Физическое развитие и компонентный состав тела детей в катамнезе после перенесенной резекции кишечника в неонатальном периоде

Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cells (ECs) proliferation as well as apoptosis. Angiotensin-converting enzyme (ACE) has been shown to regulate ECs apoptosis. In this study, we investigated the effect of ACE inhibition on intestinal adaptation after small bowel resection (SBR) in a rat model. Sprague-Dawley rats were used and were divided into four groups: (1) Sham group received an ileum transection (n = 6); (2) Sham + ACE-I group received an ileum transaction and lavage with ACE inhibitor (ACE-I, enalaprilat, 2 mg/kg/day) (n = 6); (3) SBS group received a 70 % mid-intestinal resection (n = 6); (4) SBS + ACE-I group received a 70 % mid-intestinal resection and lavage with enalaprilat (2 mg/kg/day) (n = 6). Sampling was done 10 days after surgery. ECs apoptosis was studied by TUNEL staining. ACE, angiotensin II (ANGII) receptor type 1 (AT1R) and receptor type 2 (AT2R) expressions were detected with RT-PCR and immunofluorescent confocal microscopy. SBR leads to significant intestinal hypertrophy. The addition of ACE-I to SBS rat resulted in a significant decline in ECs apoptosis. ACE mRNA expression was significantly elevated after SBS creation (0.24 ± 0.07 vs. 0.42 ± 0.11), and ACE-I administration further increased mucosal ACE mRNA expression (0.54 ± 0.12). Interestingly, AT1R mRNA expression showed a significant decline in the SBS group compared to Sham levels, and ACE-I administration increased AT1R mRNA expression to Sham levels. No significant difference in AT2R mRNA expression was found between Sham and SBS group. These results offer further insight into the role of ACE on intestinal mucosal remolding after massive bowel resection. ACE-I may be beneficial to SBS patients via a reduction of the apoptotic rate, thus facilitating the degree of adaptation.

Introduction: Crohn’s disease is an inflammatory disorder of the gastrointestinal tract that can affect any part of the tract, ranging from the mouth to the perianal area. Depending on the location and severity of inflammation, small bowel resections might be necessary to control disease. Short Bowel Syndrome (SBS) is a common complication arising after extensive bowel resection, especially in medically refractory Crohn’s disease. These patients are at a high risk of adverse outcomes when hospitalized. The aim of this study was to analyze the impact of SBS for patients hospitalized for Crohn’s disease flare. Methods: All adult hospitalized patients from January 2016 to December 2019 in the nationwide inpatient sample (NIS) were captured. The sample population included all patients with a primary diagnosis of Crohn’s disease using ICD-10 codes (International Classification of Diseases, tenth edition). We then identified patients with a secondary diagnosis of SBS. The Crohn’s disease population was divided into patients with SBS (study group) and without SBS (control group). Linear regression was used for comparing continuous variables and Chi-square tests for categorical variables. Morbidity, mortality and healthcare utilization were analyzed using multivariate logistic and linear regression models where appropriate. Results: The sample size included 374,745 patients admitted for Crohn’s disease flare, of which 99.75% did not have underlying SBS while 0.25% did. Study group had a higher incidence of Hospital-acquired pneumonia (Adjusted OR (aOR) =2.93), Catheter related blood-stream infection (aOR=7.71) and Sepsis (aOR=2.99), all with p< 0.05 or less. There was also a higher risk of hyponatremia (aOR=1.79) and Iron-deficiency anemia (aOR=1.68) in the study group. No difference was noted in venous thromboembolism rates. The adjusted mean change in hospitalization charge was $44,359 and mean change in length of stay was 6.35 days in study group vs control. Mortality though was higher in SBS group, this lost significance following multivariate analysis. (Figure) Conclusion: SBS increases the risk of infections, electrolyte deficiency and anemia in patients admitted for Crohn’s disease flare but venous thromboembolism and mortality rates of both groups remains similar. This proves to be a huge burden on both the patients and the healthcare. The outcomes of patients with SBS could be greatly improved by more effective prevention of these complications, and treatment of high-risk Crohn’s patients more vigilantly. (Table) Table 1. - In-hospital outcomes Variables Crohn’s with no SBS* (Control) Crohn’s with SBS* (Study) p-value Hospital acquired pneumonia 0.78% 3.36% < 0.001 Adjusted odds ratio1=2.93 0.042 Catheter related blood-stream infection 0.1% 1.68% < 0.001 Adjusted odds ratio1=7.71 0.005 Sepsis 1.19%% 5.88% < 0.001 Adjusted odds ratio1=2.99 0.006 Septic shock 0.51% 2.52% 0.002 Adjusted odds ratio1 = 2.36 0.15 Hyponatremia 6.07% 16.81% < 0.001 Adjusted odds ratio1=1.79 0.02 Venous thrombo-embolism 0.77% 2.52% 0.02 Adjusted odds ratio1=1.84 0.29 Iron deficiency anemia 12.49% 31.09% < 0.001 Adjusted odds ratio1=1.68 0.045 Mean total hospitalization charge ($) $44,911 $100,203 < 0.001 Mean change in charges1 = $44,359 < 0.001 Mean length of stay (days) 4.78 12.53 < 0.001 Mean change in length of stay1 = 6.35 < 0.001 In-hospital mortality 0.2% 0.84% 0.11 Adjusted odds ratio1=2.44 0.39 *SBS- Short Bowel Syndrome 1Adjusted for Age, Sex, Race, income, hospital characteristics and Elixhauser score. Figure 1.: Graph 1.

Intestinal adaptation is important for the short bowel syndrome (SBS) patients. Growing evidence has suggested that bile salt dependent lipase (BSDL) not only has the lipolytic activity, but also the immune-modulating and pro-proliferative activities. The purpose of the present study was to investigate the effects of BSDL on intestinal adaptive growth and gut barrier function in a rat model of SBS. Twenty-four male Sprague–Dawley rats were randomly divided into three experimental groups: sham group (rats underwent bowel transection and re-anastomosis), SBS group (rats underwent 80% bowel resection), SBS-BSDL group (SBS rats orally administered BSDL). The animals were weighed daily. The intestinal morpho-histochemical changes and intestinal barrier function were determined 14 days after the operations. Meanwhile, the expressions of Wnt signaling molecules in enterocytes were also analyzed by immunohistochemistry and Western blot. The postoperative weight gain was faster in the SBS rats treated with BSDL than in the SBS/untreated group. The SBS rats treated with BSDL had significantly greater villus height, crypt depth, and enterocyte proliferation in their residual intestines, as compared with the SBS/untreated group. The recovery of intestinal barrier function was promoted and the expressions of tight-junction proteins were increased in the SBS rats treated with BSDL. Additionally, the data indicated that the proadaptive activities of BSDL might be mediated by Wnt signaling activation in the enterocytes. These observations suggested that enteral BSDL administration promoted intestinal adaptive growth and barrier repairing by activating Wnt signaling pathway in SBS rats.

The monitoring of children with cerebral palsy (CP) should include a precise assessment of the nutritional status to identify children and adolescents at risk of nutrition disorders. Available studies assessing the nutritional status of children with CP mainly focus on the relationship between body composition and the coexistence of motor dysfunctions, frequently overlooking the role of muscle tone. Therefore, the aim of this study was to assess the relationship between body composition and muscle tone in children with CP. In a case-control study (n = 118; mean age 11 y; SD = 3.8), the children with CP presented various stages of functional capacities, corresponding to all the levels in gross motor function classification system (GMFSC), and muscle tone described by all the grades in Ashworth scale. The control group consisted of healthy children and adolescents, strictly matched for gender and age in a 1:1 case-control manner. The children with CP were found with significantly lower mean values of fat-free mass (FFM kg = 29.2 vs. 34.5, p < 0.001), muscle mass (MM kg = 18.6 vs. 22.6, p < 0.001), body cell mass (BCM kg = 15.1 vs. 18.3, p < 0.001), and total body water (TBW L = 23.0 vs. 26.7, p < 0.001). The same differences in body composition were identified with respect to gender (p < 0.01 respectively). Moreover, children with higher muscle tone (higher score in Ashworth scale) were found with significantly lower values of fat mass (FM), FFM, MM, BCM, and TBW (p < 0.05). The findings showed lower parameters of body composition in the children with CP compared to the healthy children, and a decrease in the parameters coinciding with higher muscle tone in the study group. This observation suggests that it is necessary to measure muscle tone while assessing nutritional status of children with CP.

Total parenteral nutrition causes liver damage in patients with short bowel syndrome (SBS), in whom intestinal failure-associated liver disease (IFALD) is the strongest risk factor for mortality. We previously demonstrated the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4-Is) for nutritional absorption and intestinal barrier function enhancement. Herein, we investigated the efficacy of DPP4-Is in preventing liver damage in SBS rat models. Rats were allocated to one of five groups: normal saline (NS) + sham, DPP4-I + sham, NS + SBS, DPP4-I + SBS, and GLP-2 + SBS. DPP4-I or NS was administered orally once daily. Serum aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, and total bile acid levels were measured to assess liver function. Moreover, we evaluated liver damage using the SAF (steatosis activity fibrosis) score, which is also used to assess nonalcoholic steatohepatitis. ALT levels and SAF scores were significantly lower in the DPP4-I + SBS group than in the NS + SBS group. Jejunal and ileal villus heights were significantly higher in the DPP4-I + SBS group than in the GLP-2 + SBS group. The downregulation of ALT levels and SAF scores triggered by DPP4-I use may be correlated with DPP4-I-induced adiposis inhibition in SBS and NASH models. Therefore, DPP4-I may be used to reduce IFALD in patients with SBS.

The colon can have an absorptive function similar to that of the small intestine after the massive resection of the small bowel. To improve colonic absorptive function, we created a valve in the colon (artificial colonic valve, ACV). ACVs were created in 20 rats that had 80 percent of their small intestine resected, with an observation time of 30 weeks. The ACV rats were compared with those in the non-operated control group, the short bowel syndrome (SBS) group and the colon interposition (CI) group. The ACV rats were much heavier than those in the control group, SBS group and CI group. In terms of histology and the levels of α-amylase and the Na+-dependent bile salt transporter, the absorptive function of the colons before the valves resembled that of the small intestine. The colonic absorptive function was more obvious in ACV rats than in CI rats. An ACV can enhance colonic absorptive function after the massive resection of the small intestine. The colonic absorptive function of ACV rats was better than that of the rats in the CI group.

Sepsis is commonly associated with or complicates short bowel syndrome (SBS). The purpose of the present study was to investigate the effects of endotoxemia on intestinal adaptation in a rat model of SBS. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, SBS rats underwent 75% small bowel resection, and SBS-LPS rats underwent bowel resection and were given lipopolysaccharide. Bowel weight, organ weights, and parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth) were determined on day 15 following operation. The results of this study demonstrate that SBS rats showed a significant increase (vs. Sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. SBS-LPS animals demonstrated lower (vs. SBS rats) final body weight (215 +/- 7 vs. 287 +/- 10 g, P < 0.05), overall weight in duodenum (98+/- 2 vs. 119 +/-5 mg/cm, P < 0.05) and jejunum (144 +/- 9 vs. 189 +/- 16 mg/cm, P < 0.05), mucosal weight in jejunum (54 +/- 5 vs. 69 +/- 5 mg/cm, P < 0.05) and ileum (31 +/- 2 vs. 37 +/- 3 mg/cm, P < 0.05), mucosal DNA in jejunum (89 +/- 11 vs. 120 +/- 11 microg/cm, P < 0.05) and ileum (46 +/- 6 vs. 61 +/- 4 microg/cm, P < 0.05), jejunal crypt depth (152 +/- 19 vs. 189 +/- 12 microm, P < 0.05), and ileal villus height (405 +/- 63 vs. 515 +/- 30 pm, P < 0.05). In addition, the SBS group had no late (second week) mortality, whereas the SBS-LPS group had an 17% late mortality rate. In conclusion, in a rat model of SBS-LPS, endotoxemia appears to inhibit structural intestinal adaptation and increase mortality.

BackgroundThe milk fat globule membrane (MFGM), a tri-layer membrane structure surrounding the milk fat globule, has been shown to have immune-modulating properties. This study aimed to investigate the effects of MFGM supplementation in a rat model of short bowel syndrome (SBS) associated liver disease and its possible mechanisms.Materials and MethodsTwenty one male Sprague-Dawley rats were randomly divided into three groups: Sham, SBS (underwent massive small bowel resection), and SBS+MFGM (SBS rats supplemented with 1.5 g/kg/d MFGM). Liver pathology, myeloperoxidase (MPO) staining, serum levels of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), endotoxin concentration, protein expression of autophagy and nucleotide binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) pathway in the liver tissue were measured.ResultsBoth SBS and SBS + MFGM groups had higher serum levels of ALT and liver endotoxin levels than the Sham group (P < 0.05), with no difference detected between each other. Compared with the SBS group, the SBS+MFGM group showed lower liver pathology scores of steatosis and inflammation, less MPO positive cells and reduced expressions of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β(P < 0.05) in the liver. Additionally, the expression of Beclin-1 and microtubule-associated protein1 light chain 3(LC3) B, the fluorescence intensity of NLRP3 and LC3B in the SBS + MFGM group were lower than the SBS group (P < 0.05). The LC3B expression was positively correlated with the NLRP3 level.ConclusionEnteral supplementation of MFGM help to alleviate liver injury in SBS rats, which might be related to inhibition of aberrant activation of autophagy and NLRP3 inflammasome pathways.

Pediatric short bowel syndrome (SBS) is a rare condition characterized by a massive loss of the small intestine, leading to the inability to meet nutritional requirements without the use of parenteral or enteral supplementation. SBS causes profound alterations in the intestinal microbiome and metabolome. The aim of this study was a detailed assessment of the intestinal microbiome and metabolome in a murine model of SBS. We performed a 60% proximal small bowel resection versus a sham operation in C57BL/6 mice. Four weeks postoperatively, the microbial communities of different intestinal segments (jejunum, ileum, colon) and stool were assessed by 16S rRNA gene sequencing. Bile acids in serum and stool and volatile organic compounds (VOCs) in the fecal headspace were assessed using LC-MS and GC-MS techniques. The α-diversity of the different intestinal segments did not significantly differ between the two groups. β-diversity significantly differed between sham and SBS mice. While in the jejunum, Faecalibaculum was significantly increased in SBS animals, a significant reduction in Lactobacillus and Sporosarcina was detected in the ileum of SBS mice. In the colon of SBS mice, a significant decrease in Ruminococcaceae and a significant increase in Proteobacteria such as Faecalibaculum and Escherichia-Shigella were found. Serum levels of deoxycholic, taurocholic and taurochenodeoxycholic acids were significantly higher in the SBS group. Of the 29 VOCs tested, hexane, isoflurane and pentane were significantly higher in the SBS group, and pyrrole was significantly lower. We were able to show that SBS causes shifts in the murine intestinal microbiome and metabolome including serum BAs and fecal VOCs.

Decrease in hepatic circulation induces hepatic fibrosis in a neonatal piglet model with short bowel syndrome

The purpose of the present study was to evaluate the effects of exogenous bilirubin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into 5 experimental groups: Sham rats underwent bowel transection and reanastomosis, sham multiple doses of bilirubin (MDB) rats underwent bowel transection and were treated with bilirubin, SBS rats underwent a 75% small bowel resection, SBS-SDB (single dose bilirubin) rats underwent a bowel resection and were treated with a single dose of bilirubin, and SBS-MDB underwent a bowel resection and were treated with 3 doses of bilirubin. Bilirubin was administered intraperitoneally from the 7th day through the 14th day postoperatively. Serum total bilirubin concentration over time was evaluated in 5 SBS-SDB rats following a single intraperitoneal dose. Total bilirubin, alanine aminotransferase, and aspartate aminotransferase in serum and parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15. SBS-SDB and SBS-MDB animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth (vs SBS animals). Bilirubin-treated rats showed a lower apoptotic index in jejunum and ileum and a trend toward an increase in cell proliferation in jejunum and ileum (vs SBS group). In a rat model of SBS, exogenous bilirubin inhibits structural intestinal adaptation. Increased cell proliferation and decreased apoptosis may be considered adaptive mechanisms that maintain cell mass.

Background: The massive resection of the small intestine leading to short bowel syndrome (SBS) deprives an organism of many immunocompetent cells concentrated in gut-associated lymphoid tissue, the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, based on peripheral lymphocyte subsets and serum immunoglobulins. Methods: 15 children who underwent bowel resection in the first months of their life and required further home parenteral nutrition were enrolled into the study. Based on flow cytometry, the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+, and activated T cells. Results: Statistically significant differences were found for the rates of lymphocytes B, T, CD8+, and NK cells. The absolute count of NK cells was lower in the SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+, and percentages of lymphocytes CD4+, and activated T cells inversely correlated with age in SBS group. Conclusions: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time points out the necessity for longer follow- up.

Enteral Nutrition in the Management of Pediatric Intestinal Failure

Resting energy expenditure (REE) by indirect calorimetry and body composition by bioimpedance analysis are studied in three groups of children aged 5–18 years. Group 1 (n = 181) – patients in remission of cancer, group 2 (n = 55) – children with oncology diseases receiving chemotherapy or who are in the early period after hematopoietic stem cell transplantation, group 3 (n = 63) – children with non-malignant diseases of the gastrointestinal tract. To eliminate the influence of age and gender on the intergroup comparisons, body composition parameters were expressed as standardized values (z-scores) relative to a reference group of healthy Russian children (n = 138,191). Group 1 was characterized by excess fat content with intact lean body mass, and groups 2 and 3 by protein depletion, more pronounced in Group 2 with a higher percentage of body fat. All used conventional formulas (WHO, Harris–Benedict and others) in groups 1 and 3 underestimated REE as compared with indirect calorimetry. A new formula for REE, giving an unbiased estimate in the group 1 was proposed: REE (kcal/day) = 28.7 × BCM (kg) +10.5 × Height (cm) – 38.6 × Age (years) – 134, where BCM – body cell mass according to bioimpedance analysis (R2 = 0.67, the standard deviation of 196 kcal/day).

Ultra-short bowel syndrome (USBS) constitutes the most severe form of short bowel syndrome (SBS). Contemporary outcome data are scarce. The aim was to describe the experience of managing children with USBS and assess outcomes. This retrospective study analyzed children with intestinal failure (IF) managed at a single center between 2018 and 2022. Patients with USBS were matched to SBS controls by age and sex. Demographics and medical history were retrieved. Primary outcomes focused on long-term complications, including cholestasis, central line-associated bloodstream infections (CLABSI), mortality, oral aversion, and vitamin deficiencies. The cohort included 28 children (median age: 44.4 months), 14 with USBS. Compared to SBS, children with USBS had significantly shorter small bowel lengths (percentage of remaining bowel length 6 (4, 8) vs. 25 (18, 29), p < 0.001) and reduced large bowel percentages (58% vs. 100%, p < 0.01). At data collection, 93% of USBS patients required PN, compared to 30% with SBS. Despite longer PN dependency, rates of cholestasis and CLABSI were similar. Oral aversion was more prevalent in USBS (71% vs. 21%, p < 0.001). High rates of vitamin B12 and iron deficiencies were observed in both groups. No mortality was recorded, and one USBS patient achieved enteral autonomy. When compared with SBS, children with USBS exhibited greater PN dependency but similar rates of major IF-related complications. These findings highlight that even among children with USBS and intestinal failure, long-term outcomes can be favorable under specialized care.