Chyme Reinfusion Restores the Regulatory Bile Salt-FGF19 Axis in Patients With Intestinal Failure.

BACKGROUND AND AIMS: Automated chyme reinfusion (CR) in patients with intestinal failure (IF) and a temporary double enterostomy (TDE) restores intestinal function and protects against liver injury, but the mechanisms are incompletely understood. The aim was to investigate whether the beneficial effects of CR relate to functional recovery of enterohepatic signaling through the bile salt-FGF19 axis. APPROACH AND RESULTS: Blood samples were collected from 12 patients, 3 days before, at start, and 1, 3, 5, and 7 weeks after CR initiation. Plasma FGF19, total bile salts (TBS), 7-α-hydroxy-4-cholesten-3-one (C4; a marker of bile salt synthesis), citrulline (CIT), bile salt composition, liver tests, and nutritional risk indices were determined. Paired small bowel biopsies prior to CR and after 21 days were taken, and genes related to bile salt homeostasis and enterocyte function were assessed. CR induced an increase in plasma FGF19 and decreased C4 levels, indicating restored regulation of bile salt synthesis through endocrine FGF19 action. TBS remained unaltered during CR. Intestinal farnesoid X receptor was up-regulated after 21 days of CR. Secondary and deconjugated bile salt fractions were increased after CR, reflecting restored microbial metabolism of host bile salts. Furthermore, CIT and albumin levels gradually rose after CR, while abnormal serum liver tests normalized after CR, indicating restored intestinal function, improved nutritional status, and amelioration of liver injury. CR increased gene transcripts related to enterocyte number, carbohydrate handling, and bile salt homeostasis. Finally, the reciprocal FGF19/C4 response after 7 days predicted the plasma CIT time course. CONCLUSIONS: CR in patients with IF-TDE restored bile salt-FGF19 signaling and improved gut-liver function. Beneficial effects of CR are partly mediated by recovery of the bile salt-FGF19 axis and subsequent homeostatic regulation of bile salt synthesis.

COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure.

BACKGROUND AND AIMS: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: Period of observation: March 1st, 2020 March 1st, 2021. INCLUSION CRITERIA: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. RESULTS: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. CONCLUSIONS: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.

Hydration by colonic enteroclysis: An alternative to parenteral hydration in patients with high-output double enterostomy.

BACKGROUND: High-output double enterostomies (DESs) result in sodium and fluid loss responsible for frequent episodes of dehydration and hospitalizations. Hydration by enteroclysis (HE) is an alternative to parenteral hydration when the small bowel, or the downstream colon, is accessible and functional. METHODS: A retrospective analysis was conducted on all consecutive patients admitted in our institution with high-output (≥1200 ml per 24 h) DES and access to downstream intestine (including colon), who were treated by enteroclysis between 2015 and 2019. A sodium chloride and bicarbonate solution was instilled through a tube inserted in the colon. The objectives were diuresis >1 L, natriuresis >40 mmol/24 h, and urinary sodium-to-potassium ratio >1. RESULTS: HE was conducted in 52 patients (24 female, 28 male). Initially, 30 patients received intravenous support. Fifteen patients (50%) were weaned from all parenteral support, of whom 11 of 12 (92%) received fluid and electrolyte support and 4 of 18 (22%) received parenteral nutrition (PN). When intravenous fluids were still required, daily volumes decreased from 2714 ± 1424 to 1578 ± 1000 ml per 24 h (P = .001), as did the energetic intake (NS), from 1439 ± 556 to 1230 ± 362 kcal per 24 h (P = .096). CONCLUSION: HE through the efferent intestine limits the requirement for parenteral hydration in patients with high-output DES. For patients with intestinal failure dependent on PN, it reduces daily infused volumes.

Management of Central Venous Catheters in Children and Adults on Home Parenteral Nutrition: A French Survey of Current Practice.

Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.

Removal of transanastomotic pancreatic stent tubes after pancreaticoduodenectomy: a new role for double-balloon enteroscopy.

BACKGROUND: Endoscopic interventions are usually very challenging in patients with anatomic changes caused by earlier GI surgery. The recent development of the double-balloon enteroscopy (DBE) system creates an opportunity to reach the biliary tract and the pancreatic duct in postsurgical conditions. OBJECTIVE: To report a further application of DBE in surgical patients; namely, extraction of pancreatic stents placed in pancreaticojejunal anastomosis during pancreaticoduodenectomy. DESIGN: Two case reports. SETTING: A single-center experience in a tertiary-care unit. PATIENTS AND INTERVENTIONS: Two patients who underwent Whipple resection with Roux-en-Y reconstruction presented with migration of pancreatic stent tubes inserted in pancreaticojejunal anastomoses. Stents had migrated to the end of the afferent limb and were causing abdominal pain. Because extraction failed by using conventional endoscopy, we used the DBE system. MAIN OUTCOME MEASURES: Successful extraction of the stents. RESULTS: Stents were successfully removed in both patients with no complications. After 1 year of follow-up, the patients remained free of painful symptoms. LIMITATIONS: Small volume case series. CONCLUSIONS: Double-balloon enteroscopy is a reliable way to investigate and treat patients with postsurgical altered anatomy. Here, we report the successful removal of pancreatic stents migrating into the jejunal loop through pancreaticojejunal anastomosis.

Chyme Reinfusion in Intestinal Failure Related to Temporary Double Enterostomies and Enteroatmospheric Fistulas.

Some temporary double enterostomies (DES) or entero-atmospheric fistulas (EAF) have high output and are responsible for Type 2 intestinal failure. Intravenous supplementations (IVS) for parenteral nutrition and hydration compensate for intestinal losses. Chyme reinfusion (CR) artificially restores continuity pending surgical closure. CR treats intestinal failure and is recommended by European Society for Clinical Nutrition and Metabolism (ESPEN) and American Society for Parenteral and Enteral Nutrition (ASPEN) when possible. The objective of this study was to show changes in nutritional status, intestinal function, liver tests, IVS needs during CR, and the feasibility of continuing it at home. A retrospective study of 306 admitted patients treated with CR from 2000 to 2018 was conducted. CR was permanent such that a peristaltic pump sucked the upstream chyme and reinfused it immediately in a tube inserted into the downstream intestine. Weight, plasma albumin, daily volumes of intestinal and fecal losses, intestinal nitrogen, and lipid absorption coefficients, plasma citrulline, liver tests, and calculated indices were compared before and during CR in patients who had both measurements. The patients included 185 males and 121 females and were 63 ± 15 years old. There were 37 (12%), 269 (88%) patients with EAF and DES, respectively. The proximal small bowel length from the duodeno-jejunal angle was 108 ± 67 cm (n = 232), and the length of distal small intestine was 117 ± 72 cm (n = 253). The median CR start was 5 d (quartile 25-75%, 2-10) after admission and continued for 64 d (45-95), including 81 patients at home for 47 d (28-74). Oral feeding was exclusive 171(56%), with enteral supplement 122 (42%), or with IVS 23 (7%). Before CR, 211 (69%) patients had IVS for nutrition (77%) or for hydration (23%). IVS were stopped in 188 (89%) 2 d (0-7) after the beginning of CR and continued in 23 (11%) with lower volumes. Nutritional status improved with respect to weight gain (+3.5 ± 8.4%) and albumin (+5.4 ± 5.8 g/L). Intestinal failure was cured in the majority of cases as evidenced by the decrease in intestinal losses by 2096 ± 959 mL/d, the increase in absorption of nitrogen 32 ± 20%, of lipids 43 ± 30%, and the improvement of citrulline 13.1 ± 8.1 µmol/L. The citrulline increase was correlated with the length of the distal intestine. The number of patients with at least one liver test >2N decreased from 84-40%. In cases of Type 2 intestinal failure related to DES or FAE with an accessible and functional distal small bowel segment, CR restored intestinal functions, reduced the need of IVS by 89% and helped improve nutritional status and liver tests. There were no vital complications or infectious diarrhea described to date. CR can become the first-line treatment for intestinal failure related to double enterostomy and high output fistulas.

Management of entero-atmospheric fistulas by chyme reinfusion: A retrospective study.

BACKGROUND & AIMS: High output entero-cutaneous fistulas may lead to intestinal failure with parenteral nutrition (PN) as the gold standard treatment to prevent dehydration and malnutrition. However in case of entero-atmospheric fistula (EAF) with the distal limb of the fistula accessible, chyme reinfusion (CR), a technique that restores artificially digestive continuity can be performed until the surgical repair. Our aim was to study the efficacy of CR in EAF regarding nutritional status, intestinal function, PN weaning and liver tests. METHODS: Retrospective study of 37 patients admitted for EAF and treated by CR from 1993 to 2017. Delays were expressed in median (25%-75% quartiles) and other data on mean ± SD. RESULTS: Location of EAF: jejunum (29), ileum (8). The length of the upstream intestine was estimated in 21 patients: 19 had a bowel length <150 cm of which 16 had less than 100 cm. During CR, mean digestive losses decreased from 1734 ± 578 to 443 ± 487 ml/24 h (p < 0.000001), nitrogen absorption increased from 45.3 ± 18.6 to 81.8 ± 12.9% of ingesta (p < 0.001). The percentage of patients with plasma citrulline <20 µmol/l decreased from 71 to 10%. PN was stopped in all patients within 3 (0-14) days after CR initiation, 2 patients required an intravenous hydration and 20 had an additional enteral support. The nutritional status improved: albumin (33.1 ± 5.1 g/L vs 28.4 ± 6.5, p < 0.001), NRI (decrease of the number of patients at risk of severe malnutrition from 22 to 10 (p < 0.001)). The number of patients who had one or several liver tests abnormalities (>2 N) decreased from 94 to 41% (p < 0.001). CONCLUSION: When the efferent part of the small bowel is accessible, CR is a safe and inexpensive method that restores bowel function. In most cases, it makes it possible to stop PN and helps to improve the nutritional status until surgical reconstruction.

Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome: A pilot, randomized, double-blind, cross-over study.

BACKGROUND & AIMS: As citrulline is produced by small intestine, plasma citrulline concentration is decreased and may become essential in patients with short bowel syndrome (SBS). In a rat model of SBS, citrulline supplementation enhanced muscle protein synthesis. The aim of the study was to determine whether citrulline impacts whole body protein metabolism in patients with SBS. METHODS: Nine adults with non-malignant SBS (residual small bowel 90 ± 48 cm; mean ± SD) who were in near-normal nutritional status without any artificial nutrition, were recruited long after surgery. They received 7-day oral supplementation with citrulline (0.18 g/kg/day), or an iso-nitrogenous placebo in a randomized, double-blind, cross-over design with a 13-day wash-out between regimens, and an intravenous 5-h infusion of L-[1-13C]-leucine in the postabsorptive state to assess protein metabolism after each regimen. RESULTS: Plasma citrulline concentration rose 17-fold (25 ± 9 vs. 384 ± 95 µmol/L) and plasma arginine 3-fold after oral citrulline supplementation (both p < 4 × 10-6). Supplementation did not alter leucine appearance rate (97 ± 5 vs. 97 ± 5 µmol kg-1.h-1; p = 0.88), leucine oxidation (14 ± 1 vs. 12 ± 1 µmol kg-1.h-1; p = 0.22), or non-oxidative leucine disposal (NOLD), an index of whole-body protein synthesis (83 ± 4 vs. 85 ± 5 µmol kg-1.h-1; p = 0.36), nor insulin or IGF-1 plasma concentrations. In each of the 3 patients with baseline citrulline<20 µmol/L, citrulline supplementation increased NOLD. Among the 7 patients with plasma citrulline <30 µmol/L, the effect of supplementation on NOLD correlated inversely (r2 = 0.81) with baseline plasma citrulline concentration. CONCLUSION: 1) Oral citrulline supplementation enhances citrulline and arginine bioavailability in SBS patients. 2) Oral citrulline supplementation does not have any anabolic effect on whole body protein metabolism in patients with SBS in good nutritional status, in the late phase of intestinal adaptation, and with near-normal baseline citrulline homeostasis. 3) Whether oral citrulline would impact whole body protein anabolism in severely malnourished SBS patients in the early adaptive period, and with baseline plasma citrulline below 20 µmol/L, warrants further study. Registered under ClinicalTrials.gov Identifier no. NCT01386034.

Chyme reinfusion in patients with intestinal failure due to temporary double enterostomy: A 15-year prospective cohort in a referral centre.

BACKGROUND & AIMS: Patients with double temporary enterostomy may suffer from intestinal failure (IF). Parenteral nutrition (PN) is the gold standard treatment until surgical reestablishment of intestinal continuity. Chyme reinfusion (CR) is a technique consisting in an extracorporeal circulation of the chyme. The aims were to determine: i) whether CR could restore intestinal absorption, decrease PN needs, improve nutritional status and plasma liver tests; ii) the feasibility of home CR. METHODS: From the 232 patients IF consecutively referred for CR from 2000 to 2014, the 212 patients with IF, technical feasibility of CR, and effectively treated by CR, were included. Were collected prospectively before and during CR: daily stomal and fecal outputs, coefficients of nitrogen (CNDA) and fat (CFDA) digestive absorption, weight loss, body mass index (BMI), Nutritional Risk Index (NRI), plasma albumin, citrulline, and liver tests. RESULTS: 183 patients had temporary double enterostomy and 29 exposed enterocutaneous fistulas. CR reduced the intestinal output (2444 ± 933 vs 370 ± 457 ml/day, P < 0.001), improved CNDA (46 ± 16 vs 80 ± 14%, P < 0.001) and CFDA (48 ± 25 vs 86 ± 11%, P < 0.001), and normalized plasma citrulline concentration (17.6 ± 8.4 vs 30.3 ± 11.8 µmol/l, P < 0.001). PN was stopped in 126/139 (91%) patients within 2 ± 8 d. Nutritional status improved (P < 0.001): weight (+4.6 ± 8.6%), BMI (+3.8 ± 7.7%), plasma albumin (+6.2 ± 6.1 g/l), and NRI (+10.9 ± 9.5). The proportion of patients with plasma liver tests abnormalities decreased (88 vs 51%, P < 0.01). Home CR was feasible without any serious complications in selected patients. CONCLUSIONS: CR corrected the intestinal failure by restoring intestinal absorption, allowing PN weaning in 91% of patients. CR contributes to improve nutritional status and to reduce plasma liver tests abnormalities, and is feasible at home.

Increased intestinal absorption by segmental reversal of the small bowel in adult patients with short-bowel syndrome: a case-control study.

BACKGROUND: Segmental reversal of the small bowel (SRSB) is proposed in patients with short-bowel syndrome (SBS) as a rehabilitative therapy, but its effects on absorption have not been studied. OBJECTIVE: We aimed to determine intestinal macronutrient absorption and home parenteral nutrition (HPN) dependence in SBS patients with intestinal failure. DESIGN: We included in a retrospective study all consecutive patients who had an SRSB between 1985 and 2010 and underwent a study of macronutrient absorption. Patients were matched to SBS controls with the same digestive characteristics. Energy and macronutrient absorption were measured. The dependence on HPN was expressed by the number of infusions per week and by the calories infused daily divided by the basal energy expenditure multiplied by 1.5. RESULTS: Seventeen patients who had an SRSB were matched to 17 control patients. Intestinal absorption was higher in the SRSB group for total calories (69.5% compared with 58.0%), fat (48.4% compared with 33.2%), and protein (62.7% compared with 53.4%) (P < 0.05). Median oral autonomy was 100% ± 38.4% in the SRSB group, whereas it was 79% ± 39.6% in the control group (P < 0.05). The number of calories infused was lower in the SRSB group (500 ± 283 compared with 684 ± 541; P < 0.05), as was HPN dependence (33% ± 20% compared with 48% ± 38%; P < 0.05) at the time of the study. CONCLUSION: SRSB allows a gain in macronutrient absorption, which is associated with a lower HPN dependence. To our view, SRSB should be integrated in intestinal rehabilitative adult programs.

Changes in brain activity after a diet-induced obesity.

Compared to lean subjects, obese men have less activation in the dorsolateral prefrontal cortex, a brain area implicated in the inhibition of inappropriate behavior, satiety, and meal termination. Whether this deficit precedes weight gain or is an acquired feature of obesity remains unknown. An adult animal model of obesity may provide insight to this question since brain imaging can be performed in lean vs. obese conditions in a controlled study. Seven diet-induced obese adult minipigs were compared to nine lean adult minipigs housed in the same conditions. Brain activation after an overnight fasting was mapped in lean and obese subjects by single photon emission computed tomography. Cerebral blood flow, a marker of brain activity, was measured in isoflurane-anesthetized animals after the intravenous injection of 99mTc-HMPAO (750 MBq). Statistical analysis was performed using statistical parametric mapping (SPM) software and cerebral blood flow differences were determined using co-registered T1 magnetic resonance imaging (MRI) and histological atlases. Deactivations were observed in the dorsolateral and anterior prefrontal cortices in obese compared to lean subjects. They were also observed in several other structures, including the ventral tegmental area, the nucleus accumbens, and nucleus pontis. On the contrary, activations were found in four different regions, including the ventral posterior nucleus of the thalamus and middle temporal gyrus. Moreover, the anterior and dorsolateral prefrontal cortices as well as the insular cortex activity was negatively associated with the body weight. We suggested that the reduced activation of prefrontal cortex observed in obese humans is probably an acquired feature of obesity since it is also found in minipigs with a diet-induced obesity.