Proteins and amino acids are fundamental to optimal nutrition support in critically ill patients.

Proteins and amino acids are widely considered to be subcomponents in nutritional support. However, proteins and amino acids are fundamental to recovery and survival, not only for their ability to preserve active tissue (protein) mass but also for a variety of other functions. Understanding the optimal amount of protein intake during nutritional support is therefore fundamental to appropriate clinical care. Although the body adapts in some ways to starvation, metabolic stress in patients causes increased protein turnover and loss of lean body mass. In this review, we present the growing scientific evidence showing the importance of protein and amino acid provision in nutritional support and their impact on preservation of muscle mass and patient outcomes. Studies identifying optimal dosing for proteins and amino acids are not currently available. We discuss the challenges physicians face in administering the optimal amount of protein and amino acids. We present protein-related nutrition concepts, including adaptation to starvation and stress, anabolic resistance, and potential adverse effects of amino acid provision. We describe the methods for assessment of protein status, and outcomes related to protein nutritional support for critically ill patients. The identification of a protein target for individual critically ill patients is crucial for outcomes, particularly for specific subpopulations, such as obese and older patients. Additional research is urgently needed to address these issues.

Healthcare resource utilization and costs among patients with alpha-1 antitrypsin deficiency with liver and/or lung disease: a longitudinal retrospective study in the USA.

Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1 July 2021 to 31 January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90 days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.

Mortality among patients who receive or defer gastrostomies.

BACKGROUND & AIMS: There are few data on outcomes and mortality of patients who have received gastrostomies. We assessed 30-day and 1-year mortalities of patients in the United Kingdom who were referred to hospitals for gastrostomies and of patients who deferred this intervention. METHODS: We collected data from 1327 patients referred to 2 hospitals in Sheffield, United Kingdom, for gastrostomies from February 2004 through May 2010. Data were analyzed to determine 30-day and 1-year mortalities. Predicted mortality by using the validated Sheffield Gastrostomy Scoring System (SGSS) was then compared with actual mortality by using area under the receiver operator curves to determine levels of agreement in patients referred for gastrostomy. RESULTS: Three hundred four patients (23%) did not undergo gastrostomy after multidisciplinary team discussion, which was based on physicians' recommendations. This group had 35.5% mortality at 30 days and 74.3% at 1 year, whereas mortality among patients who underwent gastrostomy (n = 1027) was 11.2% at 30 days and 41.1% at 1 year (P < .0001, compared with patients who deferred the procedure). The area under the receiver operator curves for the SGSS demonstrated acceptable agreement between predicted and actual mortality in patients who underwent or were deferred gastrostomy. CONCLUSIONS: On the basis of data from 1327 patients, those who undergo gastrostomy have significantly lower mortality than those who defer the procedure. Without applying the SGSS, clinicians are able to select patients most likely to benefit from gastrostomy. The SGSS could provide objective support to clinicians involved in making ethically contentious or potentially litigious decisions.

Machine learning using longitudinal prescription and medical claims for the detection of non-alcoholic steatohepatitis (NASH).

OBJECTIVES: To develop and evaluate machine learning models to detect patients with suspected undiagnosed non-alcoholic steatohepatitis (NASH) for diagnostic screening and clinical management. METHODS: In this retrospective observational non-interventional study using administrative medical claims data from 1 463 089 patients, gradient-boosted decision trees were trained to detect patients with likely NASH from an at-risk patient population with a history of obesity, type 2 diabetes mellitus, metabolic disorder or non-alcoholic fatty liver (NAFL). Models were trained to detect likely NASH in all at-risk patients or in the subset without a prior NAFL diagnosis (at-risk non-NAFL patients). Models were trained and validated using retrospective medical claims data and assessed using area under precision recall curves and receiver operating characteristic curves (AUPRCs and AUROCs). RESULTS: The 6-month incidences of NASH in claims data were 1 per 1437 at-risk patients and 1 per 2127 at-risk non-NAFL patients . The model trained to detect NASH in all at-risk patients had an AUPRC of 0.0107 (95% CI 0.0104 to 0.0110) and an AUROC of 0.84. At 10% recall, model precision was 4.3%, which is 60× above NASH incidence. The model trained to detect NASH in the non-NAFL cohort had an AUPRC of 0.0030 (95% CI 0.0029 to 0.0031) and an AUROC of 0.78. At 10% recall, model precision was 1%, which is 20× above NASH incidence. CONCLUSION: The low incidence of NASH in medical claims data corroborates the pattern of NASH underdiagnosis in clinical practice. Claims-based machine learning could facilitate the detection of patients with probable NASH for diagnostic testing and disease management.

Enteral feeding in the critically ill: the role of the gastroenterologist.

Expertise in enteral nutrition (EN) is an important aspect of the skill set of the clinical gastroenterologist. Delivery of adequate EN in critically ill patients is an active therapy that attenuates the metabolic response to stress and favorably modulates the immune system. EN is less expensive than parenteral nutrition and is favored in most cases because of improvement in patient outcomes, including infections and length of stay. Newer endoscopic techniques for placing nasoenteric feeding tubes have been developed, which improve placement success and efficiency. It appears that there is an ideal window period of 24-48 h when enteral feeding should be started in critically ill patients. Most patients can be fed into the stomach, but certain groups may benefit from small bowel feeding. Protocols on how to start and monitor enteral feeding have been developed. Immune-modulating feeding formulations also appear to be beneficial in specific patient populations. The gastroenterologist is a crucial member of the multidisciplinary team for nutritional support in the intensive care unit patient, with his knowledge of gastrointestinal pathophysiology, nutrition, and endoscopic feeding-tube placement.

Managing gastric residual volumes in the critically ill patient: an update.

PURPOSE OF REVIEW: Gastric residual volumes (GRVs) remain a major deterrent to adequately feeding patients with gastric-delivered enteral nutrition. The purpose of this review was to define the most up-to-date consensus of the utility of the use of GRVs for monitoring tube-feeding intolerance in gastric-fed patients. RECENT FINDINGS: The paper summarizes the pathophysiology of gastroparesis, the techniques for measuring GRVs, the significance of a large GRV, other factors to consider when measuring GRVs, the correlation between GRVs and aspiration pneumonia, national guideline statements on GRVs, the use of prokinetic agents in the treatment of high GRVs and the clinical impact of tolerating larger GRVs. The utility of GRVs for prevention of aspiration events with tube feeding has been brought into question. SUMMARY: Large GRVs usually result from some impediment in gastrointestinal motility (e.g. gastroparesis). There are numerous methods for measuring GRVs, most of which have not been standardized. It appears that there is little correlation between large GRVs and the development of aspiration pneumonia when tube feeding patients. Prokinetic agents have an inconsistent effect on the GRV size. US guidelines state that GRVs of less than 500 ml should not result in termination of enteral feeding. Allowing larger GRVs will allow patients to receive more calories when gastric fed without a deleterious clinical impact. The use of GRVs as a marker of feeding tolerance is of questionable utility.

Non-alcoholic Steatohepatitis: From Pathophysiology to Clinical Practice.

Non-alcoholic steatohepatitis (NASH) is becoming a global disease with significant associated comorbidities. To date, there are no commercialized drugs to treat NASH, outside of India; however, there is an abundance of new molecular entities which are in clinical development, some in phase III trials. Many of these trials have created an especially heavy demand for USA-based subjects. Hepatologists currently play a major role in the diagnosis, treatment and clinical-trial enrolment of patients with NASH. However, NASH has a strong metabolic component, with patients often carrying comorbid diseases, such as type 2 diabetes mellitus, obesity, hyperlipidaemia, hypothyroidism and sex steroid disorders. The primary care physician, internist and endocrinologist stand at a pivotal position in the NASH healthcare delivery system, as many of the diseases they commonly encounter are associated with a higher risk of developing NASH. Specialty society practice guidelines are evolving regarding the identification and care of patients with NASH. This review of the literature, and assessment of IQVIA's proprietary patient claims database of diagnosis codes, patient encounters and treatments, substantiates the importance of the primary care provider and endocrinologist in the clinical care and clinical research of patients with NASH.

Enteral nutrition in patients with dementia and stroke.

PURPOSE OF REVIEW: Patients suffering from dementia or significant cognitive impairment (SCI) due to neurologic injury routinely receive percutaneous endoscopic gastrostomy (PEG) due to swallowing difficulty or lack of appetite. This review discusses current data and opinion regarding the risks and benefits of PEG in these populations. RECENT FINDINGS: The current data regarding PEG placement in patients with dementia or SCI due to neurologic injury do not confirm either improvement or worsening of survival. Significant risk factors for poor prognosis after PEG include sex, hypoalbuminemia, age, chronic heart failure, and subtotal gastrectomy. Complications associated with enteral nutrition are minor and easily controlled when managed by a nutritional team. Alternative options for feeding elderly demented patients are available for family members considering PEG. SUMMARY: In contrast to previously published data regarding worse clinical outcomes in the dementia and SCI populations receiving PEG, recent data suggest that clinical outcomes in this population are no different than in other patient populations receiving PEG. A prospective, randomized study is needed to ascertain whether PEG is appropriate and beneficial in the dementia/SCI populations.

Screening and therapy for malnutrition and related gastro-intestinal disorders in systemic sclerosis: recommendations of a North American expert panel.

OBJECTIVES: To develop a set of recommendations for clinicians caring for patients with systemic sclerosis (SSc) to guide their approach to the patient with malnutrition and possible malabsorption. METHODS: The Canadian Scleroderma Research Group convened a meeting of experts in the areas of nutrition, speech pathology, oral health in SSc, SSc and gastroenterology to discuss the nutrition-GI paradigm in SSc. This meeting generated a set of recommendations based on expert opinion. RESULTS: Physicians should screen ALL patients with SSc for malnutrition. The physician should ask a series of questions that pertain to GI involvement. Patients who screen positive for malnutrition should be referred to a dietitian and gastroenterologist. Referral to a patient support group should be considered and if screening reveals oral health problems, referral to a dentist, preferably with expertise in treating patients with SSc, should be done. All SSc patients should weigh themselves monthly and report any sudden significant changes in weight. They should be assessed by a rheumatologist once a year for signs of malnutrition. CONCLUSIONS: Malnutrition may be common in SSc and a multidisciplinary approach is important.

Risk factors for gastrointestinal ulcer disease in the US population.

PURPOSE: Gastrointestinal (GI) ulcers are frequently seen in patients with multiple chronic medical conditions. Few studies have described the overall prevalence, comorbidities, or risk factors associated with this diagnosis. We sought to determine among a national dataset if individuals with certain medical comorbidities are at increased risk for gastrointestinal ulcer disease, while controlling for relevant confounders. RESULTS: The overall prevalence of GI ulcer is 8.4%. A significant increased risk of ulcer history is associated with older age (OR 1.67), African-Americans (OR 1.20) current (OR 1.99) and former (OR 1.55) tobacco use, former alcohol use (OR 1.29), obesity (OR 1.18), chronic obstructive pulmonary disease (OR 2.34), chronic renal insufficiency (OR 2.29), coronary heart disease (OR 1.46), and three or more doctor visits in a year (OR 1.49). CONCLUSIONS: This large US population-based study reports on a number of demographic, behavioral, and chronic medical conditions associated with higher risk of gastrointestinal ulcer disease.

Recruitment and Retention of Patients for Nonalcoholic Steatohepatitis Clinical Trials.

The volume of clinical studies globally in nonalcoholic fatty liver disease has created tremendous competition among sponsors and investigators to identify patients. Patients with nonalcoholic steatohepatitis are often asymptomatic and personally unaware and uneducated about the disease. In addition, many physicians caring for undiagnosed patients are also poorly informed of the disease. This has created a perfect storm of high demand for clinical research participants among a pool of difficult to identify patients with nonalcoholic steatohepatitis. Based on the current data, the current volume of nonalcoholic fatty liver disease studies requires 13,049 patients to fulfill their patient enrollment requirements.

Small bowel endoscopic enteral access.

PURPOSE OF REVIEW: Small bowel endoscopic enteral access is perceived as difficult. However, small bowel access is necessary for patients who are unable to tolerate gastric feedings. This review discusses the successes and challenges involved with endoscopic small bowel tube placement in various populations using a variety of placement techniques. RECENT FINDINGS: In general, direct percutaneous endoscopic jejunostomy (DPEJ) is becoming a more common procedure performed to obtain small bowel enteral access. BMI may be a useful predictor of DPEJ tube placement success and complication rates. A retrospective review determined that DPEJ tube placement significantly decreased the incidence of aspiration pneumonia in patients with previous recurrent aspiration pneumonia episodes. DPEJ is an effective method of providing enteral nutrition for patients when percutaneous endoscopic gastrostomy is not indicated because of anatomical or gastric function abnormalities. However, there are known complications of DPEJ, including small bowel volvulus. Nasojejunal tubes also can provide enteral access to the small intestine. Endoscopic insertion of nasojejunal tubes promotes decreased length of hospital stay and early initiation of enteral feedings as compared with bedside self-migrating jejunal tubes in patients with severe acute pancreatitis. Endoscopically placed small bowel feeding tubes can safely deliver enteral nutrition to patients when gastric feedings are not indicated. SUMMARY: Continued evaluation of endoscopic jejunal tube placement methods and associated clinical outcomes in assorted populations is necessary to determine the safest and most effective technique.

Dementia and cognitive impairment are not associated with earlier mortality after percutaneous endoscopic gastrostomy.

BACKGROUND: Studies have shown varying results with regard to risk factors for mortality after percutaneous endoscopic gastrostomy (PEG). OBJECTIVES: To examine the time to death in patients with dementia or significant cognitive impairment (SCI) due to neurologic injury who had undergone PEG compared with patients without either of these diagnoses, and to examine risk factors for 30-day mortality after PEG. METHODS: Patients who had undergone PEG over a 2-year period were identified. Local medical records and the Social Security Death Index were reviewed to ascertain the patients' age, gender, serum albumin, diagnoses, presence or absence of dementia or SCI, presence or absence of complications related to PEG, and length of survival after PEG. The Charlson Comorbidity Index (CCI) was calculated based on the medical diagnoses at the time of PEG. RESULTS: One hundred ninety patients were identified. Forty-five carried a diagnosis of dementia and/or SCI compared with 145 who did not. Median survival of patients with dementia or SCI was 53 days compared with 78 days in patients without these diagnoses (P=.85). Age (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.04-1.12) and albumin (OR 0.43, 95% CI 0.22-0.84) were associated with 30-day mortality, whereas gender (OR 1.2, 95% CI 0.47-2.90), CCI (OR 1.1, 95% CI 0.86-1.32), and presence of PEG-related complications (OR 1.6, 95% CI 0.36-6.76) were not. CONCLUSIONS: Age and serum albumin are risk factors for 30-day mortality after PEG. Patients with dementia or SCI do not have a significantly shorter survival after PEG than patients with intact cognitive function.

Comparison of resting energy expenditure prediction methods with measured resting energy expenditure in obese, hospitalized adults.

BACKGROUND: Several methods are available to estimate caloric needs in hospitalized, obese patients who require specialized nutrition support; however, it is unclear which of these strategies most accurately approximates the caloric needs of this patient population. The purpose of this study was to determine which strategy most accurately predicts resting energy expenditure in this subset of patients. METHODS: Patients assessed at high nutrition risk who required specialized nutrition support and met inclusion and exclusion criteria were enrolled in this observational study. Adult patients were included if they were admitted to a medical or surgical service with a body mass index > or = 30 kg/m(2). Criteria excluding patient enrollment were pregnancy and intolerance or contraindication to indirect calorimetry procedures. Investigators calculated estimations of resting energy expenditure for each patient using variations on the following equations: Harris-Benedict, Mifflin-St. Jeor, Ireton-Jones, 21 kcal/kg body weight, and 25 kcal/kg body weight. For nonventilated patients, the MedGem handheld indirect calorimeter was used. For ventilated patients, the metabolic cart was used. The primary endpoint was to identify which estimation strategy calculated energy expenditures to within 10% of measured energy expenditures. RESULTS: The Harris-Benedict equation, using adjusted body weight with a stress factor, most frequently estimated resting energy expenditure to within 10% measured resting energy expenditure at 50% of patients. CONCLUSION: Measured energy expenditure with indirect calorimetry should be employed when developing nutrition support regimens in obese, hospitalized patients, as estimation strategies are inconsistent and lead to inaccurate predictions of energy expenditure in this patient population.

Tube feeding in patients with dementia: where are we?

Dementia is a common diagnosis and accounts for significant morbidity and mortality. In the United States, the practice of medicine commonly dictated that dementia patients with dysphagia should receive a feeding tube. A review of the evidence in 1999 was completed to understand the validity of the premise of an improvement in a dementia patient's survival, quality of life, malnutrition, and comorbid diseases with tube feeding. The available literature reviewed was sparse. The retrospective and prospective observational studies noted no improvement in the above-mentioned outcomes in dementia patients with the use of tube feeding. Interestingly, a recent retrospective review denoted that dementia patients had no worse survival than patients with other diseases receiving a feeding tube and tube feedings. A prospective study comparing tube feeding to hand feeding in the dementia population is sorely needed.

The impact of fiber supplementation on ADMA levels.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an emerging biomarker that has been associated with oxidative metabolism and increased cardiovascular risk. Little information is available regarding the effect of diet on ADMA. METHODS: The authors studied 86 overweight/obese adults as part of a clinical trial of psyllium supplementation to determine whether 3 months of such supplementation would affect ADMA levels. Forty-one people in the intervention group received 14 g/day of psyllium in addition to their usual diet compared with 45 controls who followed their usual diet alone. The 2 groups were comparable at baseline in demographic characteristics and body mass index. RESULTS: Baseline ADMA levels were elevated in this overweight/obese population compared with published reference values in healthy individuals (0.75 vs 0.50 micromol/L). The change in ADMA levels over 3 months was not different in the psyllium group compared with the control group (-.03 vs -.01 micromol/L, P=.73). CONCLUSIONS: These findings do not support a significant effect of psyllium fiber supplementation on ADMA.

Percutaneous endoscopic gastrostomy in the dementia patient: helpful or hindering?

Percutaneous endoscopic gastrostomy (PEG) is a common technique performed worldwide. Recently, the use of PEG in the dementia patient with dysphagia for nutrition support has been called into question. Some reviews have reported no improvement in survival with PEG tubes in this population. Higaki and colleagues now present a large review of PEG tube placement in patients with dementia, which demonstrates a similar survival rate in patients without dementia receiving PEG tubes. The question of the utility of PEG tube placement for nutrition support in the dementia population requires an organized, prospective analysis to concretely answer the question.

The impact of race on weight loss after Roux-en-Y gastric bypass surgery.

BACKGROUND: Gastric bypass surgery for morbid obesity has dramatically increased in volume over the past decade. Caucasian patients have been noted previously to lose more weight after bariatric surgery than African-Americans patients. Data regarding predictors of maintaining weight loss after surgery are minimal. We sought to determine predictors of long-term weight loss after bariatric surgery. METHODS: Retrospective analysis using a multivariate logistic regression model of all patients undergoing Roux-en-Y gastric bypass surgery at the Medical University of South Carolina from May 1993 to December 2004 for whom 2 years of follow-up data was available. Our dependent variable was the percentage of weight lost from baseline, dichotomized at +/-35%. Our primary independent variable was race, defined as Caucasian, African-American, or other. Relevant covariates were added to the model to control for their potential effects on outcome. RESULTS: One hundred eleven patients (17 male/94 female; 85% Caucasian, mean age 44 years (range 18-68 years). In our model, Caucasian subjects (adjusted odds ratio [OR] = 7.60, 95% confidence intervals [95%CI] = 1.83-31.5) and late post surgical complications (adjusted OR = 2.67, 95%CI = 1.05-6.80) significantly predicted weight loss at 2 years, after controlling for relevant confounders. Other covariates did not significantly impact the model. CONCLUSION: Race and late post surgical complications significantly impacted the percentage of weight loss at 2 years for patients undergoing Roux-en-Y gastric bypass surgery at our institution. Future research should be directed at determining potential genetic and/or social reasons for these differences.

Enteral feeding.

PURPOSE OF REVIEW: Enteral nutrition is a widely used therapy for nutritional treatment of patients with multiple pathologies. The present review selects important evidenced-based papers from 2006 and 2007 and critically reviews them for the reader. RECENT FINDINGS: Use of synbiotics and probiotics is gaining acceptance. Supplements such as glutamine may be important for wound healing. Enteral feeding in malnourished patients may result in rapid growth of gut mucosal protein. Antibiotics are important for reduction of postpercutaneous endoscopic gastrostomy infections. Early enteral nutrition in burn patients blunts the hypermetabolic response. Polymeric enteral formulations in vitro have a direct anti-inflammatory effect on enterocytes. Enteral nutrition, however, does not appear better than steroid use for induction of remission in Crohn's disease. Long-term (12-week) infusion of immune-enhancing enteral formulas in a nonsurgical patient group is well tolerated and safe. Finally, large reviews of enteral nutrition and their efficacy for specific disease states continue to demonstrate the difficulty in interpreting multiple small clinical studies. SUMMARY: Enteral nutrition continues as a highly used medical therapy, usually as an adjuvant for other pharmacologic and supportive therapies. Multiple small clinical trials, observational studies and retrospective reviews must be analyzed to develop 'best practice' guidelines with enteral nutrition.