Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase.

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.

Preoperative optimization of the radical cystectomy patient: Current state and future directions.

Radical cystectomy (RC) is associated with high rates of morbidity and mortality despite adoption of robotics and implementation of enhanced recovery after surgery protocols. There have been increased efforts to investigate preoperative optimization through comprehensive nutritional evaluation, preoperative supplementation, and prehabilitation outside of previously described enhanced recovery after surgery protocols to reduce mortality and morbidity from RC. In this review, we summarize and evaluate the current literature on preoperative assessment and optimization in RC.

Effect of preoperative immunonutrition on postoperative short-term clinical outcomes in patients with gastric cancer cachexia: a prospective randomized controlled trial.

BACKGROUND: Although current guidelines(ESPEN guideline: Clinical nutrition in surgery and other guidelines) recommend preoperative immunonutrition for cachectic gastric cancer patients, the strength of the recommendation is weak, and the level of evidence is low. The benefits of preoperative immunonutrition still remain controversial. PATIENTS AND METHODS: 112 patients with gastric cancer cachexia were enrolled in the study and randomly assigned in a 1:1 ratio to receive either preoperative enteral immunonutrition support (IN, n = 56) or standard enteral nutrition support (SEN, n = 56). The primary endpoint was the incidence of infectious complications, and the secondary endpoints included the nutritional indicators, inflammatory markers, immune parameters, postoperative recovery and complications and gastrointestinal intolerance reactions. RESULTS: The incidence of postoperative infectious complications(P = 0.040) and overall complications (P = 0.049)was significantly lower in the IN group compared to the SEN group. In terms of laboratory inflammatory indexes, patients in the IN group demonstrated significantly lower levels of white blood cells (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6), as well as higher levels of lymphocytes (LYMPH) and immunoglobulin A (IgA), compared to patients in the SEN group, with statistically significant differences. In terms of clinical outcomes, the IN group had a shorter duration of antibiotic use (P = 0.048), shorter hospital stay (P = 0.018), and lower total hospital costs (P = 0.034) compared to the SEN group. The IN group also experienced significantly less weight loss after surgery (P = 0.043). CONCLUSION: Preoperative administration of immunonutrition formula has a positive impact on the incidence of infectious complications in patients with gastric cancer cachexia after surgery. It improves patients' inflammatory and immune status, shortens hospital stays, and reduces healthcare costs. Preoperative use of immunonutrition may contribute to the improvement of prognosis in this high-risk population.

Nutritional interventions as modulators of the disease activity for idiopathic inflammatory myopathies: a scoping review.

Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune connective tissue diseases associated with significant morbidity and disability. Nutrients can activate the immune system and contribute to chronic low-grade inflammation (LGI). Chronic muscle inflammation leads to imbalanced pro-inflammatory and anti-inflammatory cytokines, causing inadequate nutrition, weight loss and muscle weakness during a negative cycle. Owing to its potential to modulate LGI in various diseases, the Mediterranean diet (Med Diet) has been extensively studied. This scoping review explores the nutritional implications and recommendations of the Med Diet as a treatment for immune-mediated diseases, focusing on the gaps in IIM nutritional interventions. A comprehensive literature search of the MEDLINE and EBSCO databases between September 2018 and December 2022 was performed. We identified that the Med Diet and its specific components, such as omega-3 (nω3) fatty acids, vitamin D and antioxidants, play a role in the dietary treatment of connective tissue-related autoimmune diseases. Nutritional interventions have demonstrated potential for modulating disease activity and warrant further exploration of IIMs through experimental studies. This review introduces a dietary therapeutic approach using the Med Diet and related compounds to regulate chronic inflammatory processes in IIMs. However, further clinical studies are required to evaluate the efficacy of the Med Diet in patients with IIMs. Emphasising a clinical-nutritional approach, this study encourages future research on the anti-inflammatory effects of the Med Diet on IIMs. This review highlights potential insights for managing and treating these conditions using a holistic approach.

Prognostic value of perioperative changes in the prognostic nutritional index in patients with surgically resected non-small cell lung cancer.

PURPOSE: This single-institution retrospective cohort study was conducted to assess the prognostic significance of perioperative changes in the prognostic nutritional index (PNI) in patients who underwent surgery for non-small cell lung cancer (NSCLC). METHODS: Clinicopathological data were collected from 441 patients who underwent lobectomy for NSCLC between 2010 and 2016.The PNI ratio (postoperative PNI/preoperative PNI) was used as an indicator of perioperative PNI changes. Prognostic differences were investigated based on PNI ratios. RESULTS: The optimal cut-off value of the PNI ratio for overall survival (OS) was set at 0.88 using a receiver operating characteristic curve. The PNI ratio was inversely related to a high smoking index, interstitial lung disease, and postoperative pulmonary complications. The 5-year OS rates for the high vs. low PNI ratio groups were 88.2% vs. 68.5%, respectively (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.90-4.86). Multivariable analysis revealed that a low PNI ratio was significantly associated with poor prognosis (HR: 2.94, 95% CI: 1.77-4.87). The PNI ratio was a more sensitive indicator than postoperative PNI status alone for identifying patients at high risk of mortality, particularly those with non-lung cancer causes. CONCLUSION: The perioperative PNI change is a significant prognostic factor for patients with NSCLC.

The Effect of immunonutrition in patients undergoing pancreaticoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex and traumatic abdominal surgery with a high risk of postoperative complications. Nutritional support, including immunonutrition (IMN) with added glutamine, arginine, and ω-3 polyunsaturated fatty acids, can improve patients' prognosis by regulating postoperative inflammatory response. However, the effects of IMN on PD patients' outcomes require further investigation. METHODS: PMC, EMbase, web of science databases were used to search literatures related to IMN and PD. Data such as length of hospital stay, infectious complications, non-infectious complications, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), mortality, systemic inflammatory response syndrome (SIRS) duration, IL-6, and C-reactive protein (CRP) were extracted, and meta-analyses were performed on these data to study their pooled results, heterogeneity, and publication bias. RESULTS: This meta-analysis involved 10 studies and a total of 572 patients. The results showed that the use of IMN significantly reduced the length of hospital stay for PD patients (MD = -2.31; 95% CI = -4.43, -0.18; P = 0.03) with low heterogeneity. Additionally, the incidence of infectious complications was significantly reduced (MD = 0.42; 95% CI = 0.18, 1.00, P = 0.05), with low heterogeneity after excluding one study. However, there was no significant impact on non-infectious complications, the incidence of POPF and DGE, mortality rates, duration of SIRS, levels of IL-6 and CRP. CONCLUSION: The use of IMN has been shown to significantly shorten hospital stays and decrease the frequency of infectious complications in PD patients. Early implementation of IMN is recommended for those undergoing PD. However, further research is needed to fully assess the impact of IMN on PD patients through larger and higher-quality studies.

Shuttle between arginine and lysine: influence on cancer immunonutrition.

Amino acids which are essential nutrients for all cell types' survival are also recognised to serve as opportunistic/alternative fuels in cancers auxotrophic for specific amino acids. Accordingly, restriction of amino acids has been utilised as a therapeutic strategy in these cancers. Contrastingly, amino acid deficiencies in cancer are found to greatly impair immune functions, increasing mortality and morbidity rates. Dietary and supplemental amino acids in such conditions have revealed their importance as 'immunonutrients' by modulating cellular homeostasis processes and halting malignant progression. L-arginine specifically has attracted interest as an immunonutrient by acting as a nodal regulator of immune responses linked to carcinogenesis processes through its versatile signalling molecule, nitric oxide (NO). The quantum of NO generated directly influences the cytotoxic and cytostatic processes of cell cycle arrest, apoptosis, and senescence. However, L-lysine, a CAT transporter competitor for arginine effectively limits arginine input at high L-lysine concentrations by limiting arginine-mediated effects. The phenomenon of arginine-lysine antagonism can, therefore, be hypothesised to influence the immunonutritional effects exerted by arginine. The review highlights aspects of lysine's interference with arginine-mediated NO generation and its consequences on immunonutritional and anti-cancer effects, and discusses possible alternatives to manage the condition. However, further research that considers monitoring lysine levels in arginine immunonutritional therapy is essential to conclude the hypothesis.

In vivo evidences of the health-promoting properties of bioactive compounds obtained from olive by-products and their use as food ingredient.

Olea europaea L. is the source of virgin olive oil (VOO). During its extraction, a high amount of by-products (pomace, mill wastewaters, leaves, stones, and seeds) is originated, which possess an environmental problem. If the generation of waste cannot be prevented, its economic value must be recovered and its effects on the environment and climate change must be avoided or minimized. The bioactive compounds (e.g., phenols, pectins, peptides) of these by-product fractions are being investigated as nutraceutical due to the beneficial properties it might have. In this review, the aim is to summarize the in vivo studies carried out in animals and humans with bioactive compounds exclusively obtained from olive by-products, aiming to demonstrate the potential health benefits these products can exert, as well as to describe its use in the food industry as bioactive ingredient. Several food matrices have been fortified with olive by-products fractions, leading to an improvement of properties. Animal and human studies suggest the benefits of ingesting olive-derived products to promote health. However, the investigation until now is scarce and consequently, well-designed human studies are required in order to fully address and confirm the safety and health-promoting properties of olive oil by-products.

DL-methionyl-DL-methionine as an efficient methionine source for promoting zootechnical performance and methionine-related pathways in the whiteleg shrimp (Penaeus vannamei).

Methionine (MET) supplementation is a current strategy to achieve shrimp requirement. Notwithstanding, the efficiency of the precisely formulated feeds can be diminished since shrimps are slow eaters and masticate feed externally that results in nutrient leaching. In this regard, a methionine dipeptide (DL-methionyl DL-methionine) benefits the feed industry by reducing MET water solubility while increasing its bioavailability. Therefore, the effects of feeding whiteleg shrimp (Penaeus vannamei) with increasing levels of methionine dipeptide were evaluated on zootechnical performance and methionine-, immune- and antioxidant-related pathways. A 74 d growth trial was conducted by feeding a control diet and four diets supplemented with AQUAVI® Met-Met at 0·08, 0·12, 0·24 and 0·32% of DM. Diet digestibility, body amino acids (AA) composition and nitrogen metabolites, metabolic enzymes, oxidative status and gene expression were evaluated. It can be concluded that graded dietary increase of methionine dipeptide up to 0·24 % for 74 d translated in significant gains on the growth performance, feed efficiency, nutrient and nitrogen gain and shrimp survival. Moreover, it was showed that Met-Met dietary spare leads to an improvement of free-AA pool and nitrogen metabolites concentration and reduces the signs of oxidative stress. Finally, in a closer look to the MET-related pathways passive to be altered by Met-Met spare, a clear modulation of the described antioxidant and cell proliferation routes was detected.

Is preoperative hypoalbuminemia or hypoproteinemia a reliable marker for anastomotic leakage risk in patients undergoing elective colorectal surgery in an enhanced recovery after surgery (ERAS) program?

PURPOSE: Preoperative hypoalbuminemia has traditionally been used as a marker of nutritional status and is considered a significant risk factor for anastomotic leak (AL). METHODS: The Westmead Enhanced Recovery After Surgery (WERAS) prospectively collected database, consisting of 361 patients who underwent colorectal surgery with primary anastomosis, was interrogated. Preoperative serum albumin and protein levels (measured within 1 week of surgery) were plotted on receiver operating characteristic curves (ROC curves) and statistically analyzed for cutoff values, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). RESULTS: The incidence of AL was 4.4% (16/361). Overall mortality was 1.4% (5/361), 6.3% (1/16) in the AL group, and 1.2% (4/345) in the no AL group. The median preoperative albumin and protein level in the AL group were 39 g/L and 75 g/L, respectively. The median preoperative albumin and protein level in the no AL group were 38 g/L and 74 g/L, respectively. The Mann-Whitney U test showed no statistically significant difference in albumin levels (p = 0.4457) nor protein levels (p = 0.6245) in the AL and no AL groups. ROC curves demonstrated that preoperative albumin and protein levels were not good predictors of anastomotic leak. Cutoff values for albumin (38 g/L) and protein (75 g/L) both had poor PPV for AL (4.8% and 3.8% respectively). CONCLUSION: In patients undergoing elective colorectal surgery as part of an ERAS program, preoperative serum albumin and protein levels are not reliable in predicting AL. This may be because of nutritional supplementation provided as part of an ERAS program may correct nutritional deficits to protect against AL or that low albumin/protein is not as robust a marker of AL as previously reported.

Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial.

BACKGROUND: Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients. METHODS: A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6). RESULTS: Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected. CONCLUSION: Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).

Mapping the global research landscape on nutritional support for patients with gastrointestinal malignancy: visualization analysis.

BACKGROUND: Early nutritional treatment is crucial for the care of patients with operable and advanced gastrointestinal malignancies. Therefore, much research has focused on nutritional support for patients with gastrointestinal malignancies. Therefore, this study aimed to evaluate the global scientific output and activity with respect to nutritional support and gastrointestinal malignancy. METHODS: We searched in Scopus for publications on gastrointestinal cancer and nutritional assistance published between January 2002 and December 2021. Then, using VOSviewer 1.6.18 and Microsoft Excel 2013, we conducted bibliometric analysis and visualization. RESULTS: A total of 906 documents were published between 2002 and 2021, including 740 original articles (81.68%) and 107 reviews (11.81%). China ranked first (298 publications, 32.89%), Japan ranked second (86 publications, 9.49%) and the USA ranked third (84 publications, 9.27%). The organisation with the highest number of publications was the Chinese Academy of Medical Sciences & Peking Union Medical College from China, with 14 articles, followed by the Peking Union Medical College Hospital from China and the Hospital Universitari Vall d'Hebron from Spain (13 publications for each). Before 2016, most studies focused on 'nutrition support for patients undergoing gastrointestinal surgery'. However, the latest trends showed that 'nutrition support and clinical outcomes in gastrointestinal malignancies' and 'malnutrition in patients with gastrointestinal cancer' would be more widespread in the future. CONCLUSIONS: This review is the first bibliometric study to provide a thorough and scientific analysis of gastrointestinal cancer and nutritional support trends worldwide over the last 20 years. This study can aid researchers in decision-making by helping them understand the frontiers and hotspots in nutrition support and gastrointestinal cancer research. Future institutional and international collaboration is expected to accelerate the advancement of gastrointestinal cancer and nutritional support research and investigate more efficient treatment methods.

The effect of perioperative immunonutritional support on nutritional and inflammatory status in patients undergoing lung cancer surgery: a prospective, randomized controlled study.

PURPOSE: Nutritional status is affected in patients who undergo lung cancer surgery (LCS). This study is aimed at investigating the effects of the use of immunonutritional support in the perioperative period on nutritional and inflammatory status in patients undergoing LCS. METHODS: A single-center, prospective, randomized controlled clinical trial was conducted with seventy patients planning to have LCS and randomized into treatment (TG) and control groups (CG). Immunonutritional support was given orally twice a day for ten days before the operation and five days after the operation in the treatment group. The nutritional status of the patients was screened with the Patient-Generated Subjective Global Assessment (PG-SGA); the Prognostic Nutrition Index (PNI) and the Systemic Inflammation Index (SII) were calculated. The physical activity status was assessed with the Eastern Cooperative Oncology Group Performance Status (ECOG-PS). RESULTS: Post-op nutritional status of the TG patients was better than the CG group (p = 0.009). Post-operative PG-SGA score was higher than preoperative PG-SGA score in both groups (p < 0.001). In the post-operative period, nutritional status (in terms of PG-SGA score category) in the patients in the TG was better than the CG (p = 0.046). In both groups, post-op ECOG score was higher than the pre-op ECOG score (p < 0.001). Post-op physical performance status was found to be better in the TG compared to the CG (p = 0.001). PNI level decreased statistically and significantly in the post-op period compared to the pre-op period, SII levels increased. CONCLUSION: Patients who will undergo LCS should be supported in terms of immunonutrition starting from the preoperative period.

Re-assessing the role of peri-operative nutritional therapy in patients with pancreatic cancer undergoing surgery: a narrative review.

Pancreatic cancer is the most common medical condition that requires pancreatic resection. Over the last three decades, significant improvements have been made in the conditions and procedures related to pancreatic surgery, resulting in mortality rates lower than 5%. However, it is important to note that the morbidity in pancreatic surgery remains r latively high, with a percentage range of 30-60%. Pre-operative malnutrition is considered to be an independent risk factor for post-operative complications in pancreatic surgery, such as impaired wound healing, higher infection rates, prolonged hospital stay, hospital readmission, poor prognosis, and increased morbidity and mortality. Regarding the post-operative period, it is crucial to provide the best possible management of gastrointestinal dysfunction and to handle the consequences of alterations in food digestion and nutrient absorption for those undergoing pancreatic surgery. The European Society for Clinical Nutrition and Metabolism (ESPEN) suggests that early oral feeding should be the preferred way to initiate nourishing surgical patients as it is associated with lower rates of complications. However, there is ongoing debate about the optimal post-operative feeding approach. Several studies have shown that enteral nutrition is associated with a shorter time to recovery, superior clinical outcomes and biomarkers. On the other hand, recent data suggest that nutritional goals are better achieved with parenteral feeding, either exclusively or as a supplement. The current review highlights recommendations from existing evidence, including nutritional screening and assessment and pre/post-operative nutrition support fundamentals to improve patient outcomes. Key areas for improvement and opportunities to enhance guideline implementation are also highlighted.

Perioperative Nutritional Considerations in Colon and Rectal Surgery.

Malnutrition is common in surgical patients and is associated with substantially increased morbidity and mortality. Dedicated assessment of nutritional status is advised by major nutrition and surgical societies. Assessment may utilize comprehensive and validated nutritional assessment tools or targeted history, physical examination with accompanying serologic markers to identify nutritional risk preoperatively. Emergent surgery in malnourished patients should proceed as the clinical situation dictates with consideration of ostomy or primary anastomosis with proximal fecal diversion to mitigate postoperative infectious complications. Nonemergent surgery should be delayed to facilitate nutritional optimization via oral nutritional supplementation preferably and total parenteral nutrition if necessary for at least 7 to 14 days. Exclusive enteral nutrition may be considered to optimize nutritional status and inflammation in patients with Crohn's disease. Immunonutrition use in the preoperative setting is not supported by evidence. Perioperative and postoperative immunonutrition may be of benefit but requires dedicated study in the contemporary era. Close attention to preoperative nutritional status and optimization represents a critical opportunity to improve outcomes in patients undergoing colorectal surgery.

Multicentre, randomised, open-label, parallel-group, clinical phase II study to evaluate immunonutrition in improving efficacy of immunotherapy in patients with metastatic non-small cell lung cancer, undergoing systematic nutritional counseling.

BACKGROUND: Nutritional support, including nutritional counseling and oral nutritional supplements (ONS), has been recommended as a first-line strategy in patients with non-small cell lung cancer (NSCLC). Evidence on the efficacy of immunonutrition during immunotherapy in these patients is positive, but still limited some secondary endpoints, such as treatment toxicity and tolerance. We hypothesize that early systematic provision of ONS with a high-protein-high calorie mixture containing immunonutrients (Impact®) in addition to nutritional counseling, compared to nutritional counseling alone, is beneficial to patients with NSCLC receiving immunotherapy with or without chemotherapy. We designed the present study to evaluate the efficacy of early systematic provision of ONS enriched with immunonutrients compared to nutritional counseling alone, in patients with NSCLC undergoing immunotherapy. Study endpoints were: treatment response (primary endpoint: progression-free survival), treatment tolerance and toxicity, body weight, body composition, protein-calorie intake, quality of life, fatigue, muscle strength and immunological profile. METHODS: This is a pragmatic, multicentre, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial (N = 180). DISCUSSION: The improvement of efficacy of nutritional support in oncology still deserves many efforts. Immunonutrition represents a promising approach also in patients with NSCLC, but evidence on its efficacy on clinical outcomes during immunotherapy is still inconclusive. The present pilot study, which guarantees early high-quality nutritional care (assessment and treatment) to all patients in agreement with current guidelines and recommendations, could represent one of the first proofs of efficacy of early oral immunonutrition in patients with cancer undergoing immunotherapy. Further large randomized trials addressing the improvement of supportive care could be hypothesized, accordingly. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov Identifier: NCT05384873.

Omega-6 sparing effects of parenteral lipid emulsions-an updated systematic review and meta-analysis on clinical outcomes in critically ill patients.

BACKGROUND: Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed. RESULTS: 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care. CONCLUSION: Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact. Trial registration PROSPERO international prospective database of systematic reviews (CRD42021259238).

Network meta-analysis of the optimal time of applying enteral immunonutrition in esophageal cancer patients receiving esophagectomy.

BACKGROUND: Enteral immunonutrition (EIN) has been extensively applied in cancer patients; however, its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN. METHODS: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Meta-analysis with head-to-head approach and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 software. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes. RESULTS: Total 14 studies involving 1071 patients were included. Meta-analysis with head-to-head approach indicated no difference between EIN regardless of the application time and standard EN (SEN); however, subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR = 0.47; 95%CI = 0.26 to 0.84; p = 0.01) and pneumonia (OR = 0.47; 95%CI = 0.25 to 0.90; p = 0.02) and shortened the length of hospitalization (LOH) (MD = - 1.01; 95%CI = - 1.44 to - 0.57; p < 0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes. CONCLUSIONS: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/KJ9UY.

Crohn's Disease, Host-Microbiota Interactions, and Immunonutrition: Dietary Strategies Targeting Gut Microbiome as Novel Therapeutic Approaches.

Crohn's disease (CD) is a complex, disabling, idiopathic, progressive, and destructive disorder with an unknown etiology. The pathogenesis of CD is multifactorial and involves the interplay between host genetics, and environmental factors, resulting in an aberrant immune response leading to intestinal inflammation. Due to the high morbidity and long-term management of CD, the development of non-pharmacological approaches to mitigate the severity of CD has recently attracted great attention. The gut microbiota has been recognized as an important player in the development of CD, and general alterations in the gut microbiome have been established in these patients. Thus, the gut microbiome has emerged as a pre-eminent target for potential new treatments in CD. Epidemiological and interventional studies have demonstrated that diet could impact the gut microbiome in terms of composition and functionality. However, how specific dietary strategies could modulate the gut microbiota composition and how this would impact host-microbe interactions in CD are still unclear. In this review, we discuss the most recent knowledge on host-microbe interactions and their involvement in CD pathogenesis and severity, and we highlight the most up-to-date information on gut microbiota modulation through nutritional strategies, focusing on the role of the microbiota in gut inflammation and immunity.

Effect of enteral immunonutrition compared with enteral nutrition on surgical wound infection, immune and inflammatory factors, serum proteins, and cellular immunity in subjects with gastric cancer undergoing a total gastrectomy: A meta-analysis.

We performed a meta-analysis to evaluate the effect of enteral immunonutrition compared with enteral nutrition on surgical wound infection, immune and inflammatory factors, serum proteins, and cellular immunity in subjects with gastric cancer undergoing a total gastrectomy. A systematic literature search up to November 2021 was done, and 10 studies included 1056 subjects with gastric cancer undergoing a total gastrectomy at the start of the study: 505 of them were provided with enteral immunonutrition, and 551 were enteral nutrition. They were reporting relationships about the effect of enteral immunonutrition compared with enteral nutrition on surgical wound infection, immune and inflammatory factors, serum proteins, and cellular immunity in subjects with gastric cancer undergoing a total gastrectomy. We calculated the odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CIs) to assess the effect of enteral immunonutrition compared with enteral nutrition on surgical wound infection, immune and inflammatory factors, serum proteins, and cellular immunity in subjects with gastric cancer undergoing a total gastrectomy using the dichotomous or contentious method with a random or fixed-effect model. Enteral immunonutrition had no significant difference in the surgical wound infection (OR, 0.77; 95% CI, 0.50-1.19, P = .24), the infectious complication (OR, 0.72; 95% CI, .48-1.09, P = .13), the systemic inflammatory response syndrome (MD, -0.50; 95% CI, -1.40 to 0.39, P = .27), the CD8+ level (MD, 1.34; 95% CI, 0-2.68, P = .05), the CD4+ level (MD, 1.21; 95% CI, -7.65 to 10.07, P = .79), the CD4-CD8+ (MD, 0.55; 95% CI, 0-1.10, P = .05), the lymphocyte (MD, -0.77; 95% CI, -1.87 to 0.33, P = .17), and the transferrin (MD, 0.03; 95% CI, -0.01 to 0.08, P = .14) compared with enteral nutrition in subjects with gastric cancer undergoing a total gastrectomy. However, enteral immunonutrition had significantly higher proalbumin (MD, 22.15; 95% CI, 3.57-40.72, P = .02), IgM (MD, 0.47; 95% CI, 0.43-0.50, P < .001), and IgG (MD, 1.98; 95% CI, 1.08-2.89, P < .001) compared with enteral nutrition in subjects with gastric cancer undergoing a total gastrectomy. Enteral immunonutrition had no significant difference in the surgical wound infection, the infectious complication, the systemic inflammatory response syndrome, the CD8+ level, the CD4+ level, the CD4+/CD8+, the lymphocyte, and the transferrin, and had significantly higher proalbumin, IgM, and IgG compared with enteral nutrition in subjects with gastric cancer undergoing a total gastrectomy. Further studies are required to validate these findings or to affect the confidence level.