Effect of peri-operative chemotherapy regimen on survival in the treatment of locally advanced oesophago-gastric adenocarcinoma - A comparison of the FLOT and 'MAGIC' regimens.

BACKGROUND: Peri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates. METHODS: Cohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas' Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells. RESULTS: Patients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50-0.94) and disease-free survival (HR = 0.75, 95% CI 0.58-0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups. CONCLUSIONS: Patients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable.

What Happens to Nutrition Intake in the Post-Intensive Care Unit Hospitalization Period? An Observational Cohort Study in Critically Ill Adults.

BACKGROUND: Little is currently known about nutrition intake and energy requirements in the post-intensive care unit (ICU) hospitalization period in critically ill patients. We aimed to describe energy and protein intake, and determine the feasibility of measuring energy expenditure during the post-ICU hospitalization period in critically ill adults. METHODS: This is a nested cohort study within a randomized controlled trial in critically ill patients. After discharge from ICU, energy and protein intake was quantified periodically and indirect calorimetry attempted. Data are presented as n (%), mean (SD), and median (interquartile range [IQR]). RESULTS: Thirty-two patients were studied in the post-ICU hospitalization period, and 12 had indirect calorimetry. Mean age and BMI was 56 (18) years and 30 (8) kg/m2 , respectively, 75% were male, and the median estimated energy and protein requirement were 2000 [1650-2550] kcal and 112 [84-129] g, respectively. Oral nutrition either alone (n = 124 days, 55%) or in combination with enteral nutrition (n = 96 days, 42%) was the predominant mode. Over 227 total days in the post-ICU hospitalization period, a median [IQR] of 1238 [869-1813] kcal and 60 [35-89.5] g of protein was received from nutrition therapy. In the 12 patients who had indirect calorimetry, the median measured daily energy requirement was 1982 [1843-2345] kcal and daily energy deficit was -95 [-1050 to 347] kcal compared with the measured energy requirement. CONCLUSIONS: Energy and protein intake in the post-ICU hospitalization period was less than estimated and measured energy requirements. Oral nutrition provided alone was the most common mode of nutrition therapy.

Nutrition Therapy in Australia and New Zealand Intensive Care Units: An International Comparison Study.

BACKGROUND: The Augmented Versus Routine Approach to Giving Energy Trial (TARGET) is the largest blinded enteral nutrition (EN) intervention trial evaluating energy delivery to be conducted in the critically ill. To determine the external validity of TARGET results, nutrition practices in intensive care units (ICUs) in Australia and New Zealand (ANZ) are described and compared with international practices. METHODS: This was a retrospective analysis of prospectively collected data for the International Nutrition Surveys, 2007-2013. Data are presented as mean (SD). RESULTS: A total of 17,154 patients (ANZ: n = 2776 vs international n = 14,378) from 923 ICUs (146 and 777, respectively) were included. EN was the most common route of feeding (ANZ: 85%, n = 2365 patients vs international: 84%, n = 12,034; P = .258), and EN concentration was also similar (<1.25 kcal/mL ANZ: 70%, n = 12,396 vs international: 65%, n = 56,891 administrations; P < .001). Protein delivery was substantially below the estimated prescriptions but similar between the regions (0.6 [0.4] g/kg/day vs 0.6 [0.4] g/kg/day; P = .849). Patients in ANZ received slightly more energy (1133 [572] vs 948[536] kcal/day; P < .001), possibly because more energy was prescribed (1947 [348] vs 1747 [376] kcal/day; P < .001), nutrition protocols were more commonly used (98% vs 75%; P < .001) and included recommendations for therapies such as prokinetic agents (87% vs 51%, n = 399; P < .001) and small bowel feeding (62% vs 40%; P < .001) when compared with international ICUs. CONCLUSIONS: Key elements of nutrition practice are similar in ANZ and international ICUs. These data can be used to determine the external validity and relevance of TARGET results.

Delivery of full predicted energy from nutrition and the effect on mortality in critically ill adults: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The amount of energy required to improve clinical outcomes in critically ill adults is unknown. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the impact of near target energy delivery to critically ill adults on mortality and other clinically relevant outcomes. DESIGN: Following PRISMA guidelines, MEDLINE, EMBASE, CINHAL and the Cochrane Library were searched for randomised controlled trials evaluating nutrition interventions in adult critical care populations. Included studies compared delivery of ≥80% of predicted energy requirements (near target) from enteral and/or parenteral nutrition to <80% (standard care) and reported mortality. The quality of individual studies was assessed using the Cochrane 'Risk of Bias' tool, and the overall body of evidence using the GRADE approach. Fixed or random effect meta-analyses were used pending the presence of heterogeneity (I2 > 50%) when 3 or more studies reported the same outcome. Outcomes are presented as risk ratio (RR), 95% confidence interval (CI). RESULTS: Ten trials with 3155 participants were included. Mortality was unaffected by the intervention (RR 1.02, 95% CI 0.81, 1.27, p = 0.89, I2 = 25%). Evaluation of studies of higher quality and low risk of bias did not alter the mortality inference (3 trials, 352 participants, RR 0.83, 95% CI 0.49, 1.40, p = 0.19, I2 = 39%). The quality of evidence across outcomes was very low. CONCLUSIONS: The delivery of near target energy when compared to standard care in adult critically ill patients was not associated with an effect on mortality. Because the quality of the evidence across outcomes was very low there is considerable uncertainty surrounding this estimate. This has implications for clinical utility of the evidence within the included reviews.

Full predicted energy from nutrition and the effect on mortality and infectious complications in critically ill adults: a protocol for a systematic review and meta-analysis of parallel randomised controlled trials.

BACKGROUND: Whilst nutrition is vital to survival in health, the precise role of nutrition during critical illness is controversial. More specifically, the exact amount of energy that is required during critical illness to optimally influence clinical outcomes remains unknown. The aim of this systematic literature review and meta-analysis is to evaluate the clinical effects of optimising nutrition to critically ill adult patients, such that the entire predicted amount of energy that the patient requires is delivered, on mortality and other important outcomes. METHODS: A systematic literature review and meta-analysis will be conducted by searching for studies indexed in Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Library. Searches will be restricted to English. Studies will be considered for inclusion if they are a parallel randomised controlled trial investigating a nutrition intervention in an adult critical care population, where one arm delivers 'full predicted energy from nutrition' (defined as provision of ≥80% of the predicted energy required) and the other arm delivers energy less than 80% of the predicted requirement. Two authors will independently perform title screening, full-text screening, data extraction and quality assessment for this review. The quality of individual studies will be assessed using the 'Risk of Bias' tool, and to assess the overall body of evidence, a 'Summary of Findings' table and the Grades of Recommendation, Assessment, Development and Evaluation system will be used, all recommended by the Cochrane Library. Pending the study heterogeneity that is determined, a fixed-effect meta-analysis with pre-defined subgroup analyses will be performed. DISCUSSION: Currently, it is controversial whether optimal energy delivery is beneficial for outcomes in critically ill patients. This systematic review and meta-analysis will evaluate whether delivering optimal energy to critically ill adult patients improves outcomes when compared to delivery of lesser amounts. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015027512.

Nutrition therapy in adult patients receiving extracorporeal membrane oxygenation: a prospective, multicentre, observational study.

OBJECTIVES: To describe current nutrition delivery practices and to identify barriers to nutrition in patients receiving venovenous or venoarterial extracorporeal membrane oxygenation (ECMO) in multiple centres in Australia and New Zealand. DESIGN, SETTING AND PARTICIPANTS: A prospective, multicentre, observational study, set in eight intensive care units in Australia and New Zealand, of adults treated with ECMO who were expected to receive enteral nutrition (EN) or parenteral nutrition (PN) therapy for > 72 hours. Data were collected from the start of ECMO until 7 days after ECMO cessation. RESULTS: There were 107 patients enrolled, with a median age of 42 years (interquartile range [IQR], 31-56 years), and 54 patients (50%) were men. EN was the most commonly delivered mode of nutrition (on 84% of days) although it was interrupted on 53% of days. The median interruption duration was 8 hours (IQR, 4-5 hours] per episode. The two most common barriers to EN delivery were fasting for a therapeutic or diagnostic procedure and high gastric residual volumes. Median daily calorie and protein deliveries from EN and/or PN were 1680 kcal (IQR, 960-2100 kcal) and 72 g (IQR, 42-98 g) of protein. For patients who received EN and/or PN, median calorie and protein deficits during the study period were -7118 kcal (IQR, -11 614 to -4510 kcal) and -325 g (IQR, - 525 to -188 g) of protein. CONCLUSIONS: EN was the most commonly used nutrition-delivery mode during ECMO treatment but was frequently interrupted. Compared with estimated calorie and protein requirements, lesser but reasonably acceptable amounts were delivered, although calorie and protein deficits still existed.

International consensus guidelines for nutrition therapy in pancreatitis.

Guidelines for nutrition support in pancreatitis have been inconsistently adapted to clinical practice. The International Consensus Guideline Committee (ICGC) established a pancreatitis task force to review published guidelines for pancreatitis in nutrition support. A PubMed search using the terms pancreatitis, acute pancreatitis, chronic pancreatitis, nutrition support, parenteral nutrition, enteral nutrition, and guidelines was conducted for the period from January 1999 to May 2011. Eleven guidelines were identified for review. The ICGC used the following process to develop unified guideline statements: summarize the strength of evidence (grading) of the guidelines; establish level of evidence for ICGC statements as high, intermediate, and low; assign published guideline levels of evidence; and define an ICGC grading system. International Pancreatitis Guideline Grades were established as follows: platinum-high level of evidence and consistent agreement among the guidelines; gold-acceptable level of evidence and no conflicting statements in guidelines; and silver-single existing guideline statement with no conflict in other guidelines. Eighteen ICGC statements were derived from the 11 published pancreatitis guidelines. Uniform agreement from widely disparate groups (United States, Europe, Japan, and China) resulted in 4 platinum-level guideline statements for nutrition in pancreatitis: nutrition support therapy (NST) is generally not needed for mild to moderate disease, NST is needed for severe disease, enteral nutrition (EN) is preferred over parenteral nutrition (PN), and use PN when EN is contraindicated or not feasible. This methodology provides a template for future ICGC nutrition guideline development.

Practicalities of nutrition support in the intensive care unit: the usefulness of gastric residual volume and prokinetic agents with enteral nutrition.

The provision of early nutrition therapy to critically ill patients is established as the standard of care in most intensive care units around the world. Despite the known benefits, tolerance of enteral nutrition in the critically ill varies and delivery is often interrupted. Observational research has demonstrated that clinicians deliver little more than half of the enteral nutrition they plan to provide. The main clinical tool for assessing gastric tolerance is gastric residual volume; however, its usefulness in this setting is debated. There are several strategies employed to improve the tolerance and hence adequacy of enteral nutrition delivery in the critically ill. One of the most widely used strategies is that of prokinetic drug administration, most commonly metoclopramide and erythromycin. Although there are new agents being investigated, none are ready for routine application in the critically ill and the benefits are still being established. This review investigates current practice and considers the literature on assessment of enteral tolerance and optimization of enteral nutrition in the critically ill.

Nutritional therapy in patients with acute pancreatitis requiring critical care unit management: a prospective observational study in Australia and New Zealand.

OBJECTIVE: To determine nutritional therapy practices of patients with severe acute pancreatitis (defined as those receiving critical care management in an intensive care unit or high-dependency unit) in Australia and New Zealand with focus on the choice of enteral nutrition or parenteral nutrition. DESIGN: Prospective observational multicentered study performed at 40 sites in Australia and New Zealand over 6 months. SETTING: Intensive care units or high-dependency units within Australia and New Zealand. PATIENTS: Those with severe acute pancreatitis diagnosed by elevated lipase and/or amylase. Patients with chronic pancreatitis were excluded. MEASUREMENTS: The primary outcome was the proportion of patients who received enteral nutrition, parenteral nutrition, or concurrent enteral nutrition/parenteral nutrition. Secondary outcomes included other aspects of nutritional therapy and the severity and clinical outcomes of acute pancreatitis. MEASUREMENTS AND MAIN RESULTS: We enrolled 121 patients and 117 were analyzed. The mean age was 61 (sd 17) years and 53% were men. Enteral nutrition was delivered to 58 (50%; 95% confidence interval [CI], 41-59%) and parenteral nutrition to 49 (42%; 95% CI, 33-51%) patients. Parenteral nutrition was more frequently used as the initial therapy (58%; 95% CI, 49-67%) than enteral nutrition (42%; 95% CI, 33-51%). The most common reason for parenteral nutrition prescription was the treating doctor's preference (60%). Enteral nutrition (74%) was more often used than parenteral nutrition (40%) on any individual study day. Concurrent enteral nutrition and parenteral nutrition occurred in 28 (24%) patients on 14% of days. Complications of acute pancreatitis requiring critical care unit management were observed in 45 (39%) patients. The median (interquartile range) duration of intensive care unit and hospital stay were 5 (2-10) and 19 (9-31) days, respectively. The hospital mortality rate was 15% (95% CI, 8-21%), and there was a tendency toward higher mortality for patients who only received parenteral nutrition than for those who only received enteral nutrition (28% vs. 7%, p=.06). CONCLUSIONS: For patients with acute pancreatitis requiring critical care unit management in Australian and New Zealand intensive care units, enteral nutrition is used most commonly, but parenteral nutrition is more often used as the initial route of nutritional therapy. Given that clinical practice guidelines currently recommend enteral nutrition as the initial route of nutritional therapy in severe acute pancreatitis, improved education about and dissemination of these guidelines seems warranted.

Creating a culture of clinical excellence in critical care nutrition: the 2008 "Best of the Best" award.

OBJECTIVE: To develop, validate, and implement a system to reward top performers in critical care nutrition practice and to illuminate characteristics of top-performing intensive care units (ICUs). DESIGN: An international, prospective, observational, cohort study conducted in May 2008. SETTING: 179 ICUs from 18 countries. PATIENTS: 2956 consecutively enrolled mechanically ventilated adult patients who stayed in the ICU for at least 72 hours. INTERVENTIONS: To qualify for the "Best of the Best" (BOB) award, sites had to have implemented a nutrition protocol and contributed complete data on a minimum of 20 patients. MEASUREMENTS AND MAIN RESULTS: Data on nutrition practices were collected from ICU admission to ICU discharge for a maximum of 12 days. Eligible sites were ranked based on their performance on the following 5 criteria: adequacy of provision of energy, use of enteral nutrition (EN), early initiation of EN, use of promotility drugs and small bowel feeding tubes, and adequate glycemic control. Of the 179 participating ICUs, 81 qualified for the BOB award. Overall, the average nutrition adequacy across sites was 56.2% (site range, 20.3%-90.1%). The top 10 performers were identified and publicly recognized. Regression analysis suggested that the presence of a dietitian in the ICU was associated with a high BOB award ranking, whereas being located in the United States or China, relative to other participating countries, was associated with worst performance. CONCLUSIONS: There is variable performance with respect to critical care nutrition practices across the world.

Practicalities of nutrition support in the intensive care unit.

PURPOSE OF REVIEW: Nutrition support improves clinical outcomes in the critically ill and our understanding of its effects has advanced significantly over the last few years. Three recently published evidence-based guidelines have made generally consistent and thorough recommendations to assist clinicians in providing nutrition support. This review will focus on various aspects of these recommendations, concentrating on the practicalities of nutrition support in the intensive care unit, such as its optimal mode and composition. RECENT FINDINGS: Enteral nutrition is preferred to parenteral nutrition unless there is a major gut condition which will delay commencement of enteral nutrition. Nasogastric feeding should begin within 24 h, but if intolerance develops, small bowel feeding or pro-motility drugs (erythromycin or metoclopramide) should be attempted before resorting to supplementary parenteral nutrition. Enteral nutrition should not routinely be supplemented with arginine or glutamine, but it should contain a package of eicosapentaenoic acid, gamma-linolenic acid and antioxidants if the patient has acute lung injury or sepsis. Parenteral nutrition should be glutamine supplemented and the prescription should be limited in energy to avoid hyperglycemia. Whether using enteral nutrition or parenteral nutrition, most patients should receive intravenous selenium, and may also need zinc and copper supplementation. SUMMARY: Intensive care unit patients should have nutrition support based on recent evidence-based guidelines with a preference for nasogastric feeding. If intolerance occurs, pro-motility drugs and small bowel feeding should be attempted. Clinicians should also consider carefully the composition of the nutrition support regimen with regard to lipid content (especially eicosapentaenoic acid and gamma-linolenic acid), antioxidants, glutamine and other micronutrients.