Association of metabolomic markers and response to nutritional support: A secondary analysis of the EFFORT trial using an untargeted metabolomics approach.

BACKGROUND & AIMS: The EFFORT trial reported a substantial risk reduction for adverse events and mortality in medical in-patients receiving a nutritional support intervention. With the use of an untargeted metabolomics approach, we investigated the prognostic and therapeutic potential of metabolomic markers to understand, whether there are distinct metabolic patterns associated with malnutrition risk as assessed by the Nutritional Risk screening (NRS 2002) score, the risk of 30-day mortality and the response to nutritional support, respectively. METHODS: Out of the 2088 samples we randomly selected 120 blood samples drawn on day 1 after hospital admission and before treatment initiation. Samples were stratified by NRS 2002, treatment allocation (intervention vs. control), and mortality at 30 days, but not on the type of medical illness. We performed untargeted analysis by liquid chromatography mass spectrometry (LC-MS/MS). RESULTS: We measured 1389 metabolites in 120 patients of which 81 (67.5%) survived until day 30. After filtering, 371 metabolites remained, and 200 were matched to one or more Human Metabolome Data Base (HMDB) entries. Between group analysis showed a slight distinction between the treatment groups for patients with a NRS 3, but not for those with NRS 4 and ≥ 5. C-statistic between those who died and survived at day 30 ranged from 0.49 (95% confidence interval 0.35-0.68) for a combination of 5 metabolites/predictors to 0.66 (95% confidence interval 0.53-0.79) for a combination of 100 metabolites. Pathway analysis found significant enrichment in the pathways for nitrogen, vitamin B3 (nicotinate and nicotinamide), leukotriene, and arachidonic acid metabolisms in nutritional support responders compared to non-responders. CONCLUSION: In our heterogenous population of medical inpatients with different illnesses and comorbidities, metabolomic markers showed little prognostic and therapeutic potential for better phenotyping malnutrition and response to nutritional therapy. Future studies should focus on more selected patient populations to understand whether a metabolomic approach can advance the nutritional care of patients.

Influence of nutritional assistance on mortality by COVID-19 in critically ill patients.

BACKGROUND & AIMS: Evidence suggests the existence of an association between the institution of nutritional therapy and clinical outcomes in patients with critical COVID-19. Thus, the aim of this study was to evaluate the influence of nutritional assistance on COVID-19 mortality in patients admitted to intensive care units (ICU). METHODS: This is a subset of the cohort "Influence of nutritional therapy on clinical prognosis in patients with COVID-19: a multicenter retrospective cohort study". Clinical and nutrition assistance information (type of assistance, evaluation of anthropometric status, and time of introduction of nutritional therapy) and presence of diabetes, hypertension and previous respiratory disease were collected from electronic medical records. To evaluate the association between the variables of interest and mortality, the hazard ratio was estimated. RESULTS: We evaluated 153 critically ill patients ≥18 years old, affected by COVID-19, with a rate of mortality of 77.8%. Among non survivors 58.8% were female, 52.9% aged <65 years, 66.4% had arterial hypertension, 46.2% diabetes mellitus and 81.5% had an early onset of nutritional support. Initiation of nutritional therapy after 48 h (HR: 2.57; 95% CI: 1.57-4.20) and the presence of obesity (HR: 1.55; 95% CI: 1.04-2.31) were associated with higher mortality, even after adjustment for potential confounders. CONCLUSIONS: Our data suggests that the provision of early nutritional therapy should be prioritized, with greater attention directed to obese patients, and the nutritional assistance can contribute favorably to the clinical evolution and prognosis of critically ill patients with COVID-19.

Hyponatremia is a Prognostic Factor in Patients Receiving Nutrition Support.

BACKGROUND: Hyponatremia, the most common electrolyte disorder, has been reported to be related to increased mortality. However, the association between hyponatremia and prognoses remains unclear in patients with nutrition support team (NST) intervention. This study aimed to determine the prevalence of abnormal serum sodium levels, its relation to patient data, and the impact of hyponatremia on prognosis. METHODS: Patients who received nutrition support at Tokushima University Hospital for the first time and whose serum sodium levels were measured at the start of NST intervention were enrolled. Patients were classified into three groups according to their serum Na levels at the start of NST intervention: hyponatremia group, normonatremia group, and hypernatremia group. RESULTS: In the hyponatremia group compared to the normonatremia group, body weight and body mass index were significantly lower. C-reactive protein levels and urea nitrogen/creatinine ratios were significantly higher. Meanwhile, there was no significant difference in the estimated glomerular filtration rate among the groups. The prevalence of malnutrition and anemia were the highest in the hyponatremia group. The 3-year survival rate was approximately 45% in the hyponatremia group, which was the lowest of all three groups. The mortality risk ratio of the hyponatremia group to the normonatremia group was 2.29. CONCLUSIONS: Hyponatremia in NST intervention patients is an independent prognostic predictor. Therefore, adding an assessment of serum sodium at the beginning of NST intervention can identify patients at high risk at an early stage and may improve the quality of NST activity.

TICACOS international: A multi-center, randomized, prospective controlled study comparing tight calorie control versus Liberal calorie administration study.

Since the first TICACOS study, 3 additional studies have been published comparing a medical nutrition therapy guided by indirect calorimetry to a regimen prescribed on the basis of predictive equations. A recent guidelines document included a meta-analysis including these 4 papers and found a trend for improvement (OR 0.98-1.48) in favor of medical nutrition therapy guided by indirect calorimetry in terms of survival. The aim of our study was to perform a multicenter prospective, randomized, controlled non blinded study in critically patients to assess the added value for measuring daily resting energy expenditure as a guide for nutritional support. The primary objective was to decrease infectious rate of these critically ill patients. MATERIAL AND METHODS: This phase III, multi-center, randomized, controlled non blinded study was planned to include 580 newly-admitted, adult ventilated ICU patients that were planned to stay more than 48 h in the ICU departments. The nutritional support was aimed to meet 80-100% of energy requirement measured by indirect calorimetry. The calorie needs were determined by IC in the Study group and by an equation (20-25 kcal/kg ideal body weight/day) in the Control Group. The ICU staff was trained to strive to supply 80-100% of a patient's energy requirements through artificial nutrition, preferably enteral feeding. Primary endpoint was infection rate and secondary endpoints included other morbidities and mortality during ICU, at 90 and 180 days. Comparison between the study and the control group was performed using T test for equality of means (independent samples test). Correlations were performed using the Pearson correlation test. A p level of 0.05 or below was considered as significant. Cross tabs procedure used Chi-square test for testing differences in complication rates, length of stay and length of ventilation. Correlations between energy balances and complications was also be tested using one way analysis as well as ANOVA analysis between groups and within groups. Kaplan Meir curves assessed the proportion of surviving patients in the 2 groups. RESULTS: Seven centers with a calorimeter available participated to the study. Due to slow inclusion rate, the study was stopped after 6 years and after inclusion of 417 patients only. From the 417 intended to treat patients, 339 followed the protocol. There was no differences between control and study groups in terms of age, sex BMI, SOFA (7.1 ± 3.1 vs 7.4 ± 3.3) and APACHE II scores (22.4 ± 7.9 vs 22.2 ± 7.4). The rate of infection (40 vs 31), including pneumonia rate, need for surgery, dialysis requirement, length of ventilation, ICU length of stay, and hospital length of stay were not different between groups. Mortality (30 in the control vs 21 in the study group) was not significantly different between groups. The decreased mortality observed in the study group when added to previous studies may have a positive effect on the meta-analysis previously published. CONCLUSION: Tight Calorie Control guided by indirect calorimetry decreased the rate of infection and mortality but not significantly. This may be explained by the not relatively small sample size. There results together with the previous 4 prospective randomized studies, may improve the results of the meta-analysis exploring the effects of IC guided nutrition on mortality.

Association between nutrition support and acute gastrointestinal injury in critically ill patients during the first 72 hours.

BACKGROUND & AIMS: The impact of nutrition support on patients with acute gastrointestinal injury (AGI) has not been fully determined. This study aimed to 1) investigate the relationship between nutrition support and AGI, as well as nutrition support and prognosis in critically ill AGI patients and 2) evaluate the prognostic benefits of nutrition support in different severity categories of AGI patients. METHODS: This prospective study included 379 patients in whom AGI occurred in the first 72 h after admission from 12 teaching hospitals in China. Clinical characteristics including demographics, APACHE II score, modified NUTRIC score, SOFA score, calories of nutrition, and 7 and 28-day mortality were recorded. Multiple logistic regression analysis was applied to identify the risk factors for mortality. The survival benefit of nutrition support as reflected by calories of nutrition in 72 h was evaluated for patients categorized according to their APACHE II, modified NUTRIC, and SOFA scores. RESULTS: Patients were classified into Grades I (n = 141), II (n = 173), III (n = 48), and IV (n = 17). Significant differences were observed among different AGI grade cohorts (I-IV) in terms of APACHE II, SOFA, and modified NUTRIC scores and calories of enteral nutrition (EN), parenteral nutrition (PN), and EN + PN. Ordinal logistic regression analysis showed that only SOFA score was an independent risk factor for AGI grades (P < 0.001). APACHE II score, mechanical ventilation (MV), AGI grades, and calories of EN + PN intake were independent risk factors for 28-d mortality. Increased nutritional intake was associated with reduced mortality in severely ill patients with APACHE II scores ≥15 (P = 0.007). CONCLUSIONS: AGI grade affected the intake of calories and was one of the risk factors for 28-d mortality. The nutrition intake of patients with AGI grade III to IV was almost only PN. The positive association between nutrition support and prognosis was more apparent in AGI patients with higher APACHE II scores.

Nutritional support and clinical outcomes in critically ill patients supported with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND & AIMS: Patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are likely to be develop malnutrition because of catabolism and protein consumption. Administration of appropriate nutrition to these patients is difficult because of hemodynamic instability and multiorgan failure. The aim of this study was to evaluate the relationship between nutritional supply and clinical outcomes in patients undergoing VA-ECMO. METHODS: Patients who received VA-ECMO in a single tertiary teaching hospital between 2013 and 2018 were reviewed retrospectively. Linear regression and Cox regression were performed to assess the relationship between the following factors and clinical outcomes: sex, age, BMI, modified nutrition risk in the critically ill (mNUTRIC) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, ENCOURAGE score, daily average achievement of an energy target (%), and average protein intake during the first week and second week. RESULTS: Forty-one patients were included. Patients on VA-ECMO received lower amounts of energy and protein in the first week than in the second week (33.9 vs 77.7% target/day, 0.24 vs. 0.74 g/kg/day) and achieved 70% of their energy requirement at a median of 8 days after the initiation of VA-ECMO. Multiple Cox regression analysis revealed an association among energy received daily during the second week of VA-ECMO, mNUTRIC score, and 90-day mortality (hazard ratio, 0.82, 95% confidence interval [0.69-0.97], P = 0.018 vs. hazard ratio, 1.51, 95% confidence interval [1.06-2.15], P = 0.022). CONCLUSION: In VA-ECMO patients, when the daily average energy intake increased by 10% of the target over 8-14 days, the 90-day mortality decreased by 18%.

Outcome of Very Preterm Infants With Early Optimal Nutrition Strategy: A Comparative Cohort Study.

BACKGROUND: Aggressive nutrition may benefit early growth; nevertheless, effects on neurodevelopmental outcomes are unclear. We planned a descriptive analytical study to compare survival without neurodevelopment disability (NDD) at 1 year in 2 groups during 2 time epochs-before and after implementation of early optimal nutrition strategies. NDD was defined as any one of the following: mental and/or motor development quotient < 85 at 12 months of age, corrected for prematurity; Denver Developmental Screening Test abnormal/suspect in even 1 domain out of the 4 domains; seizures; requirement of hearing aid; or blindness in 1 or both eyes. We also compared mortality, survival without bronchopulmonary dysplasia, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage, periventricular leukomalacia, sepsis, metabolic bone disease (MBD), and extrauterine growth restriction (EUGR). METHODS: Preterm neonates born between 27 and 32 weeks' gestation were included. The prospective study group (AO) was recruited after implementation of early optimal nutrition policy. The comparative retrospective cohort (BO) received nutrition based on clinicians' decisions. Both groups were followed up using a structured plan till 1 year corrected age. RESULTS: 137 neonates were enrolled in AO and 151 in the BO cohort. There was no statistically significant difference in survival without NDD at 1 year-75.5% in AO vs 72.1% in BO, odds ratio 0.84 (95% CI 0.5-1.6). Babies who received early optimal nutrition had less NEC, EUGR, and ROP requiring laser therapy but more MBD. CONCLUSION: There was no difference in survival without NDD in early optimal nutrition cohort compared to the cohort before implementation of the nutrition strategy. Short-term benefits themselves may justify the need for early optimal nutrition.

Relationship between Nutrition Intake and 28-Day Mortality Using Modified NUTRIC Score in Patients with Sepsis.

In critically ill patients, malnutrition is known to increase morbidity and mortality. We investigated the relationship between nutritional support and 28-day mortality using the modified NUTrition RIsk in the Critically ill (NUTRIC) score in patients with sepsis. This retrospective cohort study included patients with sepsis admitted to the medical intensive care unit (ICU) between January 2011 and June 2017. Nutritional support for energy and protein intakes at day 7 of ICU admission were categorized into <20, 20 to <25, and ≥25 kcal/kg and <1.0, 1.0 to <1.2, and ≥1.2 g/kg, respectively. NUTRIC scores ≥4 were considered to indicate high nutritional risk. Among patients with low nutritional risk, higher intakes of energy (≥25 kcal/kg) and protein (≥1.2 g/kg) were not significantly associated with lower 28-day mortality. In patients with high nutritional risk, higher energy intakes of ≥25 kcal/kg were significantly associated with lower 28-day mortality compared to intakes of <20 kcal/kg (adjusted hazard ratio (aHR): 0.569, 95% confidence interval (CI): 0.339-0.962, p = 0.035). Higher protein intakes of ≥1.2 g/kg were also significantly associated with lower 28-day mortality compared to intakes of <1.0 g/kg (aHR: 0.502, 95% CI: 0.280-0.900, p = 0.021). Appropriate energy (≥25 kcal/kg) and protein (≥1.2 g/kg) intakes during the first week may improve outcomes in patients with sepsis having high nutritional risk.

Assessment and outcome of pediatric intestinal pseudo-obstruction: A tertiary-care-center experience from Turkey.

BACKGROUND/AIMS: Pediatric intestinal pseudo-obstruction (PIPO) is a severe disorder of gut motility. In this rare and difficult-to-manage disease, complex treatment method, such as intestinal transplantation, is sometimes needed. This study evaluated the management and follow-up results of patients with PIPO who received treatment at our center. MATERIALS AND METHODS: The cases of 13 patients with PIPO were reviewed retrospectively. Demographic data, clinical features, etiologies, pharmacological and surgical treatments, nutritional support, anthropometric findings, small bowel transplantation (SBT), and survival rates were assessed. RESULTS: Two of the patients were diagnosed at 1 and 5 years of age, while other patients were diagnosed during neonatal period. The etiological cause could not be identified for 5 patients. Pharmacological treatment response was observed in 38.4% of patients. Post-pyloric feeding was applied in 4 patients, but no response was observed. Gastrostomy decreased the clinical symptoms in 3 patients during the abdominal distension period. Total oral nutrition was achieved in 38.4% of the total-parenteral-nutrition (TPN)-dependent patients. It was observed that anthropometric findings improved in patients with total oral nutrition. Liver cirrhosis developed in 1 patient. Venous thrombosis developed in 4 patients. The SBT was performed on 3 patients. One of these patients has been followed up for the last 4 years. CONCLUSION: Pediatric intestinal pseudo-obstruction is a rare disease that can present with a wide range of clinical symptoms. While some patients require intestinal transplantation, supportive care may be sufficient in others. For this reason, patients with PIPO should be managed individually.

Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study.

BACKGROUND & AIMS: Optimal protein intake during critical illness is unknown. Conflicting results on nutritional support during the first week of ICU stay have been published. We addressed timing of protein intake and outcomes in ICU patients requiring prolonged mechanical ventilation. METHODS: We retrospectively collected nutritional and clinical data on the first 7 days of ICU admission of adult critically ill patients, who were mechanically ventilated in our ICU for at least 7 days and admitted between January 1st 2011 and December 31st 2015. Based on recent literature, patients were divided into 3 protein intake categories, <0.8 g/kg/day, 0.8-1.2 g/kg/day and >1.2 g/kg/day. Our primary aim was to identify the optimum protein dose and timing related to the lowest 6 month mortality. Secondary endpoints were ventilation duration, need for renal replacement therapy (RRT), ICU length of stay (LOS) and mortality and hospital LOS and mortality. RESULTS: In total 455 patients met the inclusion criteria. We found a time-dependent association of protein intake and mortality; low protein intake (<0.8 g/kg/day) before day 3 and high protein intake (>0.8 g/kg/day) after day 3 was associated with lower 6-month mortality, adjusted HR 0.609; 95% CI 0.480-0.772, p < 0.001) compared to patients with overall high protein intake. Lowest 6-month mortality was found when increasing protein intake from <0.8 g/kg/day on day 1-2 to 0.8-1.2 g/kg/day on day 3-5 and >1.2 g/kg/day after day 5. Moreover, overall low protein intake was associated with the highest ICU, in-hospital and 6-month mortality. No differences in ICU LOS, need for RRT or ventilation duration were found. CONCLUSIONS: Our data suggest that although overall low protein intake is associated with the highest mortality risk, high protein intake during the first 3-5 days of ICU stay is also associated with increased long-term mortality. Therefore, timing of high protein intake may be relevant for optimizing ICU, in-hospital and long-term mortality outcomes.

Combination of apatinib and continuous nutritional support for a gastric cancer patient with brain metastasis prolongs survival.

WHAT IS KNOWN AND OBJECTIVES: Gastric cancer is the most common gastrointestinal malignant tumour in China, which rarely metastasizes into the central nervous system. However, brain metastasis leads to increased risk of death. CASE SUMMARY: Here, we report a case of brain metastasis from gastric cancer, which was treated with apatinib and continual nutritional support, with a survival time of 2 years. WHAT IS NEW AND CONCLUSION: The combination of apatinib and continual nutritional support may be an option for the treatment of brain metastasis from gastric cancer. A prospective study should be performed to confirm this.

Nutritional Status and Nutritional Treatment Are Related to Outcomes and Mortality in Older Adults with Hip Fracture.

Malnutrition is very prevalent in geriatric patients with hip fracture. Nevertheless, its importance is not fully recognized. The objective of this paper is to review the impact of malnutrition and of nutritional treatment upon outcomes and mortality in older people with hip fracture. We searched the PubMed database for studies evaluating nutritional aspects in people aged 70 years and over with hip fracture. The total number of studies included in the review was 44, which analyzed 26,281 subjects (73.5% women, 83.6 ± 7.2 years old). Older people with hip fracture presented an inadequate nutrient intake for their requirements, which caused deterioration in their already compromised nutritional status. The prevalence of malnutrition was approximately 18.7% using the Mini-Nutritional Assessment (MNA) (large or short form) as a diagnostic tool, but the prevalence was greater (45.7%) if different criteria were used (such as Body Mass Index (BMI), weight loss, or albumin concentration). Low scores in anthropometric indices were associated with a higher prevalence of complications during hospitalization and with a worse functional recovery. Despite improvements in the treatment of geriatric patients with hip fracture, mortality was still unacceptably high (30% within 1 year and up to 40% within 3 years). Malnutrition was associated with an increase in mortality. Nutritional intervention was cost effective and was associated with an improvement in nutritional status and a greater functional recovery. To conclude, in older people, the prevention of malnutrition and an early nutritional intervention can improve recovery following a hip fracture.

Should We Prescribe More Protein to Critically Ill Patients?

In the context of critical illness, evidence suggests that exogenous protein/amino acid supplementation has the potential to favorably impact whole-body protein balance. Whether this translates into retention of muscle, greater muscle strength, and improved survival and physical recovery of critically ill patients remains uncertain. The purpose of this brief commentary is to provide an overview of the clinical evidence for and against increasing protein doses and to introduce two new trials that will add considerably to our evolving understanding of protein requirements in the critically ill adult patient.

Enteral and parenteral nutrition in cancer patients: a systematic review and meta-analysis.

BACKGROUND: In cancer patients, weight loss is an ominous sign suggesting disease progression and shortened survival time. As a result, providing nutrition support for cancer patients has been proposed as a logical approach for improving clinical outcomes. Nutrition support can be given to patients through enteral nutrition (EN) or parenteral nutrition (PN). The purpose of the review was to compare the outcomes of PN and EN in cancer patients. METHODS: A literature search was conducted in Ovid MEDLINE and OLDMEDLINE, Embase Classic and Embase, and Cochrane Central Register of Controlled Trials. Studies were included if over half of the patient population had cancer and reported on any of the following endpoints: the percentage of patients that experienced no infection, nutrition support complications, major complications or mortality. Risk ratios (RR) and 95% confidence intervals (CIs) using Review Manager Version 5.3 were calculated. Primary endpoints were stratified according to type of EN for subgroup analysis, grouping studies into either tube feeding (TF) or standard care (SC). Additionally, another subgroup analysis was conducted comparing studies with protein-energy malnutrition (PEM) patients and studies without PEM patients. RESULTS: The literature search yielded 674 articles of which 36 were included for the meta-analysis. There were no difference in the endpoints between the two study interventions except that PN resulted in more infection when compared with EN (RR =1.09, 95% CI: 1.01-1.18; P=0.03). CONCLUSIONS: Other than increased incidence of infection, PN has not resulted in prolonging the survival, increasing nutrition support complications, or major complications when compared with EN in cancer patients.

Oedema is associated with clinical outcome following emergency abdominal surgery.

INTRODUCTION: Oedema is observed frequently following surgery and may be associated with worse outcomes. To date, no study has investigated the role of oedema in the emergency surgical patient. This study assesses the incidence of oedema following emergency abdominal surgery and the value of early postoperative oedema measurement in predicting clinical outcome. METHODS: A prospective cohort study of patients undergoing emergency abdominal surgery at a university unit over a two-month period was undertaken. Nutritional and clinical outcome data were collected and oedema was measured in the early postoperative period. Predictors of oedema and outcomes associated with postoperative oedema were identified through univariate and multivariate analysis. RESULTS: Overall, 55 patients (median age: 66 years) were included in the study. Postoperative morbidity included ileus (n=22) and sepsis (n=6) with 12 deaths at follow-up. Postoperative oedema was present in 19 patients and was associated with prolonged perioperative fasting (107 vs 30 hours, p=0.009) but not with body mass index (24 kg/m(2) vs 27 kg/m(2), p=0.169) or preadmission weight loss (5% vs 3%, p=0.923). On multivariate analysis, oedema was independently associated with gastrointestinal recovery (B=6.91, p=0.038), artificial nutritional support requirement (odds ratio: 6.91, p=0.037) and overall survival (χ(2) =13.1, df=1, p=0.001). CONCLUSIONS: Generalised oedema is common after emergency abdominal surgery and appears to independently predict gastrointestinal recovery, the need for artificial nutritional support and survival. Oedema is not associated with commonly applied markers of nutritional status such as body mass index or recent weight loss. Measurement of oedema offers utility in identifying those at risk of poor clinical outcome or those requiring artificial nutritional support following emergency abdominal surgery.

Nutritional support teams increase percutaneous endoscopic gastrostomy uptake in motor neuron disease.

AIM: To examine factors influencing percutaneous endoscopic gastrostomy (PEG) uptake and outcomes in motor neuron disease (MND) in a tertiary care centre. METHODS: Case notes from all patients with a confirmed diagnosis of MND who had attended the clinic at the Repatriation General Hospital between January 2007 and January 2011 and who had since died, were audited. Data were extracted for demographics (age and gender), disease characteristics (date of onset, bulbar or peripheral predominance, complications), date and nature of discussion of gastrostomy insertion, nutritional status [weight measurements, body mass index (BMI)], date of gastrostomy insertion and subsequent progress (duration of survival) and quality of life (QoL) [Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)]. In addition, the type of clinician initiating the discussion regarding gastrostomy was recorded as Nutritional Support Team (involved in providing nutrition input viz Gastroenterologist, Speech Pathologist, Dietitian) and other (involved in non-nutritional aspects of patient care). Factors affecting placement and outcomes including length of survival, change in weight and QoL were determined. RESULTS: Case records were available for all 86 patients (49 men, mean age at diagnosis 66.4 years). Thirty-eight patients had bulbar symptoms and 48 had peripheral disease as their presenting feature. Sixty-six patients reported dysphagia. Thirty-one patients had undergone gastrostomy insertion. The major indications for PEG placement were dysphagia and weight loss. Nine patients required immediate full feeding, whereas 17 patients initially used the gastrostomy to supplement oral intake, 4 for medication administration and 1 for hydration. Initially the PEG regime met 73% ± 31% of the estimated total energy requirements, increasing to 87% ± 32% prior to death. There was stabilization of weight in patients undergoing gastrostomy [BMI at 3 mo (22.6 ± 2.2 kg/m(2)) and 6 mo (22.5 ± 2.0 kg/m(2)) after PEG placement compared to weight at the time of the procedure (22.5 ± 3.0 kg/m(2))]. However, weight loss recurred in the terminal stages of the illness. There was a strong trend for longer survival from diagnosis among MND in PEG recipients with limb onset presentation compared to similar patients who did not undergo the procedure (P = 0.063). Initial discussions regarding PEG insertion occurred earlier after diagnosis when seen by nutrition support team (NST) clinicians compared to other clinicians. (5.4 ± 7.0 mo vs 11.9 ± 13.4 mo, P = 0.028). There was a significant increase in PEG uptake (56% vs 24%, P = 0.011) if PEG discussions were initiated by the NST staff compared to other clinicians. There was no change in the ALSFRS-R score in patients who underwent PEG (pre 34.1 ± 8.6 vs post 34.8 ± 7.4), although in non-PEG recipients there was a non-significant fall in this score (33.7 ± 7.9 vs 31.6 ± 8.8). Four patients died within one month of the procedure, 4 developed bacterial site infection requiring antibiotics and 1 required endoscopic therapy for gastric bleeding. Less serious complications attributed to the procedure included persistent gastrostomy site discomfort, poor appetite, altered bowel function and bloating. CONCLUSION: Initial discussion with NST clinicians increases PEG uptake in MND. Gastrostomy stabilizes patient weight but weight loss recurs with advancing disease.

Impact of nutritional factors on survival in patients with inoperable oesophageal cancer undergoing self-expanding metal stent insertion.

BACKGROUND: Undernutrition has been shown to be predictive of 30-day mortality in patients undergoing self-expanding metal stent (SEMS) insertion for inoperable oesophageal cancer. The aim of this study was to assess the relationship between nutritional factors and 30-day mortality in patients undergoing SEMS insertion for palliation of oesophageal cancer. METHODS: A retrospective cohort study was conducted from April 2007 to June 2009. BMI, swallowing ability, calorific intake and nature of nutritional support were recorded. ICD-10 causes of death were obtained from the Department of Health and Social Services. RESULTS: Fifty-six stents were inserted into 53 patients (mean age 70 years, male n=35). Median (interquartile range) BMI was 21.0 kg/m (18.7-24.0). Median pre-SEMS swallowing grade was 3. Median calorific intake as a percentage of estimated daily requirements was 94.0% (75.6-100.0%). Thirty (56.6%) patients tolerated an oral diet enhanced with supplement drinks whereas 23 (43.4%) patients required more invasive forms of enteral and parenteral support. The 30-day mortality rate was 11.3% (n=6) and cumulative median survival was 84 (interquartile range 38-156) days. BMI, calorific intake and swallowing capacity were not predictors of survival. Although there was a nonsignificant trend for reduced survival in those patients who did (n=23) receive invasive nutritional support compared with those who did not (n=30) (83.9 vs. 151.3 days, P=0.053), invasive nutritional support itself was not predictive of 30-day mortality (P=0.74). CONCLUSION: The requirement for invasive nutritional support before SEMS insertion is associated with a poor prognosis and possibly represents more aggressive tumour pathology. Further prospective assessment of prognostic factors, including nutritional parameters, to facilitate reliable selection of appropriate palliative modalities in oesophageal cancer is required.

Death, morbidity and economics are the only end points for trials.

In order to determine whether surrogate markers predict clinical outcome, randomized controlled trials (RCT) of nutrition support v. no nutrition support that have reported at least one clinical outcome (mortality, infections, total complications, or duration of hospitalization) and at least one nutritional outcome (energy or protein intake, weight gain, N balance, albumin, prealbumin, transferrin, three anthropometric measures, skin testing, lymphocyte count) were assessed for concordance. If changes in nutritional markers predict clinical outcome, changes in both outcomes should go in the same direction. Concordance is defined as both outcomes changing in the same direction or both outcomes showing no difference. Discordance is defined as one outcome changing and the other not (partial) or both outcomes changing in opposite directions (complete). Ninety-nine RCT were identified, of which most were underpowered to see statistically significant changes, especially in clinical outcomes. Thus, the results were analysed only in relation to the direction of the respective changes in outcomes. Forty-eight comparisons (4 x 12) were made. The rates of concordance were < or =50% in forty-one of forty-eight comparisons; the rate was never >75%. A complete discordance rate of > or =25% was present in forty-three (> or =50% in thirteen) of the forty-eight comparisons. The discordance was usually a result of the nutritional outcome being better than the clinical outcome. Changes in nutritional markers do not predict clinical outcomes. Before adopting any surrogate marker as an end point for a clinical trial, it has to be known that improving it will result in patient benefit.

Physiological functions should be considered as true end points of nutritional intervention studies.

With the beginning of this millennium it has become fashionable to only follow 'evidence-based' practices. This generally-accepted approach cruelly negates experience or intelligent interpretation of pathophysiology. Another problem is that the great 'meta-analysts' of the present era only accept end points that they consider 'hard'. In the metabolic and nutritional field these end points are infection-related morbidity and mortality, and all other end points are considered 'surrogate'. The aim of this presentation is to prove that this claim greatly negates the contribution of more-fundamentally-oriented research, the fact that mortality has multifactorial causes, and that infection is a crude measure of immune function. The following problems should be considered: many populations undergoing intervention have low mortality, requiring studies with thousands of patients to demonstrate effects of intervention on mortality; nutrition is only in rare cases primary treatment, and in many populations is a prerequisite for survival rather than a therapeutic modality; once the effect of nutritional support is achieved, the extra benefit of modulation of the nutritional support regimen can only be modest; cost-benefit is not a valid end point, because the better it is done the more it will cost; morbidity and mortality are crude end points for the effect of nutritional intervention, and are influenced by many factors. In fact, it is a yes or no factor. In the literature the most important contributions include new insights into the pathogenesis of disease, the diminution of disease-related adverse events and/or functional improvement after therapy. In nutrition research the negligence of these end points has precluded the development and validation of functional end points, such as muscle, immune and cognitive functions. Disability, quality of life, morbidity and mortality are directly related to these functional variables. It is, therefore, of paramount importance to validate functional end points and to consider them as primary rather than surrogate end points.