Sepsis during short bowel syndrome hospitalizations:Identifying trends,disparities,and clinical outcomes in the United States

BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.

Navigating Long-Term Management Challenges in Short Bowel Syndrome: A Case Report of Chronic Intestinal Failure Complicated by Kidney Dysfunction

The most common cause of intestinal failure is short bowel syndrome (SBS), occurring as a result of a small functional intestine length, usually less than 200 cm, leading to intestinal malabsorption. A 59-year-old female with a past medical history of Crohns disease status post total colectomy with ileostomy over 20 years ago came to the hospital due to progressive weakness. Despite medical management, the patient had high ileostomy output, leading to electrolyte disbalance, metabolic acidosis, dehydration, and progressive kidney decline. Due to the high dependence on continuous fluid supplementation, it was decided to place a port for parenteral hydration to maintain fluid replacements and homeostasis after discharge. Prompt initiation of parenteral fluid replacement and close follow-up on patients with ileostomy and intestinal failure is strongly recommended to avoid complications and prevent intestinal, liver, or kidney transplants.

Chronic intestinal failure and short bowel syndrome in Crohn’s disease

Chronic intestinal failure(CIF)is a rare but feared complication of Crohn’s disease.Depending on the remaining length of the small intestine,the affected intestinal segment,and the residual bowel function,CIF can result in a wide spectrum of symptoms,from single micronutrient malabsorption to complete intestinal failure.Management of CIF has improved significantly in recent years.Advances in home-based parenteral nutrition,in particular,have translated into increased survival and improved quality of life.Nevertheless,60%of patients are permanently reliant on parenteral nutrition.Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy.The outcomes of patients with CIF could be greatly improved by more effective prevention,understanding,and treatment.In complex cases,the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation,nutritional support,and an improved quality of life.Here,we summarize current literature on CIF and short bowel syndrome,encompassing epidemiology,pathophysiology,and advances in surgical and medical management,and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.

Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation

Short bowel syndrome （SBS） refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn＇s disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 （GLP-2） is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is atrophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor （GLP-2R） remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

Glucagon-like peptide-2 analogues for Crohn’s disease patients with short bowel syndrome and intestinal failure

Short bowel syndrome(SBS)with intestinal failure(IF)is a rare but severe complication of Crohn’s disease(CD),which is the most frequent benign condition that leads to SBS after repeated surgical resections,even in the era of biologics and small molecules.Glucagon-like peptide-2 analogues have been deeply studied recently for the treatment of SBS-IF.These drugs have a significant intestinotrophic effect and the potential to reduce the chronic dependence of SBSIF patients on parenteral support or nutrition.Teduglutide has been approved for the treatment of SBS-IF,and apraglutide is currently in clinical development.The use of these drugs was examined with a focus on their use in CD patients.

Rehabilitation therapy for short bowel syndrome

OBJECTIVE: To investigate the effect of rehabilitation therapy for short bowel syndrome on patient nutritional status and intestinal adaptation. METHODS: The rehabilitation therapy included enteral or parenteral nutrition, glutamine, recombinant human growth hormone and rehabilitative diet. From January 1997 to July 2000, twenty - seven patients with short bowel syndrome received the treatment. The average age of the patients was 38.5 +/- 19.3 years, and the length of residual small intestine ranged from 15 to 80 cm, with an average of 46.8 +/- 23.4 cm. The ileocecal valve was preserved in 14 cases, and the average time between the onset of short bowel syndrome and the rehabilitation therapy was 86 +/- 105 days. RESULTS: After the treatment, nutritional status of the patients improved markedly, and intestinal absorptive capacity improved. Eight patients were followed up for more than 2 years, among whom 4 (50%) were weaned from total parenteral nutrition. Thirteen patients were followed up for more than 1 year, and 10 patients (76.9%) were weaned from total parenteral nutrition. CONCLUSIONS: Rehabilitation therapy for short bowel syndrome can improve patient nutritional status effectively and promote intestinal adaptation, providing a new hope for these patients. The therapeutic effects are related to the length of the residual small intestine, patients age and duration between massive intestinal resection and start of the treatment. Early initiation of rehabilitation therapy promotes intestinal adaptation and increases patients ability to wean from total parenteral nutrition.

Management of patients with a short bowel

There are two common types of adult patient with a short bowel, those with jejunum in continuity with a functioning colon and those with a jejunostomy. Both groups have potential problems of undernutrition, but this is a greater problem in those without a colon, as they do not derive energy from anaerobic bacterial fermentation of carbohydrate to short chain fatty acids in the colon. Patients with a jejunostomy have major problems of dehydration, sodium and magnesium depletion all due to a large volume of stomal output. Both types of patient have lost at least 60 cm of terminal ileum and so will become deficient of vitamin B(12). Both groups have a high prevalence of gallstones (45%) resulting from periods of biliary stasis. Patients with a retained colon have a 25% chance of developing calcium oxalate renal stones and they may have problems with D(-) lactic acidosis. The survival of patients with a short bowel, even if they need long-term parenteral nutrition, is good.

Effect of bowel rehabilitative therapy on structural adaptation of remnant small intestine: animal experiment

AIM: To investigate the individual and the combined effects of glutamine, dietary fiber, and growth hormone on the structural adaptation of the remnant small bowel. METHODS: Forty-two adult male Sprague-Dawley rats underwent 85% mid-small bowel resection and received total parenteral nutrition (TPN) support during the first three postoperational days.From the 4th postoperational day, animals were randomly assigned to receive 7 different treatments for 8 days: TPNcon group, receiving TPN and enteral 20 g x L(-1) glycine perfusion; TPN+Gln group, receiving TPN and enteral 20 g x L(-1) glutamine perfusion; ENcon group, receiving enteral nutrition (EN) fortified with 20 g x L(-1) glycine; EN+Gln group, enteral nutrition fortified with 20 g x L(-1) glutamine; EN+Fib group, enteral nutrition and 2 g x d(-1) oral soybean fiber; EN+GH group, enteral nutrition and subcutaneous growth hormone (GH) (0.3 IU) injection twice daily; and ENint group, glutamine-enriched EN, oral soybean fiber, and subcutaneous GH injection. RESULTS: Enteral glutamine perfusion during TPN increased the small intestinal villus height (jejunal villus height 250 microm +/- 29 microm in TPNcon vs 330 microm +/- 54 microm in TPN+Gln, ileal villus height 260 microm +/- 28 microm in TPNcon vs 330 microm +/- 22 microm in TPN+Gln, P【0.05) and mucosa thickness (jejunal mucosa thickness 360 microm +/- 32 microm in TPNcon vs 460 microm +/- 65 microm in TPN+Gln, ileal mucosa thickness 400 microm +/- 25 microm in TPNcon vs 490 microm +/- 11 microm in TPN+Gln,P【 0.05) in comparison with the TPNcon group. Either fiber supplementation or GH administration improved body mass gain (end body weight 270 g +/- 3.6g in EN+Fib, 265.7 g +/- 3.3 g in EN+GH, vs 257 g +/- 3.3 g in ENcon, P【 0.05), elevated plasma insulin-like growth factor (IGF-I) level (880 microg x L(-1). 52 microg x L-(-1) in EN+Fib,1200 microg x L(-1). 96 microg x L-(-1) in EN +/- GH, vs 620 microg x L(-1).43 microg x L-(-1) in ENcon, P【 0.05), and increased the villus height (jejunum 560 microm +/- 44 microm in EN +/- Fib, 530 microm +/- 30 microm in EN +/- GH, vs 450 microm +/- 44 microm in ENcon, ileum 400 microm +/- 30 microm in EN+Fib, P【0.05) and the mucosa thickness (jejunum 740 microm +/- 66 microm in EN +/- Fib, 705 microm +/- 27 microm in EN +/- GH, vs 608 microm +/- 58 microm in ENcon, ileum 570 microm +/- 27 microm in EN +/- Fib, 560 microm +/- 56 microm in remnant jejunum and ileum. Glutamine-enriched EN produced little effect in body mass, plasma IGF-I level, and remnant small bowel mucosal structure. The ENint group had greater body mass (280 g +/- 2.2g), plasma IGF-I level (1450 microg x L(-1). 137 microg x L-(-1)), and villus height (jejunum 620 microm +/- 56 microm, ileum 450 microm +/- 31 microm) and mucosal thickness (jejunum 800 microm +/- 52 microm, ileum 633 microm +/- 33 microm) than those in ENcon, EN+Gln (jejunum villus height and mucosa thickness 450 microm +/- 47 microm and 610 +/- 63 microm, ileum villus height and mucosa thickness 330 microm +/- 39 microm and 500 microm +/- 52 microm), EN+GH groups (P【0.05), and than those in EN+Fib group although no statistical significance was attained. CONCLUSION: Both dietary fiber and GH when used separately can enhance the postresectional small bowel structural adaptation. Simultaneous use of these two gut-trophic factors can produce synergistic effects on small bowel structural adaptation. Enteral glutamine perfusion is beneficial in preserving small bowel mucosal structure during TPN, but has little beneficial effect during EN.

Effect of Enteral Nutrition Formula on Fat Absorption and Serum Free Fatty Acid Profiles in Rat with Short-Bowel Syndrome

The effects of enteral nutrition containing long chain triglycerides （LCT） and medium chain triglycerides （MCT） or L-arginine （Arg） on fat absorbability, serum free fatty acid profiles and intestinal morphology in rats with short-bowel syndrome （SBS） were studied using gas chromatography. Twenty-eight Sprague-Dawley rats were randomly assigned to 4 groups： sham operation fed with LCT as control; 85% small bowel resection fed with LCT, MCT/LCT, and Arg/LCT, respectively. SBS rats showed a decrease of fat absorptivity. Enteral nutrition supplemented with MCT could increase fat absorptivity. L-Arginine enhanced enteral nutrition was associated with the elevation of fat absorptivity, possibly due to its enterotrophic effect on remnant small bowel mucosa. LCT group showed a significant deficiency of total free fatty acid and the decreased essential fatty acid content, which was improved in other two SBS groups.

Intestinal mucosal adaptation

Intestinal failure is a condition characterized by malnutrition and/or dehydration as a result of the inadequate digestion and absorption of nutrients. The most common cause of intestinal failure is short bowel syndrome, which occurs when the functional gut mass is reduced below the level necessary for adequate nutrient and water absorption. This condition may be congenital, or may be acquired as a result of a massive resection of the small bowel. Following resection, the intestine is capable of adaptation in response to enteral nutrients as well as other trophic stimuli. Identifying factors that may enhance the process of intestinal adaptation is an exciting area of research with important potential clinical applications.

Intestinal mucosal atrophy and adaptation

Mucosal adaptation is an essential process in gut ho- meostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical out- comes can be improved by manipulating the physiol- ogy of adaptation. This review will summarize current understanding of the basic science surrounding adapta- tion, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clini- cal outcomes.

Morphological,kinetic,membrane biochemical and genetic aspects of intestinal enteroplasticity

The process of intestinal adaptation("enteroplasticity") is complex and multifaceted.Although a number of trophic nutrients and non-nutritive factors have been identified in animal studies,successful,reproducible clinical trials in humans are awaited.Understanding mechanisms underlying this adaptive process may direct research toward strategies that maximize intestinal function and impart a true clinical benefit to patients with short bowel syndrome,or to persons in whom nutrient absorption needs to be maximized.In this review,we consider the morphological,kinetic and membrane biochemical aspects of enteroplasticity,focus on the importance of nutritional factors,provide an overview of the many hormones that may alter the adaptive process,and consider some of the possible molecular profiles.While most of the data is derived from rodent studies,wherever possible,the results of human studies of intestinal enteroplasticity are provided.