Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant.

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."

Expert consensus report on lipid mediators: Role in resolution of inflammation and muscle preservation.

This meeting report presents a consensus on the biological aspects of lipid emulsions in parenteral nutrition, emphasizing the unanimous support for the integration of lipid emulsions, particularly those containing fish oil, owing to their many potential benefits beyond caloric provision. Lipid emulsions have evolved from simple energy sources to complex formulations designed to improve safety profiles and offer therapeutic benefits. The consensus highlights the critical role of omega-3 polyunsaturated fatty acids (PUFAs), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil and other marine oils, for their anti-inflammatory properties, muscle mass preservation, and as precursors to the specialized pro-resolving mediators (SPMs). SPMs play a significant role in immune modulation, tissue repair, and the active resolution of inflammation without impairing host defense mechanisms. The panel's agreement underscores the importance of incorporating fish oil within clinical practices to facilitate recovery in conditions like surgery, critical illness, or immobility, while cautioning against therapies that might disrupt natural inflammation resolution processes. This consensus not only reaffirms the role of specific lipid components in enhancing patient outcomes, but also suggests a shift towards nutrition-based therapeutic strategies in clinical settings, advocating for the proactive evidence-based use of lipid emulsions enriched with omega-3 PUFAs. Furthermore, we should seek to apply our knowledge concerning DHA, EPA, and their SPM derivatives, to produce more informative randomized controlled trial protocols, thus allowing more authoritative clinical recommendations.

Combining proteins with n-3 PUFAs (EPA + DHA) and their inflammation pro-resolution mediators for preservation of skeletal muscle mass.

The optimal feeding strategy for critically ill patients is still debated, but feeding must be adapted to individual patient needs. Critically ill patients are at risk of muscle catabolism, leading to loss of muscle mass and its consequent clinical impacts. Timing of introduction of feeding and protein targets have been explored in recent trials. These suggest that "moderate" protein provision (maximum 1.2 g/kg/day) is best during the initial stages of illness. Unresolved inflammation may be a key factor in driving muscle catabolism. The omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are substrates for synthesis of mediators termed specialized pro-resolving mediators or SPMs that actively resolve inflammation. There is evidence from other settings that high-dose oral EPA + DHA increases muscle protein synthesis, decreases muscle protein breakdown, and maintains muscle mass. SPMs may be responsible for some of these effects, especially upon muscle protein breakdown. Given these findings, provision of EPA and DHA as part of medical nutritional therapy in critically ill patients at risk of loss of muscle mass seems to be a strategy to prevent the persistence of inflammation and the related anabolic resistance and muscle loss.

Persistent Ostomy Following Percutaneous Endoscopic Gastrostomy Removal: Treatment Strategies.

PURPOSE OF REVIEW: The purpose of this article is to review available literature on management of persistent ostomy following PEG tube removal. We will discuss the incidence of persistent gastrocutaneous fistula (GCF) following PEG tube removal, risk factors for their development, and management strategies that have been proposed and their efficacy. RECENT FINDINGS: The use of over the scope clips (OTSC) have evolved recently in the management of gastrointestinal bleeding, perforation, and fistula closures. OTSC has become more readily available and proven to be effective and safe. Suturing devices have shown promising results. Persistent gastrocutaneous fistula following PEG removal is a rare yet serious complication that can lead to continuous skin irritation and leakage of gastric contents and acid. There are several postulated risk factors but the most important of these is duration of placement. Management can include medical therapy which has recently been shown to be somewhat effective, endoscopic therapy and surgery as a last resort. Overall, the data on GCFs is limited and further study with larger sample size is needed.

Colonic Microbial Abundances Predict Adenoma Formers.

OBJECTIVE: We aimed to examine associations between the oral, fecal, and mucosal microbiome communities and adenoma formation. SUMMARY BACKGROUND DATA: Data are limited regarding the relationships between microbiota and preneoplastic colorectal lesions. METHODS: Individuals undergoing screening colonoscopy were prospectively enrolled and divided into adenoma and nonadenoma formers. Oral, fecal, nonadenoma and adenoma-adjacent mucosa were collected along with clinical and dietary information. 16S rRNA gene libraries were generated using V4 primers. DADA2 processed sequence reads and custom R-scripts quantified microbial diversity. Linear regression identified differential taxonomy and diversity in microbial communities and machine learning identified adenoma former microbial signatures. RESULTS: One hundred four subjects were included, 46% with adenomas. Mucosal and fecal samples were dominated by Firmicutes and Bacteroidetes whereas Firmicutes and Proteobacteria were most abundant in oral communities. Mucosal communities harbored significant microbial diversity that was not observed in fecal or oral communities. Random forest classifiers predicted adenoma formation using fecal, oral, and mucosal amplicon sequence variant (ASV) abundances. The mucosal classifier reliably diagnosed adenoma formation with an area under the curve (AUC) = 0.993 and an out-of-bag (OOB) error of 3.2%. Mucosal classifier accuracy was strongly influenced by five taxa associated with the family Lachnospiraceae, genera Bacteroides and Marvinbryantia, and Blautia obeum. In contrast, classifiers built using fecal and oral samples manifested high OOB error rates (47.3% and 51.1%, respectively) and poor diagnostic abilities (fecal and oral AUC = 0.53). CONCLUSION: Normal mucosa microbial abundances of adenoma formers manifest unique patterns of microbial diversity that may be predictive of adenoma formation.

New features of parenteral nutrition in home care and acute care setting for the older population.

PURPOSE OF REVIEW: The intent of this review is to highlight any recent changes in the delivery of parenteral nutrition to the geriatric population. The percentage of patients in the geriatric age group increases clinical awareness of the potential risks and benefits of appropriate parenteral nutrition delivery, which is crucial to well tolerated and optimum outcomes. RECENT FINDINGS: The major recent finding is the increased awareness of risk of parenteral nutrition in the elderly population. SUMMARY: The implications of this very brief review expose the need for further focused studies to better clarify the specifics of parenteral nutrition in this vulnerable ageing population. The importance of nutritional risk assessment cannot be overstated. With the rapidly expanding volume of geriatric population, the need for more data to better understand the delicate balance in parenteral nutrition therapy for both the acute care setting and home parenteral population is needed.

Gut Microbiome and Its Impact on Obesity and Obesity-Related Disorders.

PURPOSE OF REVIEW: The prevalence of overweight and obesity has been increasing worldwide at an alarming rate. Gut microbiota intimately influence host energy metabolism, and immune response. Studies indicate a prominent role of gut dysbiosis in propagating inflammation that is associated with the development of obesity and obesity-related disorders such as type 2 diabetes mellitus, metabolic syndrome, and non-alcoholic fatty liver disease. This article will review the current literature on gut microbiome and its impact on obesity and obesity-related disorders. RECENT FINDINGS: An altered gut microbial composition in obesity and obesity-related disorders is associated with enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability, increased production of proinflammatory metabolites, such as lipopolysaccharides, resulting in systemic inflammation and insulin resistance. Gut microbiota modulation can be achieved either by dietary manipulation or by administration of probiotics, prebiotics, synbiotics, and/or fecal microbiota transplantation aiming at the improvement of the gut dysbiosis in obesity and metabolic disorders. Further clinical trials are required to better elucidate the dose, and frequency of these interventions and also their long-term impact on host metabolism.

All Fiber is Not Fiber.

PURPOSE OF REVIEW: Epidemiologic studies and clinical trials have demonstrated the benefits of dietary fiber. This occurs through a combination of the physiochemical properties of fiber and through microbial fermentation that occurs in the colon which result in the production of short-chain fatty acids (SCFA). The purpose of this review is to highlight the physiochemical properties of fiber that result in the range of physiologic effects and to review the literature on the health benefits of acetate, propionate, and butyrate. RECENT FINDINGS: Of the variety of properties and functions exerted by dietary fibers, the fermentability and production of SCFA's are emphasized in this review. Studies done in both animal and humans reveal the anti-obesity, anti-inflammatory, and possible anti-neoplastic roles SCFAs exert at the mucosal level. Many clinical questions remain regarding the optimal dose, type, and method of delivery of fiber to exert the desired beneficial effects. It has the potential to be used in the management of clinical symptoms, prevention of disease, and improvement in human health. Further studies to address this novel use of fiber has the potential to make a large impact in clinical practice.

Identification of SARS-CoV-2 RNA in healthcare heating, ventilation, and air conditioning units.

Evidence continues to grow supporting the aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the potential role of heating, ventilation, and air conditioning (HVAC) systems in airborne viral transmission, this study sought to determine the viral presence, if any, on air handling units in a healthcare setting where coronavirus disease 2019 (COVID-19) patients were being treated. The presence of SARS-CoV-2 RNA was detected in approximately 25% of samples taken from ten different locations in multiple air handlers. While samples were not evaluated for viral infectivity, the presence of viral RNA in air handlers raises the possibility that viral particles can enter and travel within the air handling system of a hospital, from room return air through high-efficiency MERV-15 filters and into supply air ducts. Although no known transmission events were determined to be associated with these specimens, the findings suggest the potential for HVAC systems to facilitate transfer of virions to locations remote from areas where infected persons reside. These results are important within and outside of healthcare settings and may present necessary guidance for building operators of facilities that are not equipped with high-efficiency filtration. Furthermore, the identification of SARS-CoV-2 in HVAC components indicates the potential utility as an indoor environmental surveillance location.

Gastrointestinal Dysfunction and Feeding Intolerance in Critical Illness: Do We Need an Objective Scoring System?

PURPOSE OF REVIEW: Efforts to provide early enteral nutrition in critical illness are thwarted by gastrointestinal dysfunction and feeding intolerance. While many of the signs and symptoms of this dysfunction reflect gastroparesis and intestinal dysmotility, other symptoms which may or may not be related are often included such as diarrhea, bleeding, and intra-abdominal hypertension. This paper discusses the need to monitor tolerance of nutritional therapy in the critical care setting and reviews the results of those clinical trials which have helped establish objective measures, define feeding intolerance, and provide a tool to guide continued delivery of the enteral regimen. RECENT FINDINGS: While definitions vary, the presence of gastrointestinal dysfunction and feeding intolerance correlates with adverse clinical outcomes, including prolonged duration of mechanical ventilation, greater length of stay in the intensive care unit, and increased mortality. Despite their prognostic value, it is not clear to what extent these scoring systems should direct nutritional therapy. The clinician should be astute in the careful selection of monitors, in identifying and addressing signs and symptoms of intolerance, and by responding appropriately with feeding strategies that are effective and safe. Early enteral feeding in critical illness has been shown to be optimized by following protocols which allow monitoring patient tolerance while providing individualized care.

Appendiceal cancer masked as inflammatory appendicitis in the elderly, not an uncommon presentation (Surveillance Epidemiology and End Results (SEER)-Medicare Analysis).

BACKGROUND: The misdiagnosis of appendiceal cancer as inflammatory appendicitis is becoming of greater clinical concern because of the rise of nonoperative management especially in the elder population. To quantify this rate of misdiagnosis, we retrospectively reviewed SEER-Medicare data. METHODS: The SEER-Medicare database was reviewed from 2000 to 2014. We identified patients older than 65 years old who were diagnosed with appendiceal cancer and then cross-referenced them for a diagnosis of inflammatory appendicitis. Demographic data and oncologic stage were collected. RESULTS: Our results showed that 28.6% of appendiceal cancer patients received an incorrect initial diagnosis of inflammatory appendicitis. Patients older than 75 years of age were more likely to be misdiagnosed than those between ages 65 and 75 (risk ratio [RR]: 0.81; 95% confidence interval: 0.70-0.93; P = .003). We found that 42% of patients within the misdiagnosis group presented with an earlier stage of disease (stage 1 or 2) compared to 26% of those primarily diagnosed with appendiceal cancer (P < .001). CONCLUSION: A significant proportion of patients older than 65 years old with appendiceal cancer were initially misdiagnosed with acute appendicitis. We suggest caution when considering a nonoperative approach for appendicitis in the elderly and follow-up imaging or an interval appendectomy should be part of the treatment plan.

Travel distance influences readmissions in colorectal cancer patients-what the primary operative team needs to know.

BACKGROUND: Many colorectal cancer patients receive complex surgical care remotely. We hypothesized that their readmission rates would be adversely affected after accounting for differences in travel distance from primary/index hospital and correlate with mortality. MATERIALS AND METHODS: We identified 48,481 colorectal cancer patients in the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Travel distance was calculated, using Google Maps, and SAS. Multivariate negative binomial regression was used to identify factors associated with readmission rates. Overall survival was analyzed, using Kaplan-Meier and Cox proportional hazard. RESULTS AND CONCLUSIONS: Thirty-day readmissions occurred in 14.9% of the cohort, 27.5% of which were to a nonindex hospital. In the colon and rectal cancer cohorts, readmissions were 14.5% and 16.5%, respectively. Rectal cancer patients had an increase in readmission by 13% (incidence rate ratios [IRR] 1.13; 95% confidence interval [CI] 1.05-1.21). Factors associated with readmission were male gender, advanced disease, length of stay (LOS), discharge disposition, hospital volume, Charlson score, and poverty level (P < 0.05). Greater distance traveled increased the likelihood of readmission but did not affect mortality. Travel distance influences readmission rates but not mortality. Discharge readiness to decrease readmissions is essential for colorectal cancer patients discharged from index hospitals.

Can Specialized Pro-resolving Mediators Deliver Benefit Originally Expected from Fish Oil?

PURPOSE OF THE REVIEW: Fish oil (FO) supplementation has historically been used by individuals suffering from cardiovascular disease and other inflammatory processes. However, a meta-analysis of several large randomized control trials (RCTs) suggested FO conferred no benefit in reducing cardiovascular risk. Skeptics surmised that the lack of benefit was related to FO dose or drug interactions; therefore, the widely accepted practice of FO consumption was brought into question. RECENT FINDINGS: Thereafter, Serhan et al. identified specialized pro-resolving mediators (SPMs) to be one of the bioactive components and mechanisms of action of FO. SPMs are thought to enhance resolution of inflammation, as opposed to classic anti-inflammatory agents which inhibit inflammatory pathways. Numerous diseases, including persistent Inflammation, immunosuppression, and catabolic syndrome (PICS), are rooted in a burden of chronic inflammation. SPMs are gaining traction as potential therapeutic agents used to resolve inflammation in cardiovascular disorders, inflammatory bowel disease, sepsis, pancreatitis, and acute respiratory distress syndrome (ARDS). This narrative reviews the history of FO and the various studies that made the health benefits of FO inconclusive, as well as an overview of SPMs and their use in specific disease states.

Prospective evaluation of poly-4-hydroxybutyrate mesh in CDC class I/high-risk ventral and incisional hernia repair: 18-month follow-up.

BACKGROUND: Long-term resorbable mesh represents a promising technology for complex ventral and incisional hernia repair (VIHR). Preclinical studies indicate that poly-4-hydroxybutyrate (P4HB) resorbable mesh supports strength restoration of the abdominal wall. This study evaluated outcomes of high-risk subjects undergoing VIHR with P4HB mesh. METHODS: This was a prospective, multi-institutional study of subjects undergoing retrorectus or onlay VIHR. Inclusion criteria were CDC Class I, defect 10-350 cm2, ≤ 3 prior repairs, and ≥ 1 high-risk criteria (obesity (BMI: 30-40 kg/m2), active smoker, COPD, diabetes, immunosuppression, coronary artery disease, chronic corticosteroid use, hypoalbuminemia, advanced age, and renal insufficiency). Physical exam and/or quality of life surveys were performed at regular intervals through 18 months (to date) with longer-term, 36-month follow-up ongoing. RESULTS: One hundred and twenty-one subjects (46M, 75F) with an age of 54.7 ± 12.0 years and BMI of 32.2 ± 4.5 kg/m2 (mean ± SD), underwent VIHR. Comorbidities included the following: obesity (n = 95, 78.5%), hypertension (n = 72, 59.5%), cardiovascular disease (n = 42, 34.7%), diabetes (n = 40, 33.1%), COPD (n = 34, 28.1%), malignancy (n = 30, 24.8%), active smoker (n = 28, 23.1%), immunosuppression (n = 10, 8.3%), chronic corticosteroid use (n = 6, 5.0%), advanced age (n = 6, 5.0%), hypoalbuminemia (n = 3, 2.5%), and renal insufficiency (n = 1, 0.8%). Hernia types included the following: primary ventral (n = 17, 14%), primary incisional (n = 54, 45%), recurrent ventral (n = 15, 12%), and recurrent incisional hernia (n = 35, 29%). Defect and mesh size were 115.7 ± 80.6 and 580.9 ± 216.1 cm2 (mean ± SD), respectively. Repair types included the following: retrorectus (n = 43, 36%), retrorectus with additional myofascial release (n = 45, 37%), onlay (n = 24, 20%), and onlay with additional myofascial release (n = 8, 7%). 95 (79%) subjects completed 18-month follow-up to date. Postoperative wound infection, seroma requiring intervention, and hernia recurrence occurred in 11 (9%), 7 (6%), and 11 (9%) subjects, respectively. CONCLUSIONS: High-risk VIHR with P4HB mesh demonstrated positive outcomes and low incidence of hernia recurrence at 18 months. Longer-term 36-month follow-up is ongoing.

Understanding and Resetting Radiation Sensitivity in Rectal Cancer.

OBJECTIVE: The aim of the study was to explore specific microRNAs (miRs) in rectal cancer that would predict response to radiation and identify target pathways that may be exploited for neoadjuvant therapies. SUMMARY BACKGROUND DATA: Chemoradiotherapy (CRT) response is a predictor of survival in rectal cancer. Studies have demonstrated changes in RNA expression correlate with chemoradiation sensitivity across cancers. METHODS: Forty-five rectal cancer patients, partial responders (PR = 18), nonresponders (NR = 13), and complete responders (CR = 14) to CRT, as defined by a tumor regression score, were examined. miRs differentially expressed, using NanoString microArray profiling, were validated with qPCR. We quantified 1 miR and its downstream targets in patient samples. Chemosensitivity was measured in HCT-116, a human colorectal carcinoma cell line, using inhibitors of SHP2 and RAF. RESULTS: miR-451a, 502-5p, 223-3p, and 1246 were the most upregulated miRs (>1.5-fold change) in a NanoString profiling miR panel. qPCR revealed a decrease in expression of miR-451a in NRs. EMSY and CAB39, both downstream targets of miR-451a and involved in carcinogenesis (shown in TCGA) were increased in NRs (qPCR). Both targets are associated with worse survival in colorectal cancer. Inhibition of miR-451a in HCT-116 cells significantly decreased cell proliferation with treatment of SHP2 and RAF inhibitors. CONCLUSIONS: An integrated analysis of rectal cancer miRs may yield biomarkers of radioresistance and offer treatment targets for resensitization.

Ventral Hernia Management: Expert Consensus Guided by Systematic Review.

OBJECTIVE: To achieve consensus on the best practices in the management of ventral hernias (VH). BACKGROUND: Management patterns for VH are heterogeneous, often with little supporting evidence or correlation with existing evidence. METHODS: A systematic review identified the highest level of evidence available for each topic. A panel of expert hernia-surgeons was assembled. Email questionnaires, evidence review, panel discussion, and iterative voting was performed. Consensus was when all experts agreed on a management strategy. RESULTS: Experts agreed that complications with VH repair (VHR) increase in obese patients (grade A), current smokers (grade A), and patients with glycosylated hemoglobin (HbA1C) ≥ 6.5% (grade B). Elective VHR was not recommended for patients with BMI ≥ 50 kg/m (grade C), current smokers (grade A), or patients with HbA1C ≥ 8.0% (grade B). Patients with BMI= 30-50 kg/m or HbA1C = 6.5-8.0% require individualized interventions to reduce surgical risk (grade C, grade B). Nonoperative management was considered to have a low-risk of short-term morbidity (grade C). Mesh reinforcement was recommended for repair of hernias ≥ 2 cm (grade A). There were several areas where high-quality data were limited, and no consensus could be reached, including mesh type, component separation technique, and management of complex patients. CONCLUSIONS: Although there was consensus, supported by grade A-C evidence, on patient selection, the safety of short-term nonoperative management, and mesh reinforcement, among experts; there was limited evidence and broad variability in practice patterns in all other areas of practice. The lack of strong evidence and expert consensus on these topics has identified gaps in knowledge where there is need of further evidence.

ACG Clinical Guideline: Nutrition Therapy in the Adult Hospitalized Patient.

The value of nutrition therapy for the adult hospitalized patient is derived from the outcome benefits achieved by the delivery of early enteral feeding. Nutritional assessment should identify those patients at high nutritional risk, determined by both disease severity and nutritional status. For such patients if they are unable to maintain volitional intake, enteral access should be attained and enteral nutrition (EN) initiated within 24-48 h of admission. Orogastric or nasogastric feeding is most appropriate when starting EN, switching to post-pyloric or deep jejunal feeding only in those patients who are intolerant of gastric feeds or at high risk for aspiration. Percutaneous access should be used for those patients anticipated to require EN for >4 weeks. Patients receiving EN should be monitored for risk of aspiration, tolerance, and adequacy of feeding (determined by percent of goal calories and protein delivered). Intentional permissive underfeeding (and even trophic feeding) is appropriate temporarily for certain subsets of hospitalized patients. Although a standard polymeric formula should be used routinely in most patients, an immune-modulating formula (with arginine and fish oil) should be reserved for patients who have had major surgery in a surgical ICU setting. Adequacy of nutrition therapy is enhanced by establishing nurse-driven enteral feeding protocols, increasing delivery by volume-based or top-down feeding strategies, minimizing interruptions, and eliminating the practice of gastric residual volumes. Parenteral nutrition should be used in patients at high nutritional risk when EN is not feasible or after the first week of hospitalization if EN is not sufficient. Because of their knowledge base and skill set, the gastroenterologist endoscopist is an asset to the Nutrition Support Team and should participate in providing optimal nutrition therapy to the hospitalized adult patient.

Does the use of specialized proresolving molecules in critical care offer a more focused approach to controlling inflammation than that of fish oils?

PURPOSE OF REVIEW: The literature regarding the use of fish oils in the critically ill to limit the inflammatory and catabolic response have been inconsistent. The objective of this manuscript is to review a newly discovered class of specialized proresolving molecules (SPMs), which could help elucidate the discrepancies reported in the critical care literature regarding the anti-inflammatory benefits of fish oil/ω-3 fatty acids. RECENT FINDINGS: Although use of fish oil has traditionally been thought to reduce or limit the inflammatory process in the critical ill, a new class of endogenously produced highly active lipid mediators derived from arachidonic acid and ω-3 fatty acids (lipoxins, resolvins, protectins, and maresins) have been shown to actively enhance resolution of inflammation. These SPMs stimulate the cardinal signs of resolution of inflammation, which include the cessation of leukocytic infiltration, a countering of the effects of proinflammatory mediators, stimulation of the uptake of apoptotic neutrophils, promotion of the clearance of necrotic cellular debris, and enhancement of the host's ability to eliminate microbial invasion. SUMMARY: By actively turning off inflammation (instead of simply attenuating its natural course), SPMs have shown more consistent effects in decreasing pain and risk of sepsis, increasing epithelialization and wound healing, promoting tissue regeneration, potentiating the effects of antibiotics, and enhancing adaptive immunity.

Parenteral or Enteral Arginine Supplementation Safety and Efficacy.

Arginine supplementation has the potential to improve the health of patients. Its use in hospitalized patients has been a controversial topic in the nutrition literature, especially concerning supplementation of septic patients. In this article, we review the relevant literature both for and against the use of arginine in critically ill, surgical, and hospitalized patients. The effect of critical illness on arginine metabolism is reviewed, as is its use in septic and critically ill patients. Although mounting evidence supports immunonutrition, there are only a few studies that suggest that this is safe in patients with severe sepsis. The use of arginine has been shown to benefit a variety of critically ill patients. It should be considered for inclusion in combinations of immunonutrients or commercial formulations for groups in whom its benefit has been reported consistently, such as those who have suffered trauma and those in acute surgical settings. The aims of this review are to discuss the role of arginine in health, the controversy surrounding arginine supplementation of septic patients, and the use of arginine in critically ill patients.

Analysis of model development strategies: predicting ventral hernia recurrence.

BACKGROUND: There have been many attempts to identify variables associated with ventral hernia recurrence; however, it is unclear which statistical modeling approach results in models with greatest internal and external validity. We aim to assess the predictive accuracy of models developed using five common variable selection strategies to determine variables associated with hernia recurrence. METHODS: Two multicenter ventral hernia databases were used. Database 1 was randomly split into "development" and "internal validation" cohorts. Database 2 was designated "external validation". The dependent variable for model development was hernia recurrence. Five variable selection strategies were used: (1) "clinical"-variables considered clinically relevant, (2) "selective stepwise"-all variables with a P value <0.20 were assessed in a step-backward model, (3) "liberal stepwise"-all variables were included and step-backward regression was performed, (4) "restrictive internal resampling," and (5) "liberal internal resampling." Variables were included with P < 0.05 for the Restrictive model and P < 0.10 for the Liberal model. A time-to-event analysis using Cox regression was performed using these strategies. The predictive accuracy of the developed models was tested on the internal and external validation cohorts using Harrell's C-statistic where C > 0.70 was considered "reasonable". RESULTS: The recurrence rate was 32.9% (n = 173/526; median/range follow-up, 20/1-58 mo) for the development cohort, 36.0% (n = 95/264, median/range follow-up 20/1-61 mo) for the internal validation cohort, and 12.7% (n = 155/1224, median/range follow-up 9/1-50 mo) for the external validation cohort. Internal validation demonstrated reasonable predictive accuracy (C-statistics = 0.772, 0.760, 0.767, 0.757, 0.763), while on external validation, predictive accuracy dipped precipitously (C-statistic = 0.561, 0.557, 0.562, 0.553, 0.560). CONCLUSIONS: Predictive accuracy was equally adequate on internal validation among models; however, on external validation, all five models failed to demonstrate utility. Future studies should report multiple variable selection techniques and demonstrate predictive accuracy on external data sets for model validation.