DYNamic assessment of multi-organ level dysfunction in patients recovering from COVID-19: DYNAMO COVID-19.

We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5-7 months post-discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole-body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual-energy X-ray absorptiometry, short physical performance battery (SPPB), intra-muscular electromyography, quadriceps strength and fatigability, and daily step-count. There was a greater insulin response (incremental area under the curve, median (inter-quartile range)) during the OGTT in patients [18,289 (12,497-27,448) mIU/min/L] versus controls [8655 (7948-11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post-prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole-body/regional adiposity, but step-count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force-loss, motor unit properties and post-exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross-sectional study, individuals without known previous morbidity who survived severe COVID-19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery.

A comparative, randomised MRI study of the physiological and appetitive responses to gelling (alginate) and non-gelling nasogastric tube feeds in healthy men.

Inclusion in nasogastric tube feeds (NGTF) of acid-sensitive, seaweed-derived alginate, expected to form a reversible gel in the stomach, may create a more normal intragastric state and modified gastrointestinal responses. This may ameliorate NGTF-associated risk of diarrhoea, upper gastrointestinal symptoms and appetite suppression. In a randomised, crossover, comparison study, undertaken in twelve healthy males, an alginate-containing feed (F + ALG) or one that was alginate-free (F-ALG) (300 ml) was given over 1 h with a 7-14-d washout period between treatments. Baseline and for 4-h post-feed initiation, MRI measurements were made to establish small bowel water content (SBWC), gastric contents volume (GCV) and appearance, and superior mesenteric artery blood flux. Blood glucose and gut peptides were measured. Subjective appetite and upper gastrointestinal symptoms scores were obtained. Ad libitum pasta consumption 3-h post-feeding was measured. F + ALG exhibited a gastric appearance consistent with gelling surrounded by a freely mobile water halo. Significant main effects of feed were seen for SBWC (P = 0·03) and peptide YY (PYY) (P = 0·004) which were attributed to generally higher values for SBWC with F + ALG (max difference between adjusted means 72 ml at 210 min) and generally lower values for PYY with F + ALG. GCV showed a faster reduction with F + ALG, less between-participant variation and a feed-by-time interaction (P = 0·04). Feed-by-time interactions were also seen with glucagon-like-peptide 1 (GLP-1) (P = 0·02) and glucose-dependent insulinotropic polypeptide (GIP) (P = 0·002), both showing a blunted response with F + ALG. Apparent intragastric gelling with F + ALG and subsequent differences in gastrointestinal and endocrine responses have been demonstrated between an alginate-containing and alginate-free feed.

Immobilisation induces sizeable and sustained reductions in forearm glucose uptake in just 24 h but does not change lipid uptake in healthy men.

KEY POINTS: The trajectory, magnitude and localisation of metabolic perturbations caused by immobilisation (IMM) are unresolved. Forearm glucose uptake (FGU) in response to glucose feeding was determined in healthy men before and during 72 h of forearm IMM, and the same measurements were made in the non-IMM contralateral limb at baseline and 72 h. In a similar study design, FGU and forearm lipid uptake were determined after a high fat mixed-meal (HFMM) in IMM and non-IMM limbs. FGU was reduced by 38%, 57% and 46% following 24, 48 and 72 h IMM, respectively, but was unchanged in the non-IMM limb. A similar FGU response to IMM was observed after a HFMM, and forearm lipid uptake was unchanged. A sizeable reduction in FGU occurs in just 24 h of IMM, which is sustained thereafter and specific to the IMM limb, making unloading per se the likely rapid driver of dysregulation. ABSTRACT: The trajectory and magnitude of metabolic perturbations caused by muscle disuse are unknown yet central to understanding the mechanistic basis of immobilisation-associated metabolic dysregulation. To address this gap, forearm glucose uptake (FGU) was determined in 10 healthy men (age 24.9 ± 0.6 years, weight 71.9 ± 2.6 kg, BMI 22.6 ± 0.6 kg/m2 ) during a 180 min oral glucose challenge before (0) and after 24, 48 and 72 h of arm immobilisation, and before and after 72 h in the contralateral non-immobilised arm (Study A). FGU was decreased from baseline at 24 h (38%, P = 0.04), 48 h (57%, P = 0.01) and 72 h (46%, P = 0.06) of immobilisation, and was also 63% less than the non-immobilised limb at 72 h (P = 0.002). In a second study, FGU and forearm lipid uptake were determined in nine healthy men (age 22.4 ± 1.3 years, weight 71.4 ± 2.8 kg, BMI 22.6 ± 0.8 kg/m2 ) during a 420 min mixed-meal challenge before (0) and after 24 and 48 h of arm immobilisation and before and after 72 h in the contralateral non-immobilised arm (Study B). FGU responses were similar to Study A, and forearm lipid uptake was unchanged from pre-immobilisation in both arms over the study. A sizeable decrement in FGU in response to glucose feeding occurred within 24 h of immobilisation that was sustained and specific to the immobilised limb. Increasing lipid availability had no additional impact on the rate or magnitude of these responses or on lipid uptake. These findings highlight a lack of muscle contraction per se as a fast-acting physiological insult to FGU.

An investigation into the spiritual needs of neuro-oncology patients from a nurse perspective.

BACKGROUND: Spiritual needs of cancer patients should be assessed and discussed by healthcare professionals. Neurosurgical nurses need to be able to assess and support neuro-oncology patients with their spiritual needs from diagnosis and throughout their hospital stay. METHODS: Data were collected through questionnaires using a Critical Incident Technique (CIT) from neurosurgical nurses, findings were analysed using thematic analysis. RESULTS: Nurses reported some awareness of their patients' spiritual needs during their stay on neurosurgical units although some used expressions approximating what could be described as spiritual needs. Patients' spiritual needs were identified as: need to talk about spiritual concerns, showing sensitivity to patients' emotions, responding to religious needs; and relatives' spiritual needs included: supporting them with end of life decisions, supporting them when feeling being lost and unbalanced, encouraging exploration of meaning of life, and providing space, time and privacy to talk. Participants appeared largely to be in tune with their patients' spiritual needs and reported that they recognised effective strategies to meet their patients' and relatives' spiritual needs. However, the findings also suggest that they don't always feel prepared to offer spiritual support for neuro-oncology patients. CONCLUSIONS: There is a need for healthcare professionals to provide spiritual care for neuro-oncology patients and their relatives. Although strategies were identified that nurses can use to support patients with spiritual needs further research is required to explore how effective nurses are at delivering spiritual care and if nurses are the most appropriate professionals to support neuro-oncology patients with spiritual care.

Antecubital Vein Cannula Position Impacts Assessment of Forearm Glucose Uptake During an Oral Glucose Challenge in Healthy Volunteers.

INTRODUCTION: Skeletal muscle is a major site for whole-body glucose disposal, and determination of skeletal muscle glucose uptake is an important metabolic measurement, particularly in research focussed on interventions that impact muscle insulin sensitivity. Calculating arterial-venous difference in blood glucose can be used as an indirect measure for assessing glucose uptake. However, the possibility of multiple tissues contributing to the composition of venous blood, and the differential in glucose uptake kinetics between tissue types, suggests that sampling from different vein sites could influence the estimation of glucose uptake. This study aimed to determine the impact of venous cannula position on calculated forearm glucose uptake following an oral glucose challenge in resting and post-exercise states. MATERIALS AND METHODS: In 9 young, lean, males, the impact of sampling blood from two antecubital vein positions; the perforating vein ('perforating' visit) and, at the bifurcation of superficial and perforating veins ('bifurcation' visit), was assessed. Brachial artery blood flow and arterialised-venous and venous blood glucose concentrations were measured in 3 physiological states; resting-fasted, resting-fed, and fed following intermittent forearm muscle contraction (fed-exercise). RESULTS: Following glucose ingestion, forearm glucose uptake area under the curve was greater for the 'perforating' than for the 'bifurcation' visit in the resting-fed (5.92±1.56 vs. 3.69±1.35 mmol/60 min, P<0.01) and fed-exercise (17.38±7.73 vs. 11.40±7.31 mmol/75 min, P<0.05) states. DISCUSSION: Antecubital vein cannula position impacts calculated postprandial forearm glucose uptake. These findings have implications for longitudinal intervention studies where serial determination of forearm glucose uptake is required.

Skeletal muscle anabolic and insulin sensitivity responses to a mixed meal in adult patients with active Crohn's disease.

BACKGROUND AND AIMS: We have previously shown reduced protein balance in response to nutrition in paediatric Crohn's disease (CD) in remission, associated with reduced lean mass (sarcopenia) and reduced protein intake in males. We aim to compare skeletal muscle metabolic response to feeding in adult active CD and healthy volunteers. METHODS: Eight CD participants with active disease (41.3 ± 4.5 yrs; BMI 26.9 ± 1.5 kg/m2) and eight matched healthy volunteers (Con) (41.2 ± 4.3 yrs; BMI 25.1 ± 1.1 kg/m2) were recruited. Participants had a dual energy X-ray absorptiometry scan, handgrip dynamometer test, wore a pedometer and completed a food diary. Arterialized hand and venous forearm blood samples were collected concurrently and brachial artery blood flow measured at baseline and every 20mins for 2hrs after the ingestion of a standardized mixed liquid meal. Net balance of branched chain amino acids (BCAA), glucose and free fatty acids across the forearm were derived. RESULTS: No differences in muscle BCAA, glucose or FFA net balance were found between CD and Con. Neither were differences in muscle mass and function, physical activity or diet found. CD did not differ from Con in whole body insulin and lipid responses, or in energy expenditure and fuel oxidation. CONCLUSIONS: Skeletal muscle mass, function, dietary protein intake and response to a test meal in an adult CD cohort with active disease is similar to that seen in healthy volunteers. Combining these results with our previous findings in paediatric patients suggests that age of onset and/or disease burden over time, as well as daily protein intake, may be significant in the development of sarcopenia in CD. Longitudinal studies investigating these factors are required.

The spiritual needs of neuro-oncology patients from patients' perspective.

AIMS: This study aimed to identify the spiritual needs of neuro-oncology patients from a patient perspective and how nurses currently support patients with spiritual needs. BACKGROUND: Spiritual needs of cancer patients should be assessed and discussed by healthcare professionals from diagnosis. Nurses should assess and support neuro-oncology patients with their spiritual needs during their hospital stay. DESIGN: Qualitative research. METHODS: Data were collected through a Critical Incident Technique questionnaire from neuro-oncology patients and were subjected to thematic content analysis. RESULTS: Some patients with brain tumours do report spiritual needs during their hospital stay and some of these needs are not met by nurses. CONCLUSIONS: There is clearly a need for healthcare professionals to provide spiritual care for neuro-oncology patients and their relatives. Further research is required to explore how effective nurses are at delivering spiritual care and if nurses are the most appropriate professionals to support neuro-oncology patients with spiritual care. RELEVANCE TO CLINICAL PRACTICE: The study illuminates that some neuro-oncology patients' have spiritual needs that could be met by nurses. Spiritual needs include supportive family relationships, emotional support, loneliness, religious needs, need to talk, reassurance, anxiety, solitude, denial, plans for the future, thoughts about meaning of life, end of life decisions and discussion of beliefs. The implications of the findings of this study are that nurses need to be aware and respond to these spiritual needs.

Two weeks of early time-restricted feeding (eTRF) improves skeletal muscle insulin and anabolic sensitivity in healthy men.

BACKGROUND: Altering the temporal distribution of energy intake (EI) and introducing periods of intermittent fasting (IF) exert important metabolic effects. Restricting EI to earlier in the day [early time-restricted feeding (eTRF)] is a novel type of IF. OBJECTIVES: We assessed the chronic effects of eTRF compared with an energy-matched control on whole-body and skeletal muscle insulin and anabolic sensitivity. METHODS: Sixteen healthy males (aged 23 ± 1 y; BMI 24.0 ± 0.6 kg·m-2) were assigned to 2 groups that underwent either 2 wk of eTRF (n = 8) or control/caloric restriction (CON:CR; n = 8) diet. The eTRF diet was consumed ad libitum and the intervention was conducted before the CON:CR, in which the diet was provided to match the reduction in EI and body weight observed in eTRF. During eTRF, daily EI was restricted to between 08:00 and 16:00, which prolonged the overnight fast by ∼5 h. The metabolic responses to a carbohydrate/protein drink were assessed pre- and post-interventions following a 12-h overnight fast. RESULTS: When compared with CON:CR, eTRF improved whole-body insulin sensitivity [between-group difference (95% CI): 1.89 (0.18, 3.60); P = 0.03; η2p = 0.29] and skeletal muscle uptake of glucose [between-group difference (95% CI): 4266 (261, 8270) µmol·min-1·kg-1·180 min; P = 0.04; η2p = 0.31] and branched-chain amino acids (BCAAs) [between-group difference (95% CI): 266 (77, 455) nmol·min-1·kg-1·180 min; P = 0.01; η2p = 0.44]. eTRF caused a reduction in EI (∼400 kcal·d-1) and weight loss (-1.04 ± 0.25 kg; P = 0.01) that was matched in CON:CR (-1.24 ± 0.35 kg; P = 0.01). CONCLUSIONS: Under free-living conditions, eTRF improves whole-body insulin sensitivity and increases skeletal muscle glucose and BCAA uptake. The metabolic benefits of eTRF are independent of its effects on weight loss and represent chronic adaptations rather than the effect of the last bout of overnight fast. This trial was registered at clinicaltrials.gov as NCT03969745.

Reduced skeletal muscle protein balance in paediatric Crohn's disease.

BACKGROUND & AIMS: An inability to respond to nutrition could be implicated in low muscle mass in Crohn's disease. We aim to determine skeletal muscle metabolic response to feeding in Crohn's disease and healthy volunteers. METHODS: Twenty asymptomatic Crohn's disease participants (15.6 ± 0.5 yrs; BMI 20.6 ± 0.9 kg/m2); 9 with active disease (faecal calprotectin, 808 ± 225 ug/g and C-reactive protein, 2.2 ± 1.2 mg/dl), 11 in deep remission (faecal calprotectin, 61 ± 12 ug/g and C-reactive protein, 0.3 ± 0.2 mg/dl) and 9 matched healthy volunteers (16.0 ± 0.6 yrs; BMI 20.7 ± 0.6 kg/m2) were recruited. Participants had a dual energy X-ray absorptiometry scan, handgrip dynamometer test, wore a pedometer and completed a food diary. Arterialised hand and venous forearm blood samples were collected concurrently and brachial artery blood flow measured at baseline and every 20 min for 2 hrs after the ingestion of a standardised liquid meal. Net balance of branched chain amino acids (BCAA) and glucose were derived. RESULTS: Controls had a positive mean BCAA balance. CD participants had an initial anabolic response to the meal, with increasing BCAA balance between t = 0 & t = 20, but returned to negative by t = 60. This was associated with reduced FFM z-scores in CD but not with insulin resistance or disease activity. Exploratory analyses suggest that negative postprandial BCAA response seen in CD is predominant in males (p = 0.049), with associated lower appendicular muscle mass (p = 0.034), higher muscle fatigue (p = 0.014) and reduced protein intake (p = 0.026). CONCLUSIONS: The inability to sustain a positive protein balance postprandially could provide an explanation for the reduced muscle mass seen in CD. Further mechanistic studies will be needed to confirm these findings.

Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men.

BACKGROUND: Increasing skeletal muscle carnitine content represents an appealing intervention in conditions of perturbed lipid metabolism such as obesity and type 2 diabetes but requires chronic L-carnitine feeding on a daily basis in a high-carbohydrate beverage. OBJECTIVE: We investigated whether whey protein ingestion could reduce the carbohydrate load required to stimulate insulin-mediated muscle carnitine accretion. DESIGN: Seven healthy men [mean ± SD age: 24 ± 5 y; body mass index (in kg/m(2)): 23 ± 3] ingested 80 g carbohydrate, 40 g carbohydrate + 40 g protein, or control (flavored water) beverages 60 min after the ingestion of 4.5 g L-carnitine tartrate (3 g L-carnitine; 0.1% (2)[H]3-L-carnitine). Serum insulin concentration, net forearm carnitine balance (NCB; arterialized-venous and venous plasma carnitine difference × brachial artery flow), and carnitine disappearance (Rd) and appearance (Ra) rates were determined at 20-min intervals for 180 min. RESULTS: Serum insulin and plasma flow areas under the curve (AUCs) were similarly elevated by carbohydrate [4.5 ± 0.8 U/L · min (P < 0.01) and 0.5 ± 0.6 L (P < 0.05), respectively] and carbohydrate+protein [3.8 ± 0.6 U/L · min (P < 0.01) and 0.4 ± 0.6 L (P = 0.05), respectively] consumption, respectively, compared with the control visit (0.04 ± 0.1 U/L · min and -0.5 ± 0.2 L). Plasma carnitine AUC was greater after carbohydrate+protein consumption (3.5 ± 0.5 mmol/L · min) than after control and carbohydrate visits [2.1 ± 0.2 mmol/L · min (P < 0.05) and 1.9 ± 0.3 mmol/L · min (P < 0.01), respectively]. NCB AUC with carbohydrate (4.1 ± 3.1 µmol) was greater than during control and carbohydrate-protein visits (-8.6 ± 3.0 and -14.6 ± 6.4 µmol, respectively; P < 0.05), as was Rd AUC after carbohydrate (35.7 ± 25.2 µmol) compared with control and carbohydrate consumption [19.7 ± 15.5 µmol (P = 0.07) and 14.8 ± 9.6 µmol (P < 0.05), respectively]. CONCLUSIONS: The insulin-mediated increase in forearm carnitine balance with carbohydrate consumption was acutely blunted by a carbohydrate+protein beverage, which suggests that carbohydrate+protein could inhibit chronic muscle carnitine accumulation.