Measuring nutrition-related outcomes in a cohort of multi-trauma patients following intensive care unit discharge.

BACKGROUND: Functional recovery is an important outcome for those who survive critical illness. The present study aimed to assess nutrition provision and nutrition-related outcomes in a multi-trauma cohort following intensive care unit (ICU) discharge. METHODS: The present study investigated a prospective cohort of patients discharged from an ICU, who had been admitted because of major trauma and required mechanical ventilation for at least 48 h. Nutrition-related outcomes, including body weight, quadriceps muscle layer thickness (QMLT), handgrip strength and subjective global assessment, were recorded on ICU discharge, days 5-7 post-ICU discharge and then weekly until hospital discharge. Nutrition intake was recorded for 5 days post-ICU discharge. Unless otherwise stated, data are presented as the mean (SD). RESULTS: Twenty-eight patients [75% males, 55 (22.5) years] were included. Intake met 64% (28%) of estimated energy and 72% (32%) of protein requirements over the 5 days post-ICU discharge, which was similar to over the ICU admission. From ICU admission to hospital discharge, the mean reduction in weight was 4.2 kg (95% confidence interval = 2.2-6.3, P < 0.001) and after ICU discharge, the mean reduction in weight and QMLT was 2.6 kg (95% confidence interval = 1.0-4.2, P = 0.004) and 0.23 cm (95% confidence interval = 0.06-0.4, P = 0.01), respectively. CONCLUSIONS: Patients received less energy and protein than estimated requirements after ICU discharge. Weight loss and reduction in QMLT also occurred during this period.

Associations between nutritional energy delivery, bioimpedance spectroscopy and functional outcomes in survivors of critical illness.

BACKGROUND: Patients who survive critical illness frequently develop muscle weakness that can impact on quality of life; nutrition is potentially a modifiable risk factor. The present study aimed to explore the associations between cumulative energy deficits (using indirect calorimetry and estimated requirements), nutritional and functional outcomes. METHODS: A prospective single-centre observational study of 60 intensive care unit (ICU) patients, who were mechanically ventilated for at least 48 h, was conducted. Cumulative energy deficit was determined from artificial nutrition delivery compared to targets. Measurements included: (i) at recruitment and ICU discharge, weight, fat-free mass (bioimpedance spectroscopy) and malnutrition (Subjective Global Assessment score B/C); (ii) at awakening and ICU discharge, physical function (Physical Function in Intensive Care Test-scored) and muscle strength (Medical Research Council sum-score (MRC-SS). ICU-acquired weakness was defined as a MRC-SS score of less than 48/60. RESULTS: The median (interquartile range) cumulative energy deficit compared to the estimated targets up to ICU day 12 was 3648 (2514-5650) kcal. Adjusting for body mass index, age and severity of illness, cumulative energy deficit (per 1000 kcal) was independently associated with greater odds of ICU-acquired weakness [odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.4-3.3, P = 0.001] and malnutrition (OR = 1.9, 95% CI = 1.1-3.2, P = 0.02). In similar multivariable linear models, cumulative energy deficit was associated with reductions in fat-free mass (-1.3 kg; 95% CI = -2.4 to -0.2, P = 0.02) and physical function scores (-0.6 points; 95% CI = -0.9 to -0.3, P = 0.001). CONCLUSIONS: Cumulative energy deficit from artificial nutrition support was associated with reduced functional outcomes and greater loss of fat-free mass in ventilated ICU patients.

Occult upper gastrointestinal mucosal abnormalities in critically ill patients.

BACKGROUND: The objectives of this study were to estimate the frequency of occult upper gastrointestinal abnormalities, presence of gastric acid as a contributing factor, and associations with clinical outcomes. METHODS: Data were extracted for study participants at a single centre who had an endoscopy performed purely for research purposes and in whom treating physicians were not suspecting gastrointestinal bleeding. Endoscopic data were independently adjudicated by two gastroenterologists who rated the likelihood that observed pathological abnormalities were related to gastric acid secretion using a 3-point ordinal scale (unlikely, possible or probable). RESULTS: Endoscopy reports were extracted for 74 patients [age 52 (37, 65) years] undergoing endoscopy on day 5 [3, 9] of ICU admission. Abnormalities were found in 25 (34%) subjects: gastritis/erosions in 10 (14%), nasogastric tube trauma in 8 (11%), oesophagitis in 4 (5%) and non-bleeding duodenal ulceration in 3 (4%). The contribution of acid secretion to observed pathology was rated 'probable' in six subjects (rater #1) and five subjects (rater #2). Prior to endoscopy, 39 (53%) patients were receiving acid-suppressive therapy. The use of acid-suppressive therapy was not associated with the presence of an endoscopic abnormality (present 15/25 (60%) vs. absent 24/49 (49%); P = 0.46). Haemoglobin concentrations, packed red cells transfused and mortality were not associated with mucosal abnormalities (P = 0.83, P > 0.9 and P > 0.9 respectively). CONCLUSIONS: Occult mucosal abnormalities were observed in one-third of subjects. The presence of mucosal abnormalities appeared to be independent of prior acid-suppressive therapy and was not associated with reduced haemoglobin concentrations, increased transfusion requirements, or mortality.

Weekend days are not required to accurately measure oral intake in hospitalised patients.

BACKGROUND: Nutrition studies in patients admitted to hospital frequently disregard oral intake because measurement is time-intensive and logistically challenging. In free-living populations, weighed food records (WFR) are the gold-standard and are conducted on weekend and weekdays to capture variations in intake, although this may not translate during hospitalisation. The present study aimed to determine whether oral intake differs between weekends and weekdays in hospitalised patients. METHODS: For adult patients initially admitted to the intensive therapy unit with a moderate-severe head injury over a 12-month period, WFR were conducted each week on Tuesday, Thursday and Saturday throughout hospitalisation. Meal components were weighed before and after consumption, and energy and protein intakes were calculated using specialised software. Data are reported as the mean (SD). Differences were assessed using paired t-tests and agreement using Bland-Altman plots. RESULTS: Thirty-two patients had WFR collected on 220 days, 68% (n = 149) on weekdays and 32% (n = 71) on weekends. Overall, daily intakes were 5.72 (3.67) MJ [1367 (877) kcal] and 62 (40) g protein. There were no differences in intake across all days (P = 0.937 energy, P = 0.797 protein), nor between weekdays and weekends, in weeks 1-3 of oral intake (all P > 0.1). Limits of agreement between mean intakes across days were wide for energy [range -11.20 to 9.55 MJ (-2680 to 2283 kcal)] and protein (range -125 to 110 g). CONCLUSIONS: Grouped energy and protein intakes from WFR in hospitalised patients are similar on weekdays and weekends, although large intra-patient variations occur. Future quantification of oral intake during hospitalisation should include as many days as feasible, although not necessarily weekend days, to reflect true intake.

Peri-operative nutrition.

Patients are frequently malnourished or are at risk of malnutrition before surgery. Peri-operative nutritional support can improve their outcomes. This review focuses on new developments in peri-operative nutrition, including: patient preparation and pre-operative fasting; the role of nutritional supplementation; the optimal route and timing of nutrient delivery; and the nutritional management of specific groups including critically ill, obese and elderly patients.

Definition, prevalence, and outcome of feeding intolerance in intensive care: a systematic review and meta-analysis.

Clinicians and researchers frequently use the phrase 'feeding intolerance' (FI) as a descriptive term in enterally fed critically ill patients. We aimed to: (1) determine what is the most accepted definition of FI; (2) estimate the prevalence of FI; and (3) evaluate whether FI is associated with important outcomes. Systematic searches of peer-reviewed publications using PubMed, MEDLINE, and Web of Science were performed with studies reporting FI extracted. We identified 72 studies defining FI. In 33 studies, the definition was based on large gastric residual volumes (GRVs) together with other gastrointestinal symptoms, while 30 studies relied solely on large GRVs, six studies used inadequate delivery of enteral nutrition (EN) as a threshold, and three studies gastrointestinal symptoms without reference to GRV. The median volume used to define a 'large' GRV was 250 ml (ranges from 75 to 500 ml). The pooled proportion (n = 31 studies) of FI was 38.3% (95% CI 30.7-46.2). Five studies reported outcomes, all of them observed adverse outcome in FI patients. In three studies, respectively, FI was associated with increased mortality and ICU length-of-stay. In summary, FI is inconsistently defined but appears to occur frequently. There are preliminary data indicating that FI is associated with adverse outcomes. A standard definition of FI is required to determine the accuracy of these preliminary data.

Endogenous amylin and glucagon-like peptide-1 concentrations are not associated with gastric emptying in critical illness.

BACKGROUND: In health, the hormones amylin and glucagon-like peptide-1 (GLP-1) slow gastric emptying (GE) and modulate glycaemia. The aims of this study were to determine amylin and GLP-1 concentrations in the critically ill and their relationship with GE, glucose absorption and glycaemia. METHODS: In fasted critically ill and healthy subjects (n = 26 and 23 respectively), liquid nutrient, containing 100 mg (13) C-sodium octanoate and 3 g 3-O-methlyglucose (3-OMG), was administered via a nasogastric tube. Amylin, GLP-1, glucose and 3-OMG concentrations were measured in blood samples taken during fasting, and 30 min and 60 min after the 'meal'. Breath samples were taken to determine gastric emptying coefficient (GEC). Intolerance to intragastric feeding was defined as a gastric residual volume of ≥ 250 ml and/or vomiting within the 24 h prior to the study. RESULTS: Although GE was slower (GEC: critically ill 2.8 ± 0.9 vs. health, 3.4 ± 0.2; P = 0.002), fasting blood glucose was higher (7.0 ± 1.9 vs. 5.7 ± 0.2 mmol/l; P = 0.005) and overall glucose absorption was reduced in critically ill patients (3-OMG: 9.4 ± 8.0 vs. 17.7 ± 4.9 mmol/l.60 min; P < 0.001), there were no differences in fasting or postprandial amylin concentrations. Furthermore, although fasting [1.7 (0.4-7.2) vs. 0.7 (0.3-32.0) pmol/l; P = 0.04] and postprandial [3.0 (0.4-8.5) vs. 0.8 (0.4-34.3) pmol/l; P = 0.02] GLP-1 concentrations were increased in the critically ill and were greater in feed intolerant when compared with those tolerating feed [3.7 (0.4-7.2) vs. 1.2 (0.7-4.6) pmol/l; P = 0.02], there were no relationships between GE and fasting amylin or GLP-1 concentrations. CONCLUSION: In the critically ill, fasting GLP-1, but not amylin, concentrations are elevated and associated with feed intolerance. Neither amylin nor GLP-1 appears to substantially influence the rate of GE.

Dysglycaemia in the critically ill - significance and management.

Hyperglycaemia frequently occurs in the critically ill, in patients with diabetes, as well as those who were previously glucose-tolerant. The terminology 'stress hyperglycaemia' reflects the pathogenesis of the latter group, which may comprise up to 40% of critically ill patients. For comparable glucose concentrations during acute illness outcomes in stress hyperglycaemia appear to be worse than those in patients with type 2 diabetes. While several studies have evaluated the optimum glycaemic range in the critically ill, their interpretation in relation to clinical recommendations is somewhat limited, at least in part because patients with stress hyperglycaemia and known diabetes were grouped together, and the optimum glycaemic range was regarded as static, rather than dynamic, phenomenon. In addition to hyperglycaemia, there is increasing evidence that hypoglycaemia and glycaemic variability influence outcomes in the critically ill adversely. These three categories of disordered glucose metabolism can be referred to as dysglycaemia. While stress hyperglycaemia is most frequently managed by administration of short-acting insulin, guided by simple algorithms, this does not treat all dysglycaemic categories; rather the use of insulin increases the risk of hypoglycaemia and may exacerbate variability. The pathogenesis of stress hyperglycaemia is complex, but hyperglucagonaemia, relative insulin deficiency and insulin resistance appear to be important. Accordingly, novel agents that have a pathophysiological rationale and treat hyperglycaemia, but do not cause hypoglycaemia and limit glycaemic variability, are appealing. The potential use of glucagon-like peptide-1 (or its agonists) and dipeptyl-peptidase-4 inhibitors is reviewed.

Mitogen-activated protein kinase (MAPK) signalling corresponds with distinct behavioural profiles in a rat model of maternal immune activation.

Dysfunction within the mitogen-activated protein kinase (MAPK) cascade has been recognised as a pathological feature of schizophrenia, however the possible mechanistic connection to the disease phenotype remains unexplored. Using the maternal immune activation (MIA) rat model of schizophrenia, the present study investigated the involvement of prefrontal cortex (PFC) MAPK in sensorimotor gating and adaptive learning deficits via western blot, pre-pulse inhibition (PPI) testing, and a contingency degradation operant task, respectively. Principle findings identified a negative relationship between basal MAPK expression and PPI exclusively in MIA rats, suggesting a modulatory role for MAPK in sensorimotor gating pathology. In addition, the correlation between MAPK and adaptive learning capacity observed in control rats was absent for rats exposed to MIA. Findings are considered with respect to the glutamatergic NMDA hypofunction theory of schizophrenia, as well as the critical role of PFC in contingency learning.

Catalytic atroposelective dynamic kinetic resolutions and kinetic resolutions towards 3-arylquinolines via SNAr.

Herein we report the catalytic atroposelective syntheses of pharmaceutically relevant 3-arylquinolines via the nucleophilic aromatic substitution (SNAr) of thiophenols into 3-aryl-2-fluoroquinolines mediated by catalytic amounts of Cinchona alkaloid-derived ureas. These reactions displayed a spectrum of dynamic kinetic resolution (DKR) and kinetic resolution (KR) characters depending upon the stereochemical stability of the starting material. Low barrier substrates proceeded via DKR while higher barrier substrates proceeded via KR. On the other hand, substrates with intermediate stabilities displayed hallmarks of both DKR and KR. Finally, we also show that we can functionalize the atropisomerically enriched quinolines into pharmaceutically privileged scaffolds with minimal observed racemization.

Laboratory experiments on planetary and stellar convection performed on spacelab 3.

Experiments on thermal convection in a rotating, differentially heated hemispherical shell with a radial buoyancy force were conducted in an orbiting microgravity laboratory. A variety of convective structures, or planforms, were observed, depending on the magnitude of the rotation and the nature of the imposed heating distribution. The results are compared with numerical simulations that can be conducted at the more modest heating rates, and suggest possible regimes of motion in rotating planets and stars.

Intergenerational transmission of adverse childhood experiences via maternal depression and anxiety and moderation by child sex.

Adverse childhood experiences (ACEs) of parents are associated with a variety of negative health outcomes in offspring. Little is known about the mechanisms by which ACEs are transmitted to the next generation. Given that maternal depression and anxiety are related to ACEs and negatively affect children's behaviour, these exposures may be pathways between maternal ACEs and child psychopathology. Child sex may modify these associations. Our objectives were to determine: (1) the association between ACEs and children's behaviour, (2) whether maternal symptoms of prenatal and postnatal depression and anxiety mediate the relationship between maternal ACEs and children's behaviour, and (3) whether these relationships are moderated by child sex. Pearson correlations and latent path analyses were undertaken using data from 907 children and their mothers enrolled the Alberta Pregnancy Outcomes and Nutrition study. Overall, maternal ACEs were associated with symptoms of anxiety and depression during the perinatal period, and externalizing problems in children. Furthermore, we observed indirect associations between maternal ACEs and children's internalizing and externalizing problems via maternal anxiety and depression. Sex differences were observed, with boys demonstrating greater vulnerability to the indirect effects of maternal ACEs via both anxiety and depression. Findings suggest that maternal mental health may be a mechanism by which maternal early life adversity is transmitted to children, especially boys. Further research is needed to determine if targeted interventions with women who have both high ACEs and mental health problems can prevent or ameliorate the effects of ACEs on children's behavioural psychopathology.

The rapid and accurate categorisation of critically ill patients (RACE) to identify outcomes of interest for longitudinal studies: a feasibility study.

The capacity to measure the impact of an intervention on long-term functional outcomes might be improved if research methodology reflected our clinical approach, which is to individualise goals of care to what is achievable for each patient. The objective of this multicentre inception cohort study was to evaluate the feasibility of rapidly and accurately categorising patients, who were eligible for simulated enrolment into a clinical trial, into unique categories based on premorbid function. Once a patient met eligibility criteria a rapid 'baseline assessment' was conducted to categorise patients into one of eight specified groups. A subsequent 'gold standard' assessment was made by an independent blinded assessor once patients had recovered sufficiently to allow such an assessment to occur. Accuracy was predefined as agreement in >80% of assessments. One hundred and twenty-two patients received a baseline assessment and 104 (85%) were categorised to a unique category. One hundred and six patients survived to have a gold standard assessment performed, with 100 (94%) assigned to a unique category. Ninety-two patients had both a baseline and gold standard assessment, and these agreed in 65 (71%) patients. It was not feasible to rapidly and accurately categorise patients according to premorbid function.

Enhanced Protein-Energy Provision via the Enteral Route Feeding (PEPuP) protocol in critically ill surgical patients: a multicentre prospective evaluation.

Suboptimal levels of feeding in critically ill patients are associated with poor clinical outcomes. The Enhanced Protein-Energy Provision via the Enteral Route Feeding (PEPuP) protocol was developed to improve nutritional delivery in the critically ill and has been studied in several hospitals. However, the experience with this protocol in surgical patients is limited to date. The objective of this analysis was to describe the experience with this protocol in surgical patients. We analysed observational patient data obtained from the 2013 International Nutrition Survey. We compared nutritional practices and outcomes of patients admitted for surgical and medical reasons to ICUs in sites that implemented the PEPuP protocol. We used surgical ICU patients in non-PEPuP sites as a concurrent control group. In sites that implemented the PEPuP protocol, surgical patients received a smaller proportion of prescribed calories (43% versus 61%, P=0.004) and protein (38% versus 57%, P=0.002) compared to medical patients. When compared to the cohort of surgical patients from control sites, the surgical patients from PEPuP sites received similar amounts of calories and protein. Although surgical PEPuP patients were more likely to receive trophic and volume-based feeds compared to surgical patients in control sites, other aspects of the PEPuP protocol were not adequately implemented. We conclude that nutritional delivery to surgical patients remains inadequate and the PEPuP protocol seems ineffective in improving nutritional intake in this population. Further research to determine methods of optimising PEPuP protocol implementation and adherence in surgery patients is needed.

The effect of augmenting early nutritional energy delivery on quality of life and employment status one year after ICU admission.

Augmenting energy delivery during the acute phase of critical illness may reduce mortality and improve functional outcomes. The objective of this sub-study was to evaluate the effect of early augmented enteral nutrition (EN) during critical illness, on outcomes one year later. We performed prospective longitudinal evaluation of study participants, initially enrolled in The Augmented versus Routine approach to Giving Energy Trial (TARGET), a feasibility study that randomised critically ill patients to 1.5 kcal/ml (augmented) or 1.0 kcal/ml (routine) EN administered at the same rate for up to ten days, who were alive at one year. One year after randomisation Short Form-36 version 2 (SF-36v2) and EuroQol-5D-5L quality of life surveys, and employment status were assessed via telephone survey. At one year there were 71 survivors (1.5 kcal/ml 38 versus 1.0 kcal/ml 33; P=0.55). Thirty-nine (55%) patients consented to this follow-up study and completed the surveys (n = 23 and 16, respectively). The SF-36v2 physical and mental component summary scores were below normal population means but were similar in 1.5 kcal/ml and 1.0 kcal/ml groups (P=0.90 and P=0.71). EuroQol-5D-5L data were also comparable between groups (P=0.70). However, at one-year follow-up, more patients who received 1.5 kcal/ml were employed (7 versus 2; P=0.022). The delivery of 1.5 kcal/ml for a maximum of ten days did not affect self-rated quality of life one year later.

Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization.

Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM10-induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.

The incidence of ocular candidiasis and evaluation of routine opthalmic examination in critically ill patients with candidaemia.

Despite a paucity of data regarding both the incidence of ocular candidiasis and the utility of ophthalmic examination in critically ill patients, routine ophthalmic examination is recommended for critically ill patients with candidaemia. The objectives were to estimate the incidence of ocular candidiasis and evaluate whether ophthalmic examination influenced subsequent management of these patients. We conducted a ten-year retrospective observational study. Data were extracted for all ICU patients who were blood culture positive for fungal infection. Risk factors for candidaemia and eye involvement were quantified and details regarding ophthalmic examination were reviewed. Candida species were cultured in 93 patients. Risk factors for ocular candidiasis were present in 57% of patients. Forty-one percent of patients died prior to ophthalmology examination and 2% of patients were discharged before candidaemia was identified. During examination, signs of ocular candidiasis were only present in one (2.9%) patient, who had a risk factor for ocular candidiasis. Based on these findings, the duration of antifungal treatment for this patient was increased. Ocular candidiasis occurs rarely in critically ill patients with candidaemia, but because treatment regimens may be altered when diagnosed, routine ophthalmic examination is still indicated.

The foot of Homo naledi.

Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot. The H. naledi foot is predominantly modern human-like in morphology and inferred function, with an adducted hallux, an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination, these features indicate a foot well adapted for striding bipedalism. However, the H. naledi foot differs from modern humans in having more curved proximal pedal phalanges, and features suggestive of a reduced medial longitudinal arch. Within the context of primitive features found elsewhere in the skeleton, these findings suggest a unique locomotor repertoire for H. naledi, thus providing further evidence of locomotor diversity within both the hominin clade and the genus Homo.

Increase of S-100 immunoreactivity in the urinary bladder from patients with multiple sclerosis, an indication of peripheral neuronal lesion.

The Schwann cells in urinary bladder biopsies from multiple sclerosis patients and controls were examined by immunocytochemistry with an antiserum to S-100. S-100 immunoreactivity was found to be markedly increased in these tissues as compared with the controls, indicating a Schwann cell hyperplasia in the urinary bladder in multiple sclerosis. This finding suggests that local neuronal damage exists in the urinary bladder of patients with multiple sclerosis. Therefore, the concept of multiple sclerosis as a disease wholly of the central nervous system should be reexamined.