Intestinal adaptation and rehabilitation in adults with short bowel syndrome.

PURPOSE OF REVIEW: Over the past decade, trophic gastrointestinal hormonal factors have been included in the intestinal rehabilitation programs for short bowel syndrome (SBS). Up today the only trophic factor approved for clinical practice is the glucagon-like peptide-2 (GLP-2) analogue, teduglutide. A literature review on the last 2-year data on GLP-2 analogues for the treatment of SBS in adults has been performed. RECENT FINDINGS: Several reports on real-world data on the efficacy and safety of teduglutide treatment for SBS, some case-reports on the use of teduglutide in non-SBS conditions as well as phase 2 trials on new GL-2 analogues on patients with SBS have been retrieved. SUMMARY: Real-world data confirmed the teduglutide efficacy not only in weaning off IVS in accurately selected patients but also increased the alert on the risk of development of gastrointestinal polyps related to the drug; the impact of the therapy on patients' QoL deserves further studies and the cost-utility of the treatment is still uncertain. Some case reports highlighted the potential benefit of treatment with teduglutide in non-SBS gastrointestinal diseases, such as graft-versus-host disease, primary amyloidosis and refractory microscopic colitis. Phase 2 RCTs on safety and efficacy of two new long-acting GLP-2 analogues, glepaglutide and apraglutide, were published, and phase 3 RCTs have been completed.

Liraglutide 3.0 mg and mental health: can psychiatric symptoms be associated to adherence to therapy? Insights from a clinical audit.

INTRODUCTION: Liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) analogue, is a medication approved for obesity treatment. This study aimed to investigate the relationship between psychiatric symptoms, including depression, anxiety, and binge eating, and their impact on therapy adherence. METHODS: A clinical audit was carried out on a cohort of 54 adults with obesity treated with liraglutide 3.0 mg. We retrospectively analyzed the connection between psychiatric symptoms assessed through the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Binge Eating Scale (BES). Adherence to therapy was assessed by the maximum dosage (MD) and treatment duration (TD). RESULTS: Notably, a discontinuation rate of 59% was encountered. However, among those who continued the treatment, we observed a negative association between anxiety symptoms (STAI score) and MD, depression symptoms (BDI score) and TD, and a higher likelihood of binge eating (BES score > 17) and TD. Moreover, presence of psychiatric symptoms did not compromise drug's effectiveness in achieving weight loss, which was 4.43% (± 5.5 SD) in the whole sample and 5.3% (± 6.3 SD) in the subgroup evaluated at 12 weeks. CONCLUSION: We observed a high discontinuation rate in real-life clinical setting, where Liraglutide 3.0 therapy is paid out-of-pocket. While psychiatric symptoms might play a role in diminishing adherence to therapy, they do not prevent drug's effectiveness to promote weight loss. This finding underscores the potential advantages of liraglutide 3.0 mg therapy for individuals contending with obesity while simultaneously managing mental health challenges. LEVEL OF EVIDENCE: Level V, descriptive studies.

Risk of binge eating disorder in patients with metabolic dysfunction-associated steatotic liver disease.

PURPOSE: Very few data exist on the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and eating disorders. The study aimed to evaluate the presence of binge eating disorder (BED), in MASLD subjects. METHODS: Demographic, clinical investigation, anthropometric measurements and laboratory were collected in 129 patients with MASLD (34.1% males; age, 53.7 years; BMI, 34.4 kg/m2) addressed by general practitioners to a hospital-based unit of metabolic disorders. The risk of binge eating was tested by the binge eating scale (BES); values in the range 17-26 were considered "possible" BED, values > 26 were considered "probable" BED. Hepatic steatosis and fibrosis were tested by surrogate biomarkers and imaging (transient elastography). Calorie intake and lifestyle were self-assessed by questionnaires. RESULTS: Possible BED was present in 17.8% of cases, probable BED in another 7.6%, and were neither associated with gender, obesity class, diabetes, features of metabolic syndrome, nor with presence and severity of hepatic steatosis and fibrosis. Also steatosis grade by CAP and fibrosis stage by liver stiffness did not correlate with BES. However, an association was present between the daily caloric intake and "possible" BED (odds ratio, 1.14; 95% confidence interval, 1.05-1.24; "probable" BED, 1.21; 1.07-1.37), after adjustment for confounders. CONCLUSION: Binge eating, as scored by BES, is present in a significant proportion of MASLD cases screened for metabolic disorders in a specialized center. It may impact behavioral treatment, reducing the chance of weight loss without systematic psychological support. LEVEL OF EVIDENCE: Level III, cohort analytic study.

Value of immunonutrition in patients undergoing pancreatic resection: a trial sequential meta-analysis.

BACKGROUND: The benefits of immunonutrition (IM) in patients who underwent pancreatic surgery are unclear. METHODS: A meta-analysis of randomized clinical trials (RCTs) comparing IM with standard nutrition (SN) in pancreatic surgery was carried out. A random-effects trial sequential meta-analysis was made, reporting Risk Ratio (RR), mean difference (MD), and required information size (RIS). If RIS was reached, false negative (type II error) and positive results (type I error) could be excluded. The endpoints were morbidity, mortality, infectious complication, postoperative pancreatic fistula (POPF) rates, and length of stay (LOS). RESULTS: The meta-analysis includes 6 RCTs and 477 patients. Morbidity (RR 0.77; 0.26 to 2.25), mortality (RR 0.90; 0.76 to 1.07), and POPF rates were similar. The RISs were 17,316, 7,417, and 464,006, suggesting a type II error. Infectious complications were lower in the IM group, with a RR of 0.54 (0.36-0.79; 95 CI). The LOS was shorter in IM (MD -0.3 days; -0.6 to -0.1). For both, the RISs were reached, excluding type I error. CONCLUSION: The IM can reduce infectious complications and LOS The small differences in mortality, morbidity, and POPF make it impossible to exclude type II error due to large RISs.

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant.

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.

Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from patients with MNGIE. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron-specific enolase was used to label enteric neurons. Compared with controls, patients with MNGIE showed a decreased area of vascular tissue, but a twofold increase of submucosal vessels/mm2 with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index, and HIF-1α protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased interganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of patients with MNGIE. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown, and ischemic abnormalities in MNGIE.NEW & NOTEWORTHY Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by a genetically driven defect of thymidine phosphorylase, a multitask enzyme playing a role also in angiogenesis. Indeed, major gastrointestinal bleedings are life-threatening complications of MNGIE. Thus, we focused on jejunal submucosal vasculature and showed intestinal microangiopathy as a novel feature occurring in this disease. Notably, vascular changes were associated with neuromuscular abnormalities, which may explain gut dysfunction and help to develop future therapeutic approaches in MNGIE.

Effects of antidiabetic agents on steatosis and fibrosis biomarkers in type 2 diabetes: A real-world data analysis.

BACKGROUND & AIMS: There is intense research for drugs able to reduce disease progression in nonalcoholic fatty liver disease. We aimed to test the impact of novel antidiabetic drugs (dipeptidyl-peptidase-4 inhibitors - DPP-4Is, glucagon-like peptide-1 receptor agonists - GLP-1RAs, sodium-glucose cotransporter-2 inhibitors - SGLT-2Is) on non-invasive biomarkers of steatosis (fatty liver index, FLI) and fibrosis (Fibrosis-4 score, FIB-4) in patients with type 2 diabetes (T2D). METHODS: Clinical, anthropometric and biochemical parameters were retrospectively analysed in 637 consecutive T2D patients switched from metformin w/wo sulfonylureas and/or pioglitazone to DPP-4Is, GLP-1RAs and SGLT-2Is in a tertiary care setting. 165 patients maintained on original treatments served as controls. The effects on FLI and FIB-4 at 6- and 12-month follow-up were analysed by logistic regression after adjustment for baseline differences, computed by propensity scores, and additional adjustment for changes in glycosylated hemoglobin (HbA1c) and body mass index. RESULTS: Body mass index, HbA1c and aminotrasferases significantly decreased following switching to GLP-1RAs and SGLT2-Is, compared with both controls and DPP-4Is, whereas only HbA1c was reduced on DPP-4Is. FLI and FIB-4 were reduced on GLP-1RA and SGLT-2I; logistic regression analysis confirmed a significant improvement of both biomarkers after adjustment for propensity score. The shift of FIB-4 values towards the category ruling out advanced fibrosis was maintained after additional adjustment for confounders. These effects were confirmed in a sensitivity analysis on effect size. CONCLUSIONS: Glucagon-like peptide-1 receptor agonists and SGLT-2Is improve biomarkers of steatosis and fibrosis, in keeping with beneficial effects on liver disease progression, and should be considered the treatment of choice in T2D.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow-up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence-based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence-based guidance for clinicians incorporating patients' values and preferences.

NEUROD1 mutation in an Italian patient with maturity onset diabetes of the young 6: a case report.

BACKGROUND: Maturity Onset Diabetes of the Young (MODY) is a monogenic, autosomal, dominant disease that results in beta-cells dysfunction with consequent hyperglycaemia. It represents a rare form of diabetes (1-2% of all the cases). Sulphonylureas (SUs) represent the first-line treatment for this form of diabetes mellitus. NEUROD1 is expressed by the nervous and the pancreatic tissues, and it is necessary for the proper development of beta cells. A neurogenic differentiation factor 1 (NEUROD1) gene mutation causes beta-cells dysfunction, inadequate insulin secretion, and hyperglycaemia (MODY 6). CASE PRESENTATION: We have documented a new missense mutation (p.Met114Leu c.340A > C) of the NEUROD1 gene, pathogenetic for diabetes mellitus, in a 48 years-old man affected by diabetes since the age of 25 and treated with insulin basal-bolus therapy. Unfortunately, an attempt to replace rapid insulin with dapagliflozin has failed. However, after the genetic diagnosis of MODY6 and treatment with SUs, he was otherwise able to suspend rapid insulin and close glucose monitoring. Interestingly, our patient had an early onset dilated cardiomyopathy, though no data about cardiac diseases in patients with MODY 6 are available. CONCLUSIONS: Diagnostic criteria for MODY can overlap with other kinds of diabetes and most cases of genetic diabetes are still misdiagnosed as diabetes type 1 or 2. We encourage to suspect this disease in patients with a strong family history of diabetes, normal BMI, early-onset, and no autoimmunity. The appropriate therapy simplifies disease management and improves the quality of the patient's life.

Roles and competencies in the nutritional domain for the management of the metabolic diseases and in the hospital setting: A position paper of the Italian College of Academic Nutritionists, MED-49 (ICAN-49).

Epidemiological evidence has confirmed the potential causal relationship between specific dietary factors and non-communicable diseases. However, currently nutrition was shown to be insufficiently integrated into medical education, regardless of the country. Without an adequate nutrition education, it is reasonable to assume that future physicians, as well as other health care professionals, will be not able to provide the highest quality care to patients in preventing and treating non-communicable diseases. Furthermore, the insufficient availability of physicians with specializations in nutrition has posed the basis for the development of non-medical careers in the field of nutrition. The present document was drafting by the Italian College of Academic Nutritionists, MED-49 (ICAN-49), with the aim to provide an overview on the nutritional competency standards covered by several health care professionals (Physicians Clinical Nutrition Specialists, Clinical Dietitians, Professional Clinical Nutrition Specialists, etc) for the prevention of diseases and/or support of pharmacological therapies. The aim of the ICAN 49 is to suggest a major shift in practice opportunities and roles for many nutritionists, especially for the management of the metabolic diseases, and promote a paradigm change: a clinical and educational leadership role for Physician Clinical Nutrition Specialists in the hospital setting.

New insights into the indications for intestinal transplantation.

PURPOSE OF REVIEW: To discuss the new guidelines on the indications for intestinal transplantation (ITx) devised in 2019 by the Intestinal Rehabilitation and Transplant Association. RECENT FINDINGS: Early referral of patients with intestinal failure to expert intestinal rehabilitation/transplant centre is strongly recommended. Listing for a life-saving transplantation is recommended for intestinal failure-associated liver disease (IFALD) evolving to liver failure, invasive intra-abdominal desmoids, acute diffuse intestinal infarction with hepatic failure, re-transplant, and children with loss of at least three of the four upper central venous access sites or with high morbidity intestinal failure. Developments in ITx made the probability of posttransplant survival equal to that on home parenteral nutrition (HPN) and the QoL after successful ITx better than on HPN. However, for patients who have not an actual increased risk of death on HPN, the matter of preemptive listing for ITx is still controversial. For these patients, a careful case-by-case decision is recommended. SUMMARY: The new guidelines on ITx confirm the straight referral for ITx only for patients at actual risk of death on HPN. Improvements in ITx practice and results, advances in the severity classification of intestinal failure, monitoring of the evolution of IFALD, and measuring patients' QoL are required for an immediate progression in the treatment of intestinal failure.

Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure.

BACKGROUND AND AIM: No marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity. METHODS: At baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as <1, 1-2, 2-3 and >3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI). RESULTS: Fifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN <1 L/day than for FE and all PN >1 L/day), patients' death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2-3 and PN >3 L/day). CONCLUSIONS: The type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.

Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal, recessive disease caused by mutations in the gene encoding thymidine phosphorylase, leading to reduced enzymatic activity, toxic nucleoside accumulation, and secondary mitochondrial DNA damage. Thymidine phosphorylase replacement has been achieved by allogeneic hematopoietic stem cell transplantation, a procedure hampered by high mortality. Based on high thymidine phosphorylase expression in the liver, a 25-year-old severely affected patient underwent liver transplantation. Serum levels of toxic nucleosides rapidly normalized. At 400 days of follow-up, the patient's clinical conditions are stable. We propose liver transplantation as a new therapy for MNGIE. Ann Neurol 2016;80:448-455.

ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro-intestinal encephalomyopathy.

Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly.

Iodine status in intestinal failure in adults.

PURPOSE OF REVIEW: The aim of this work is to review the recent findings on iodine nutrition in adults with intestinal failure. RECENT FINDINGS: Patients with intestinal failure who require long-term parenteral nutrition are potentially at risk for trace element deficiencies. It was considered that iodine deficiency was unlikely to occur in adults on parenteral nutrition, even if iodine is not added to parenteral nutrition, because of iodine absorption from iodine-containing antiseptics, to presence of iodine as contaminant in parenteral nutrition products and to absorption of dietary iodine, in patients eating and having a functioning duodenum. It is believed that thyroidal iodine could support thyroid function for several months during total parenteral nutrition. Clinical Nutrition Societies do not have uniform opinion about the need to supplement iodine routinely in parenteral nutrition in adults. Although very few studies have addressed this topic, inadequate iodine supply in long-term parenteral nutrition in young adults, and the increased risk of iodine deficiency in adults on long-term parenteral nutrition have recently been reported. SUMMARY: There is some evidence that adults with intestinal failure on long-term parenteral nutrition may be at risk of iodine deficiency. Studies carried out in large cohorts of patients are required to better define iodine requirements in long-term parenteral nutrition.

Plasma citrulline after small bowel transplantation: effect of time from transplantation, acute cellular rejection, and renal failure.

BACKGROUND: Plasma citrulline concentration (CIT) depends on its synthesis by enterocytes and its catabolism by renal tubules. To evaluate CIT applicability as a marker of acute cellular rejection (ACR) after intestinal transplantation (ITx), CIT was investigated according to time from ITx, episodes of ACR, and creatinine clearance (CrCl). METHODS: Twenty-four adult ITx recipients were prospectively studied. The results were compared with those of 19 healthy controls (HCs) and of 29 patients with chronic renal failure (CRF). RESULTS: In ITx recipients, CIT was lower than in HCs during the first two postoperative weeks; it then progressively increased and reached the range observed in HCs, approximately between the 31st and the 45th postoperative day. A positive association with postoperative days (R = 0.63; p < 0.0001) and a negative association with CrCl (R = -0.57; p < 0.0001) were observed. CIT was higher in patients with CRF than in HCs (p < 0.0001). CIT sensitivity and specificity in detecting ACR after the 45th postoperative day were 38% and 83%, using CIT threshold observed in HCs, and 69% and 77%, respectively, using CIT threshold adjusted for CRF degree. CONCLUSIONS: Adjusting CIT threshold for CRF degree almost doubled the sensitivity of CIT as a non-invasive marker of ACR in ITx recipients.

Use of teduglutide in adults with short bowel syndrome-associated intestinal failure.

Short bowel syndrome (SBS) is a rare gastrointestinal disorder associated with intestinal failure (SBS-IF) and poor health-related outcomes. Patients with SBS-IF are unable to absorb sufficient nutrients or fluids to maintain significantly metabolic homeostasis via oral or enteral intake alone and require long-term intravenous supplementation (IVS), consisting of partial or total parenteral nutrition, fluids, electrolytes, or a combination of these. The goal of medical and surgical treatment for patients with SBS-IF is to maximize intestinal remnant absorptive capacity so that the need for IVS support may eventually be reduced or eliminated. Daily subcutaneous administration of the glucagon-like peptide 2 analog, teduglutide, has been shown to be clinically effective in reducing IVS dependence and potentially improving the health-related quality of life of patients with SBS-IF. The management of patients with SBS-IF is complex and requires close monitoring. This narrative review discusses the use of teduglutide for patients with SBS-IF in clinical practice. The screening of patient eligibility for teduglutide treatment, initiation, monitoring of efficacy and safety of treatment, adapting or weaning off IVS, and the healthcare setting needed for SBS-IF management are described, taking into consideration data from clinical trials, observational studies, and clinical experience.

The gut microbiota in adults with chronic intestinal failure.

OBJECTIVE: Fecal microbiota was investigated in adult patients with chronic intestinal failure (CIF) due to short bowel syndrome (SBS) with jejunocolonic anastomosis (SBS-2). Few or no data are available on SBS with jejunostomy (SBS-1) and CIF due to intestinal dysmotility (DYS) or mucosal disease (MD). We profiled the fecal microbiota of various pathophysiological mechanisms of CIF. METHODS: Cross-sectional study on 61 adults with CIF (SBS-1 30, SBS-2 17, DYS 8, MD 6). Fecal samples were collected and profiled by 16S rRNA amplicon sequencing. Healthy controls (HC) were selected from pre-existing cohorts, matched with patients by sex and age. RESULTS: Compared to HC, SBS-1, SBS-2 and MD patients showed lower alpha diversity; no difference was found for DYS. In beta diversity analysis, SBS-1, SBS-2 and DYS groups segregated from HC and from each other. Taxonomically, the CIF groups differed from HC even at the phylum level. In particular, CIF patients' microbiota was dominated by Lactobacillaceae and Enterobacteriaceae, while depleted in typical health-associated taxa belonging to Lachnospiraceae and Ruminococcaceae. Notably, compositional peculiarities of the CIF groups emerged. Furthermore, in the SBS groups, the microbiota profile differed according to the amount of parenteral nutrition required and the duration of CIF. CONCLUSIONS: CIF patients showed marked intestinal dysbiosis with microbial signatures specific to the pathophysiological mechanism of CIF as well as to the severity and duration of SBS.

Non-interventional, 5-year retrospective data of home parenteral nutrition in patients with benign chronic intestinal failure: Analysis of an Italian nurse registry (SERECARE II).

OBJECTIVE: This study is an assessment of home parenteral nutrition service performance and safety and efficacy outcomes in patients with benign chronic intestinal failure. METHODS: This is a retrospective, non-interventional, and multicenter study. Data were collected by trained nurses and recorded in a dedicated registry (SERECARE). RESULTS: From January 1, 2013 to June 30, 2018, data from a total of 683 patients with benign chronic intestinal failure were entered in the registry. Patients included 208 pediatric (53.8% male; median age = 4.0 y) and 475 adult (47.6% male; median age = 59.0 y) participants. On average, patients were visited 5.4 ± 4.5 times and received 1.4 ± 0.8 training sessions. Retraining was not common and mostly due to change of therapy or change of caregiver. Of 939 complications, 40.9% were related to the central venous catheter and were mostly infectious (n = 182) and mechanical (n = 187). The rate of infectious and mechanical complications per 1000 catheter days decreased over 5 y (0.30-0.15 and 0.33 -0.19, respectively). The rate of complications per 1000 catheter days and the mean complications per patient were higher in pediatric than in adult patients. The hospitalization rate was 1.01 per patient throughout the study period. These data were similar to those registered in a previous study period (2002-2011) (n = 1.53 per patient). Changes over time in the efficacy variables were mostly small and non-significant. CONCLUSIONS: This study confirms the importance of setting up and maintaining structured registries to monitor and improve home parenteral nutrition care. Safety outcomes have improved over the years, most likely due to the underlying efficient nursing service.