SaO2 in comparison with the control trial. CONCLUSIONS : CX1942 attenuated opioid-induced respiratory depression and corrected the hypoxaemic effects of etorphine in immobilized goats. CLINICAL RELEVANCE : Ampakines potentially offer advantages over doxapram, a conventional treatment, in reversing etorphine-induced respiratory depression without causing unwanted side effects, particularly arousal, in immobilized animals.A Faculty Research Committee Grant, University of the Witwatersrand, awarded to AJH, and a Thuthuka grant from the National Research Foundation, South Africa, awarded to LCRM.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1467-29952017-09-30hb2017Paraclinical Science

Use of butorphanol and diprenorphine to counter respiratory impairment in the immobilised white rhinoceros (Ceratotherium simum)

Opioid-induced immobilisation results in severe respiratory impairment in the white rhinoceros. It has therefore been attempted in the field to reverse this impairment with the use of opioid agonist-antagonists, such as nalorphine, nalbuphine, butorphanol and diprenorphine; however, the efficacy of some of these treatments has yet to be determined. The efficacy of butorphanol, either alone or in combination with diprenorphine both with and without oxygen insufflation, in alleviating opioid-induced respiratory impairment was evaluated. The study was performed in two parts: a boma trial and a field trial. Rhinoceroses were immobilised specifically for the study, according to a strict protocol to minimise confounding variables. A two-way analysis of variance was used to compare the physiological responses of the rhinoceroses to the different treatments and their effects over time. The intravenous administration of butorphanol (at 3.3 mg per mg etorphine) plus diprenorphine (at 0.4 mg per mg etorphine) did not offer any advantage over butorphanol (at 15 mg per mg etorphine) alone with regard to improving PaO2, PaCO2 and respiratory rates in etorphine-immobilised white rhinoceroses. Both butorphanol + diprenorphine + oxygen and butorphanol + oxygen, at the doses used, significantly improved the etorphine-induced hypoxaemia in both boma- and field-immobilised white rhinoceroses. Clinically acceptable oxygenation in field-immobilised white rhinoceroses can be achieved by using either treatment regimen, provided that it is combined with oxygen insufflation

Investigation of cardiorespiratory effects of the selective 5-HT4 agonist BIMU-8 in etorphine-immobilised goats (Capra aegagrus hircus) in a randomized, blinded and controlled trial

BACKGROUND : Opioid-induced respiratory compromise remains a significant challenge in etorphine-immobilised wildlife. Serotonergic agonists offer a potential avenue for preventing or treating opioid-induced respiratory compromise. We therefore aimed to determine whether the selective 5- hydroxytryptamine receptor 4 (5-HT4) agonist, BIMU-8, reverses opioidinduced respiratory compromise in etorphine-immobilised goats. METHODS : Seven healthy adult goats were immobilised with etorphine, then treated with BIMU-8 or sterile water 5 minutes later in a randomised, prospective cross-over study. Cardiorespiratory variables were measured at 1-minute intervals from 4 minutes before etorphine to 15 minutes after its administration. Arterial blood gas analyses were also performed before and after etorphine administration and the respective treatments. RESULTS : Intravenous injection of BIMU-8 attenuated etorphine-induced respiratory compromise, as indicated by improvements, compared to baseline and between treatments, in respiratory rate (ƒR), peripheral arterial blood oxygen saturation (SpO2), partial pressure of arterial oxygen (PaO2) and the alveolar-arterial oxygen partial pressure gradient (P(A-a)O2). BIMU-8 caused an increase in heart rate and a temporary decrease in arterial blood pressure. Mild movements and slight muscle spasm occurred but BIMU-8 did not reverse immobilisation. CONCLUSION : Our results indicate that BIMU-8 may be a potential drug candidate for the treatment, or prevention, of etorphine-induced respiratory compromise in immobilised ungulateshttps://bvajournals.onlinelibrary.wiley.com/journal/20427670dm2022Centre for Veterinary Wildlife StudiesParaclinical Science

A structure-function analysis of the left ventricle

This study presents a structure-function analysis of the mammalian left ventricle and examines the performance of the cardiac capillary network, mitochondria, and myofibrils at rest and during simulated heavy exercise. Left ventricular external mechanical work rate was calculated from cardiac output and systemic mean arterial blood pressure in resting sheep (Ovis aries; n = 4) and goats (Capra hircus; n = 4) under mild sedation, followed by perfusion-fixation of the left ventricle and quantification of the cardiac capillary-tissue geometry and cardiomyocyte ultrastructure. The investigation was then extended to heavy exercise by increasing cardiac work according to published hemodynamics of sheep and goats performing sustained treadmill exercise. Left ventricular work rate averaged 0.017 W/cm3 of tissue at rest and was estimated to increase to ∼0.060 W/cm3 during heavy exercise. According to an oxygen transport model we applied to the left ventricular tissue, we predicted that oxygen consumption increases from 195 nmol O2·s-1·cm-3 of tissue at rest to ∼600 nmol O2·s-1·cm-3 during heavy exercise, which is within 90% of the oxygen demand rate and consistent with work remaining predominantly aerobic. Mitochondria represent 21-22% of cardiomyocyte volume and consume oxygen at a rate of 1,150 nmol O2·s-1·cm-3 of mitochondria at rest and ∼3,600 nmol O2·s-1·cm-3 during heavy exercise, which is within 80% of maximum in vitro rates and consistent with mitochondria operating near their functional limits. Myofibrils represent 65-66% of cardiomyocyte volume, and according to a Laplacian model of the left ventricular chamber, generate peak fiber tensions in the range of 50 to 70 kPa at rest and during heavy exercise, which is less than maximum tension of isolated cardiac tissue (120-140 kPa) and is explained by an apparent reserve capacity for tension development built into the left ventricle.This research was supported by an Australian Research Council Discovery Project Award to R. S. Seymour, S. K. Maloney, and A. P. Farrell (DP-120102081). E. P. Snelling holds a South African Claude Leon Foundation Postdoctoral Fellowship. J. E. F. Green is supported by an Australian Research Council Discovery Early Career Researcher Award (DE- 130100031). A. P. Farrell holds a Canada Research Chair and is supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada.http://jap.physiology.org2017-10-31hb2017Paraclinical Science

Safety and efficacy of an attenuated heartwater (Ehrlichia ruminantium) vaccine administered by the intramuscular route in cattle, sheep and Angora goats

Please read abstract in the article.Red Meat Research and Development Trust of South Africa; Mohair South Africa LTD; Technology Innovation Agency, South Africa; Agricultural Research Council, South Africa.http://www.elsevier.com/locate/vaccinehj2021Veterinary Tropical Disease

CRIB—the use of cardiac rehabilitation services to aid the recovery of patients with bowel cancer: a pilot randomised controlled trial (RCT) with embedded feasibility study

Introduction: Patients with colorectal cancer report ongoing physical and psychological impairments and a high proportion of these patients are overweight, insufficiently active and high-risk drinkers, putting them at risk of poor recovery and risk of recurrence and comorbidities. A challenge is implementing sustainable and effective rehabilitation as part of routine care for this group.Methods and analysis: A two-arm pilot randomised controlled trial (RCT) with embedded feasibility study undertaken as a phased programme of work. The intervention involves an existing cardiac rehabilitation programme for cardiac patients accepting colorectal cancer patient referrals. The intervention consists of supervised exercise sessions run by a cardiac physiotherapist and information sessions. Phase 1 will involve one research site enrolling 12 patients to assess intervention and study design processes. Semistructured interviews with patients with colorectal cancer and cardiac patients and clinicians will be used to gather data on acceptability of the intervention and study procedures. Phase 2 will involve three sites enrolling 66 patients with colorectal cancer randomised to control or intervention groups. Outcome measures will be taken preintervention and postintervention, for phases 1 and 2. The primary outcome is accelerometer measured physical activity; secondary outcomes are self-report physical activity, quality of life, anxiety, depression, symptoms including fatigue. The following variables will also be examined to determine if these factors influence adherence and outcomes: self-efficacy, risk perception and treatments.Ethics and dissemination: Full ethical approval was granted by NRES Committees—North of Scotland (13/NS/0004; IRAS project ID: 121757) on 22 February 2013. The proposed work is novel in that it aims to test the feasibility and acceptability of using an evidence-based and theory driven existing cardiac rehabilitation service with patients with colorectal cancer. Should this model of rehabilitation prove to be clinically and cost effective we aim to conduct a randomised controlled trial of this intervention to measure effectiveness.Trial registration reference ISRCTN63510637; UKCRN id 14092