PALLIATION AND LIFE QUALITY IN LUNG-CANCER - HOW GOOD ARE CLINICIAN AT JUDGING TREATMENT OUTCOME

A recent trial by the MRC Lung Cancer Working Party used physician assessments to compare two palliative schedules of radiotherapy in lung cancer. A prospective study has been undertaken on a subset of these trial patients to see how physician assessments of symptomatic relief and general condition correlate with patient perception of therapeutic response. In 40 patients followed up monthly from presentation until close to death, good agreement was found between doctors and patients on change in specific physical symptoms and overall physical condition. Doctors were poor judges of life quality at presentation but appeared able to identify relative improvement or deterioration in overall quality of life. In conclusion, physician assessments may constitute valid end-points for radiotherapy trials comparing palliative schedules in lung cance

Repeated ischaemic preconditioning: A novel therapeutic intervention and potential underlying mechanisms.

Ischaemic preconditioning (IPC) refers to the phenomenon that short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeatedly exposing tissue to IPC may increase the "dose" of protection, and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic (e.g. hormones, cytokines, blood-borne substances) stimuli, which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebro-vascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and attenuation of their consequences. We provide an overview of the literature pertaining to the impact of repeated IPC on cardiovascular function, related to both local and or remote adaptation, as well as potential clinical implications. This article is protected by copyright. All rights reserved

Inference of tissue haemoglobin concentration from Stereo RGB

Multispectral imaging (MSI) can provide information about tissue oxygenation, perfusion and potentially function during surgery. In this paper we present a novel, near real-time technique for intrinsic measurements of total haemoglobin (THb) and blood oxygenation (SO 22 ) in tissue using only RGB images from a stereo laparoscope. The high degree of spectral overlap between channels makes inference of haemoglobin concentration challenging, non-linear and under constrained. We decompose the problem into two constrained linear sub-problems and show that with Tikhonov regularisation the estimation significantly improves, giving robust estimation of the THb. We demonstrate by using the co-registered stereo image data from two cameras it is possible to get robust SO 22 estimation as well. Our method is closed from, providing computational efficiency even with multiple cameras. The method we present requires only spectral response calibration of each camera, without modification of existing laparoscopic imaging hardware. We validate our technique on synthetic data from Monte Carlo simulation and further, in vivo, on a multispectral porcine data set

Thermoregulatory responses to combined moderate heat stress and hypoxia

Objective: The aim of this study was to examine the cutaneous vascular and sudomotor responses to combined moderate passive heat stress and normobaric hypoxia. Method: Thirteen healthy young males, dressed in a water-perfused suit, underwent passive heating (Δcore temperature ~0.7 °C) twice (NORMOXIA; 20.9% O2 and HYPOXIA; 13% O2). Chest and forearm skin blood flow (SkBF; laser Doppler flux), local sweat rate (SR; capacitance hygrometry) and core (intestinal pill) and skin temperatures, were recorded. Results: HYPOXIA reduced baseline oxygen saturation (98±1 vs. 89±6%, P<0.001) and elevated chest (P=0.03) and forearm SkBF (P=0.03) and HR (64±9 vs. 69±8 beats.min-1, P<0.01). During heating, mean body temperature (T ̅BODY) thresholds for SkBF (P=0.41) and SR (P=0.28) elevations were not different between trials. The SkBF: T ̅BODY linear sensitivity during the initial phase of heating was lower at the Chest (P=0.035) but not different at the forearm (P=0.17) during HYPOXIA. With increasing levels of heating chest SkBF was not different (P=0.55) but forearm SkBF was lower on the forearm (P<0.01) during HYPOXIA. Chest (P=0.85) and forearm (P=0.79) SR:T ̅BODY linear sensitivities were not different between trials. Conclusion: Whilst sudomotor responses and the initiation of cutaneous blood flow elevations are unaffected, hypoxia differentially effects regional SkBF responses during moderate passive heating

Surgical spectral imaging

Recent technological developments have resulted in the availability of miniaturised spectral imaging sensors capable of operating in the multi- (MSI) and hyperspectral imaging (HSI) regimes. Simultaneous advances in image-processing techniques and artificial intelligence (AI), especially in machine learning and deep learning, have made these data-rich modalities highly attractive as a means of extracting biological information non-destructively. Surgery in particular is poised to benefit from this, as spectrally-resolved tissue optical properties can offer enhanced contrast as well as diagnostic and guidance information during interventions. This is particularly relevant for procedures where inherent contrast is low under standard white light visualisation. This review summarises recent work in surgical spectral imaging (SSI) techniques, taken from Pubmed, Google Scholar and arXiv searches spanning the period 2013–2019. New hardware, optimised for use in both open and minimally-invasive surgery (MIS), is described, and recent commercial activity is summarised. Computational approaches to extract spectral information from conventional colour images are reviewed, as tip-mounted cameras become more commonplace in MIS. Model-based and machine learning methods of data analysis are discussed in addition to simulation, phantom and clinical validation experiments. A wide variety of surgical pilot studies are reported but it is apparent that further work is needed to quantify the clinical value of MSI/HSI. The current trend toward data-driven analysis emphasises the importance of widely-available, standardised spectral imaging datasets, which will aid understanding of variability across organs and patients, and drive clinical translation

Historical reviews of the assessment of human cardiovascular function: interrogation and understanding of the control of skin blood flow.

Several techniques exist for the determination of skin blood flow that have historically been used in the investigation of thermoregulatory control of skin blood flow, and more recently, in clinical assessments or as an index of global vascular function. Skin blood flow measurement techniques differ in their methodology and their strengths and limitations. To examine the historical development of techniques for assessing skin blood flow by describing the origin, basic principles, and important aspects of each procedure and to provide recommendations for best practise. Venous occlusion plethysmography was one of the earliest techniques to intermittently index a limb's skin blood flow under conditions in which local muscle blood flow does not change. The introduction of laser Doppler flowmetry provided a method that continuously records an index of skin blood flow (red cell flux) (albeit from a relatively small skin area) that requires normalisation due to high site-to-site variability. The subsequent development of laser Doppler and laser speckle imaging techniques allows the mapping of skin blood flow from larger surface areas and the visualisation of capillary filling from the dermal plexus in two dimensions. The use of iontophoresis or intradermal microdialysis in conjunction with laser Doppler methods allows for the local delivery of pharmacological agents to interrogate the local and neural control of skin blood flow. The recent development of optical coherence tomography promises further advances in assessment of the skin circulation via three-dimensional imaging of the skin microvasculature for quantification of vessel diameter and vessel recruitment

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Background Ischaemic preconditioning has well-established cardiac and vascular protective effects. Short interventions (one week) of daily ischaemic preconditioning episodes improve conduit and microcirculatory function. This study examined whether a longer (eight weeks) and less frequent (three per week) protocol of repeated ischaemic preconditioning improves vascular function. Methods Eighteen males were randomly allocated to either ischaemic preconditioning (22.4 ± 2.3 years, 23.7 ± 3.1 kg/m2) or a control intervention (26.0 ± 4.8 years, 26.4 ± 1.9 kg/m2). Brachial artery endothelial-dependent (FMD), forearm cutaneous microvascular function and cardiorespiratory fitness were assessed at zero, two and eight weeks. Results A greater improvement in FMD was evident following ischaemic preconditioning training compared with control at weeks 2 (2.24% (0.40, 4.08); p=0.02) and 8 (1.11% (0.13, 2.10); p=0.03). Repeated ischaemic preconditioning did not change cutaneous microcirculatory function or fitness. Conclusions These data indicate that a feasible and practical protocol of regular ischaemic preconditioning episodes improves endothelial function in healthy individuals within two weeks, and these effects persist following repeated ischaemic preconditioning for eight weeks

REPEATED WARM WATER IMMERSION INDUCES SIMILAR CEREBROVASCULAR ADAPTATIONS TO 8-WEEKS OF MODERATE-INTENSITY EXERCISE TRAINING IN FEMALES

Exercise training has potential to positively impact cerebrovascular function in healthy and diseased individuals. Passive heat training using warm water immersion has recently been shown to enhance systemic vascular function including the cerebrovascular response to heating. We suggest that a passive heating intervention can be a useful adjunct or alternative to exercise training. Our aim was to directly compare the effects of exercise with warm water immersion training on cerebrovascular and thermoregulatory function. 18 females (25±5y) performed 8-weeks of moderate-intensity cycling (70% HRmax) or warm-water immersion (42°C) for 30 min three times per week. Brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness were measured prior to and following both interventions. A passive heat stress was employed to obtain temperature thresholds (Tb) and sensitivities for chest and forearm sweat rate (SR) and cutaneous vasodilation (CVC). Middle cerebral artery velocity (MCAv) was measured at rest and throughout heat stress. FMD (P=0.003) and VO2peak (P<0.001) improved following both interventions. MCAv and cerebrovascular conductance were higher at rest (P<0.001 and 0.05, respectively) and during passive heating (P<0.001 and <0.001, respectively) following both interventions. Chest and forearm SR occurred at a lower Tb post-intervention with no difference between interventions. Chest and forearm SR sensitivity were increased after both interventions with no differences between interventions at the forearm but a larger increase at the chest (P<0.001) following water immersion compared to exercise training. Chest and forearm CVC occurred at a lower Tb (P<0.001) following both interventions with no differences between interventions or over time. Warm water immersion training elicits favourable and similar cerebrovascular, conduit- and thermoregulatory adaptations compared to a period of moderate-intensity exercise training over 8-weeks

EXERCISE TRAINING REDUCES THE FREQUENCY OF MENOPAUSAL HOT FLUSHES BY IMPROVING THERMOREGULATORY CONTROL

Objectives: Post-menopausal hot flushes occur due to a reduction in oestrogen production causing thermoregulatory and vascular dysfunction. Exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. We aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes. Methods: Twenty one symptomatic females completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. Sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (MCAv) was measured during passive heating. Females performed 16-weeks of supervised exercise training or control, and measurements were repeated. Results: There was a greater improvement in cardiorespiratory fitness (4.45 ml•kg-1•min-1 (95% CI: 1.87, 8.16; P=0.04) and reduced hot flush frequency [48 hot flushes•week (39, 56) P<0.001] following exercise compared to control. Exercise reduced basal core temperature [0.14°C (0.01, 0.27) P=0.03] and increased basal MCAv [2.8 cm/s (1.0 to 5.2) P=0.04] compared to control. Sweat rate and skin blood flow thresholds occurred ~0.19 and 0.17°C earlier, alongside improved sweating sensitivity with exercise. MCAv decreased during heating [P<0.005], but was maintained 4.5 cm/s (3.6, 5.5 P<0.005) higher during heating following exercise compared to control [0.6 cm/s (-0.4, 1.4)]. Conclusions: Exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. Improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations