Immediate Oral Refeeding in Patients With Mild and Moderate Acute Pancreatitis: A Multicenter, Randomized Controlled Trial (PADI trial).

OBJECTIVE: To establish the optimal time to start oral refeeding in mild and moderate acute pancreatitis (AP) to reduce hospital length-of-stay (LOS) and complications. SUMMARY BACKGROUND DATA: Oral diet is essential in mild and moderate AP. The greatest benefits are obtained if refeeding starts early; however, the definition of "early" remains controversial. METHODS: This multicenter, randomized, controlled trial (NCT03829085) included patients with a diagnosis of mild or moderate AP admitted consecutively to 4 hospitals from 2017 to 2019. Patients were randomized into 2 treatment groups: immediate oral refeeding (IORF) and conventional oral refeeding (CORF). The IORF group (low-fat-solid diet initiated immediately after hospital admission) was compared to CORF group (progressive oral diet was restarted when clinical and laboratory parameters had improved) in terms of LOS (primary endpoint), pain relapse, diet intolerance, complications, and, hospital costs. RESULTS: One hundred and thirty one patients were included for randomization. The mean LOS for the IORF and CORF groups was 3.4 (SD ± 1.7) and 8.8 (SD ± 7.9) days, respectively (P < 0.001). In the CORF group alone, pain relapse rate was 16%. There were fewer complications (8% vs 26%) and health costs were twice as low, with a savings of 1325.7€/patient in the IORF than CORF group. CONCLUSIONS: IORF is safe and feasible in mild and moderate AP, resulting in significantly shorter LOS and cost savings, without causing adverse effects or complications.

Effects of Short-Peptide-Based Enteral Nutrition on the Intestinal Microcirculation and Mucosal Barrier in Mice with Severe Acute Pancreatitis.

SCOPE: Short-peptide-based enteral nutrition (SPEN) is absorbed more efficiently in patients with severe acute pancreatitis (SAP). More importantly, SPEN decreases SAP-induced enterogenous infection risk. This study aims to investigate whether SPEN alleviates intestinal bacterial translocation in mice with SAP, and the underlying mechanisms. METHODS AND RESULTS: The SAP model is established after pre-treatment with SPEN or intact-protein-based enteral nutrition. Although there is no improvement in pancreas injury, as evaluated through Hematoxylin-Eosin staining or serum amylase, SPEN obviously attenuates intestinal bacterial translocation after SAP. To unveil the mechanisms, it is found that the intestinal mechanical barrier destroyed by SAP is significantly relieved by SPEN, which presents with recovered ZO-1 expression, mucus layer, and goblet cell function. Additionally, SPEN alleviates local CCR6/CCL20 induced CD11c+ dendritic cell infiltration, systemic immunosuppression, and inhibits the secretion of luminal secretory immunoglobulin A. Possibly responsible for SAP-induced mucosal dysfunctions, destroyed intestinal mucosal microcirculation and local hypoxia are largely improved in SAP+SPEN group. CONCLUSION: SPEN can improve downregulated intestinal mucosal microcirculation secondary to SAP, which may be responsible for mucosal inflammation relief, maintenance of the mechanical barrier and mucosal immunity, the correction of systemic immunosuppression, and play a protective role in defending commensal bacterial translocation after SAP.

Dietary pomegranate supplement alleviates murine pancreatitis by modulating Nrf2-p21 interaction and controlling apoptosis to survival switch.

Dietary supplementation of polyphenol-rich pomegranate extract (POMx) has been shown to have anti-oxidant and anti-inflammatory activities. Here, we evaluate the efficacy of POMx in mitigating pancreatitis in mice and provide a mechanistic outline of the process. Age-matched male Swiss albino mice were injected with Lipopolysaccharide (LPS) and given POMx supplement alone or in combination with LPS. After 4 weeks of treatment histological scoring for pancreatic edema and vacuolization was performed. Serum insulin levels were estimated and the glucose tolerance test (IPGTT) data revealed that POMx reduced inflammation induced hyperglycemia in mice. Analysis of TLR4, IκB expression, and NF-κB nuclear translocation, and concentrations of IL-6 and TNFα showed that POMx is able to modulate the molecular instigators of inflammatory responses. Annexin V assay indicated that POMx protects against inflammation-mediated apoptosis in the pancreas. Expression profile of SAPK/JNK pathway, p53, Bax, Bcl-2 and Caspase-3 validate an apoptotic to survival shift in POMx treatment group. Co-immunoprecipitation studies show that POMx stabilizes p21 and Nrf2 interaction and increases its nuclear translocation. The study also proves that the nuclear fraction of Nrf2 is able to bind to the Bcl-2 promoter and activate an anti-apoptotic program. The findings of our study underline an anti-inflammatory, anti-oxidative and anti-apoptotic role of POMx and provide a mechanistic idea of how POMx confers protection during pancreatitis.

Guidance for supplemental enteral nutrition across patient populations.

Enteral nutrition is preferred over parenteral nutrition as a result of the greater safety of enteral nutrition therapy and comparative convenience. A wide variety of enteral nutrition products have been developed, including disease-specific products to help manage the nutritional needs of patients with kidney failure, liver failure, lung disease, diabetes, and other conditions. An assessment of each patient's nutritional needs and digestive function should be conducted prior to initiation of enteral nutrition therapy. Other considerations in determining the appropriate route and method of enteral nutrition administration include the time and nursing involvement required for administration, potential complications of medication administration, and concerns related to pancreatic dysfunction in certain groups. Tailored guidelines and treatment considerations are reviewed in this manuscript the application of enteral nutrition in various patient populations.

Familial chylomicronemia syndrome and response to medium-chain triglyceride therapy in an infant with novel mutations in GPIHBP1.

BACKGROUND: Severe hypertriglyceridemia predisposes to attacks of acute pancreatitis, a serious condition complicated by multiorgan failure, pancreatic necrosis, and mortality rates up to 20% in adults and 6.5% in children. OVERVIEW: We describe an infant who suffered from an episode of acute pancreatitis from severe hypertriglyceridemia. Two major challenges complicate the case: identifying the etiology of severe hypertriglyceridemia and finding an efficacious treatment. A thorough history, physical examination, and laboratory workup failed to identify a clear etiology, prompting a genetic workup that identified compound heterozygous mutations in the glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) gene. This patient's hypertriglyceridemia responded to an infant formula rich in medium chain triglycerides (MCTs), and she remained free of pancreatitis 6 months later. CONCLUSIONS: This case highlights the need to pursue a genetic evaluation in the absence of secondary causes of severe hypertriglyceridemia in infants. Patients with mutations in GPIHBP1 fail to respond to currently available lipid-lowering agents so dietary management-specifically, an extremely low-fat diet and supplementation with MCT-remains the cornerstone of therapy. Treatment in infants should focus on dietary measures rather than pharmacologic agents.

Atualidades em terapia nutricional na pancreatite aguda / News in nutritional therapy in acute pancreatitis

Objetivo: investigar na literatura científica as atuais recomendações emterapia nutricional na pancreatite aguda.Método: revisão na literatura científica, com ênfase em diretrizes e artigosde revisões sistemáticas publicados nos anos de 2007 a 2012, em revistas indexadas em bases de dados virtuais. As palavras-chave utilizadas foram: pancreatite aguda, terapia nutricional, nutrição enteral, nutrição parenteral. Um total de três diretrizes e 14 artigos de revisões sistemáticas foram utilizados. Resultados: a dieta por via oral, recomendada para a pancreatite aguda leve, é baseada na tolerância digestiva sem grandes alterações. A terapia nutricional enteral, quando indicada, deve considerar o início precoce, infusão contínua, posicionamento da sonda enteral, tipo de fórmula, uso de fórmula hiperproteica, normoglicídica e normolipídica, uso de triglicerídeos de cadeia média e de ácidos graxos ômega-3. A indicação da via parenteral só deve ocorrer na impossibilidade do uso do trato digestivo para a oferta de nutrientes de forma total ou parcial, com a adoção de procedimentos envolvendo oferta de calorias (25-30kcal/kg/dia não protéicas) e proteínas (1,25 a 1,5g/kg/dia) que podem ser reduzidasconforme quadro clínico, de macronutrientes (glicose contribuindocom 50% a 70% do total de calorias e os lipídios correspondendo a 0,8 a 1,5g/kg/dia) e micronutrientes, além da suplementação com glutamina (dosagem superior a 0,3 g/kg/dia). Conclusão: enquanto a dieta via oral nos casos da pancreatite aguda leve não exige atenção criteriosa, o contrário ocorre em relação à nutricional artificial (enteral e parenteral) e esforços são necessários para o aperfeiçoamento dos procedimentos que devem ser respaldados pela literatura científica.

Objective: To investigate the scientific literature on the current recommendations nutritional therapy in acute pancreatitis. Method: Review the scientific literature, with an emphasis on guidelines and systematic reviews of articles published in the years 2007 to 2012 in journals indexed in virtual databases. The keywords used were: acute pancreatitis, nutritional therapy, enteral nutrition, parenteral nutrition. Atotal of 14 articles and three guidelines for systematic reviews were used.Results: The oral diet, is recommended for mild acute pancreatitis, digestivetolerance is based on without major changes. The enteral nutrition therapy, when indicated, should consider early, continuous infusion, placement of enteral feeding, formulae type, use of high protein formulae, and adequate in glucose and lipids, use of medium chain triglycerides and omega-3. The indication of the parenteral route shouldonly occur in the impossibility to use the digestive tract for the supply ofnutrients in whole or in part, with the adoption of procedures involvingsupply of calories (25-30kcal/kg/day non protein) and proteins (1,25 to1.5g/kg/day) can be reduced as clinical, nutrients (glucose contributing50% to 70% of total calories and lipids corresponding to 0.8 to 1.5g/kg/day) and micronutrients in addition to supplementation with glutamine(dosage greater than 0.3 g/kg/day).Conclusion: While the oral diet in cases of mild acute pancreatitis does not require careful attention, the opposite occurs in relation to artificial nutrition (enteral and parenteral) and efforts are needed to improve the procedures that must be supported by the scientific literature.

Acute pancreatitis in obesity: adipokines and dietary fish oil.

BACKGROUND: Acute pancreatitis is a substantial clinical problem accounting for 240,000 hospital admissions yearly in the United States. Obesity is epidemic and is clearly an independent risk factor for increased severity of acute pancreatitis (AP). Adipose tissue is an endocrine organ that secretes a variety of metabolically active substances termed adipokines. However, the role of adipokines in modulating acute pancreatitis severity remains incompletely understood. Dietary fish oil is rich in omega-3 free fatty acids and attenuates adipose tissue-induced inflammation. Therefore, we hypothesized that feeding obese mice diets rich in fish oil would alter the adipokine milieu and attenuate the severity of pancreatitis. METHODS: Lean (C57BL/6 J) and obese (LepDb) mice were fed either a soybean oil- or fish oil-rich diet for 4 weeks. AP was induced by six hourly intraperitoneal injections of cerulein (50 µg/kg). Serum adipokine levels were measured, and pancreatitis severity was assessed histologically and by measuring pancreatic concentrations of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), myleoperoxidase (MPO), and monocyte chemoattractant protein-1 (MCP-1). RESULTS: Obese mice developed more severe pancreatitis than lean mice. Fish oil significantly decreased serum leptin (lean and obese) and increased serum adiponectin (lean only). Fish oil did not alter the baseline pancreatic inflammatory milieu, nor did it change histologic or biochemical pancreatitis severity. CONCLUSION: These data demonstrate that a diet rich in fish oil altered the adipokine milieu in lean and congenitally obese mice; however, fish oil did not improve pancreatitis severity induced with cerulein hyperstimulation.

La nutrición enteral puede mejorar la evolución de la pancreatitis aguda grave? / Can enteral nutriton improve the course of severe acute pancreatitis?

La mayoría de los casos de pancreatitis aguda se presentan como formas leves en las que no se recomienda el soporte nutricional a no ser que los pacientes no puedan reanudar su alimentación oral normal después de 5-7 días. Por el contrario, la pancreatitis grave cursa con estrés metabólico y precisa de soporte nutricional precoz. La nutrición enteral, como parte del tratamiento de la pancreatitis aguda, lleva más de una década. Estudios recientes indican que la nutrición enteral puede mejorar la evolución de la pancreatitis aguda grave, reducir las complicaciones y favorecer una recuperación más rápida de la enfermedad. La inmunonutrición y los probióticos combinados con la nutrición enteral son una alternativa promisoria, pero son necesarios estudios multicéntricos bien diseñados para establecer su rol en la pancreatitis aguda.

Most of acute pancreatitis cases present as mild cases for which nutritional support is not recommended provided the patient is able to restart normal oral intake within 5- days. By contrast, severe pancreatitis associates metabolic stress and requires early nutritional support. The application of enteral feeding as part of the treatment of acute pancreatitis goes back more than a decade now. Recent studies show that enteral nutrition may improve the course of severe acute pancreatitis, reduce its complications and promote a quicker improvement from the disease. Inmunonutrition and probiotics combined with enteral nutrition are a potentially promising alternative, but further well-designed multi-centric trials are necessary to prove their role in the treatment of acute pancreatitis.

Videothoracoscopic treatment of a rare complication of nasojejunal tube insertion.

OBJECTIVE: Intubation of the tracheobronchial tree is the most common type of malposition during the placement of narrow-bore enternal tubes. CASE REPORT: In addition to other treatment components in a 65-year-old female, nasojejunal feeding was started to treat her for severe acute pancreatitis. After the placement of the narrow-bore feeding tube, she developed dyspnea and huskiness. On auscultation and X-ray investigation, the right pneumothorax was detected and the tube was found in the chest cavity. The diagnosis was confirmed by bronchoscopy. Videothoracoscopic resection and closure of the lacerated lung, using a tube thoracostomy, were performed. The patient recovered after postoperative conservative treatment for her pancreatitis. CONCLUSION: Pneumothorax and laceration of the lung-caused by the malposition of narrow-bore enternal tube-can be successfully treated by applying videothoracoscopy.

Parenteral nutrition and urban legends.

PURPOSE OF REVIEW: To assess the recent literature regarding parenteral nutrition to identify publications that have purported to support various beliefs about the utility of parenteral nutrition, and then to critically evaluate the data presented in those (as well as prior) publications. RECENT FINDINGS: Artificial nutrition improves nutritional markers but not clinical outcomes, suggesting that malnutrition is not causatively associated with a poor outcome. There are no convincing data that parenteral nutrition is beneficial in severely malnourished surgical patients. Glutamine supplementation of parenteral nutrition solutions may reduce the infectious complication rate, but it is unknown if glutamine-supplemented parenteral nutrition is better than no parenteral nutrition. Most, but not all, systematic reviews have demonstrated that enteral nutrition produces fewer problems than parenteral nutrition; no data suggest that either modality is better than doing no artificial nutrition. Randomized trials have not uniformly been able to demonstrate that parenteral nutrition is efficacious in acute pancreatitis. There is some, but not convincing, data that a regimen of glutamine, growth hormone, and a specialized diet will reduce the need for parenteral nutrition in patients with short bowel syndrome. SUMMARY: It is important for clinicians to be able to critically evaluate the medical literature.

Ertapenem-induced acute pancreatitis in a surgical elderly patient.

Case summary A 78-year old man was given, after surgery, 1 g ertapenem every 24 h intravenously. His clinical evolution was favorable and on day 8 ertapenem was discontinued and the patient was put on a semi-solid diet. On day 9, abdominal distension was seen accompanied by epigastric pain. The laboratory tests on day 8 showed an altered pancreatic profile: amylase = 1823 U/l (normal value: 0-100); lipase = 8045 U/l (normal value: 0-60); C-reactive protein (CRP) = 16.09 mg/dl (normal value: 0-0.5). Full Blood Count (FBC) showed leukocytosis with an increase in neutrophils and eosinophils. The prior pancreatic parameters were normal without leukocytosis. The evolution of clinical symptoms after discontinuing ertapenem was rapid. Between days 11 and 16, the laboratory parameters returned to normal values; the eosinophilia persisted longer, decreasing between days 14 and 16. Conclusions clinicians should include monitoring the development of acute pancreatitis in the safety parameters in patients undergoing treatment with this carbapenem.

A double-blind, randomised, controlled trial to study the effects of an enteral feed supplemented with glutamine, arginine, and omega-3 fatty acid in predicted acute severe pancreatitis.

CONTEXT: Current best evidence is in favour of early institution of enteral feeding in acute severe pancreatitis with promising results from trials in immunonutrition on other patient groups. OBJECTIVE: To identify which groups of patients and products are associated with benefit, we investigated immunonutrition in patients with predicted acute severe pancreatitis. DESIGN: A randomised trial of a study feed containing glutamine, arginine, tributyrin and antioxidants versus an isocaloric isonitrogenous control feed was undertaken. PATIENTS: Thirty-one patients with a diagnosis of acute pancreatitis predicted to develop severe disease: 15 study feeds and 16 control feeds. INTERVENTIONS: Enteral feeding via nasojejunal tube for 3 days. If patients required further feeding the study was continued up to 15 days. MAIN OUTCOME MEASURES: Reduction in C-reactive protein (CRP) by 40 mg/L after 3 days of enteral feeding was the primary endpoint. Carboxypeptidase B activation peptide (CAPAP) levels were taken at regular intervals. RESULTS: After 3 days of feeding, in the study group 2/15 (13%) of patients had reduced their CRP by 40 mg/L or more. In the control group 6/16 (38%) of patients had reduced their CRP by this amount. This difference was found to be near the statistical significant limit (P=0.220). CONCLUSIONS: The cause of the unexpectedly higher CRP values in the study group is unclear. The rise in CRP was without a commensurate rise in CAPAP or outcome measures so there was no evidence that this represented pancreatic necrosis. The contrast between the CRP and CAPAP results is of interest and we believe that specific pancreatic indices such as CAPAP should be considered in larger future studies.

Nutrição enteral por sonda de triplo lume na pancreatite aguda grave / Enteral feeding tube of triple lumen in severe acute pancreatitis / Sonda de alimentación enteral de triple lumen en la pancreatitis aguda grave

A pancreatite aguda é uma doença inflamatória do pãncreas que compromete, de maneira variável, os tecidos peri-pancreáticos e os sistemas orgãnicos distantes. Vinte por cento dos casos desenvolvem a forma grave da doença com complicações locais e ou falências orgãnicas. os pacientes com pancreatite aguda grave frequentemente necessitam terapia nutricional. Por várias décadas, a nutrição parenteral foi a única modalidade empregada, visando nutrir e possibilitar o repouso glandular. Nos últimos anos, a nutrição enteral pós-pilórica tornou-se a forma preferencial de terapia nutricional na pancreatite aguda grave, ficando a nutrição parenteral reservada para os casos com contra-indicações ou impossibilidade de usar a via enteral. Neste estudo, descrevem-se quatro casos de pancreatite aguda grave onde se utilizou nutrição jejunal com descompressão gástrica simultânea através da sonda Trelumina e discute-se o acesso enteral na pancreatite aguda grave.

Acute pancreatitis is an inflammatory disease of the pancreas that commits so variable, the peri-pancreatic tissues and organ systems distant. Twenty percent of cases develop a severe form of disease with local complications and / or organ failure. patients with severe acute pancreatitis often require nutritional therapy. For several decades, parenteral nutrition was the only method employed in order to nurture and allow the rest glandular. In recent years, the post-pyloric enteral nutrition has become the preferred form of nutrition therapy in severe acute pancreatitis, parenteral nutrition being reserved for cases with contraindications or inability to use the enteral route. In this study, we describe four cases of severe acute pancreatitis which was used jejunal nutrition with simultaneous gastric decompression through the probe Trelumina and discusses the enteral access in severe acute pancreatitis.

La pancreatitis aguda es una enfermedad inflamatoria del páncreas que compromete a tan variable, los tejidos peri-pancreática y sistemas de órganos distantes. Veinte por ciento de los casos se desarrollan una forma severa de la enfermedad con complicaciones locales y / o insuficiencia de órganos. pacientes con pancreatitis aguda grave a menudo requieren terapia nutricional. Durante varias décadas, la nutrición parenteral era el único método empleado con el fin de nutrir y permitir que el resto glandular. En los últimos años, la nutrición enteral post-pilórica se ha convertido en la forma preferida de la terapia nutricional en la pancreatitis aguda grave, la nutrición parenteral se reserva para casos con contraindicaciones o la imposibilidad de usar la vía enteral. En este estudio, se describen cuatro casos de pancreatitis aguda grave que se utilizó la nutrición yeyunal con la descompresión gástrica simultánea a través de la sonda Trelumina y discute el acceso enteral en la pancreatitis aguda grave.

Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis.

BACKGROUND: Microbial infection of the pancreatic tissue in patients with severe acute pancreatitis increases the morbidity and mortality rates. Colonization of the lower gastrointestinal tract and oropharynx with Gram-negative, but sometimes also Gram-positive, bacteria precedes contamination of the pancreas. The aim of this study was to determine whether lactic acid bacteria such as Lactobacillus plantarum 299 could prevent colonization of the gut by potential pathogens and thus reduce the endotoxaemia associated with acute pancreatitis. METHODS: Patients with acute pancreatitis were randomized into two double-blind groups. The treatment group received a freeze-dried preparation containing live L. plantarum 299 in a dose of 109 organisms, together with a substrate of oat fibre, for 1 week by nasojejunal tube. The control group received a similar preparation but the Lactobacillus was inactivated by heat. RESULTS: A total of 45 patients completed the study. Twenty-two patients received treatment with live and 23 with heat-killed L. plantarum 299. Infected pancreatic necrosis and abscesses occurred in one of 22 patients in the treatment group, compared with seven of 23 in the control group (P = 0.023). The mean length of stay was 13.7 days in the treatment group versus 21.4 days in the control group (P not significant). CONCLUSION: Supplementary L. plantarum 299 was effective in reducing pancreatic sepsis and the number of surgical interventions.