Acute intestinal failure: international multicenter point-of-prevalence study

Background & aims: Intestinal failure (IF) is defined from a requirement or intravenous supplementation due to failing capacity to absorb nutrients and fluids. Acute IF is an acute, potentially reversible form of IF. We aimed to identify the prevalence, underlying causes and outcomes of acute IF. Methods: This point-of-prevalence study included all adult patients hospitalized in acute care hospitals and receiving parenteral nutrition (PN) on a study day. The reason for PN and the mechanism of IF (if present) were documented by local investigators and reviewed by an expert panel. Results: Twenty-three hospitals (19 university, 4 regional) with a total capacity of 16,356 acute care beds and 1237 intensive care unit (ICU) beds participated in this study. On the study day, 338 patients received PN (21 patients/1000 acute care beds) and 206 (13/1000) were categorized as acute IF. The categorization of reason for PN was revised in 64 cases (18.9% of total) in consensus between the expert panel and investigators. Hospital mortality of all study patients was 21.5%; the median hospital stay was 36 days. Patients with acute IF had a hospital mortality of 20.5% and median hospital stay of 38 days (P > 0.05 for both outcomes). Disordered gut motility (e.g. ileus) was the most common mechanism of acute IF, and 71.5% of patients with acute IF had undergone abdominal surgery. Duration of PN of ≥42 days was identified as being the best cut-off predicting hospital mortality within 90 days. PN ≥ 42 days, age, sepsis and ICU admission were independently associated with 90-day hospital mortality. Conclusions: Around 2% of adult patients in acute care hospitals received PN, 60% of them due to acute IF. High 90-day hospital mortality and long hospital stay were observed in patients receiving PN, whereas presence of acute IF did not additionally influence these outcomes. Duration of PN was associated with increased 90-day hospital mortality

Home parenteral nutrition provision modalities for chronic intestinal failure in adult patients:An international survey

Background & aims: The safety and effectiveness of a home parenteral nutrition (HPN) program depends both on the expertise and the management approach of the HPN center. We aimed to evaluate both the approaches of different international HPN-centers in their provision of HPN and the types of intravenous supplementation (IVS)-admixtures prescribed to patients with chronic intestinal failure (CIF). Methods: In March 2015, 65 centers from 22 countries enrolled 3239 patients (benign disease 90.1%, malignant disease 9.9%), recording the patient, CIF and HPN characteristics in a structured database. The HPN-provider was categorized as health care system local pharmacy (LP) or independent home care company (HCC). The IVS-admixture was categorized as fluids and electrolytes alone (FE) or parenteral nutrition, either commercially premixed (PA) or customized to the individual patient (CA), alone or plus extra FE (PAFE or CAFE). Doctors of HPN centers were responsible for the IVS prescriptions. Results: HCC (66%) was the most common HPN provider, with no difference noted between benign-CIF and malignant-CIF. LP was the main modality in 11 countries; HCC prevailed in 4 European countries: Israel, USA, South America and Oceania (p < 0.001). IVS-admixture comprised: FE 10%, PA 17%, PAFE 17%, CA 38%, CAFE 18%. PA and PAFE prevailed in malignant-CIF while CA and CAFE use was greater in benign-CIF (p < 0.001). PA + PAFE prevailed in those countries where LP was the main HPN-provider and CA + CAFE prevailed where the main HPN-provider was HCC (p < 0.001). Conclusions: This is the first study to demonstrate that HPN provision and the IVS-admixture differ greatly among countries, among HPN centers and between benign-CIF and cancer-CIF. As both HPN provider and IVS-admixture types may play a role in the safety and effectiveness of HPN therapy, criteria to homogenize HPN programs are needed so that patients can have equal access to optimal CIF care

Intestinal microbiome in chronic intestinal failure and associations with intestinal failure associated liver disease

Background and Aims: Intestinal dysbiosis has been described in children with chronic intestinal failure (CIF) and in adults with short bowel syndrome (SBS), mostly with jejunocolic anastomosis (SBS-2) and jejuno-ileal anastomosis (SBS-3), linked to generic data with the pathogenesis of Intestinal Failure Associated Liver Disease (IFALD). Little is known about gut microbiome of adults with end-jejunostomy (SBS-1) and in CIF other than SBS and any specific associations with the onset of IFALD. We aimed to describe the fecal microbiome of adult patients with different mechanisms of CIF and any possible associations with the development of IFALD. Material and methods: Fecal samples from 61 patients with benign CIF. Phylogenetic characterization of the microbiome by amplification of the hypervariable regions V3 and V4 of the bacterial gene encoding 16S rRNA, and subsequent grouping of sequences in amplicon sequence variants (ASVs). Patient samples comparison to microbiome sequences from 61 healthy subjects, matched for sex and age, selected from the healthy subjects library of the Laboratory of the Microbial Ecology of Health Unit, Department of Pharmacy and Biotechnology, of the University of Bologna. IFALD was assessed by the diagnostic criteria of IFALD-cholestasis, IFALD-steatosis, IFALD-fibrosis. Results: Decreased bacterial α-diversity in CIF patients (increase of Proteobacteria and Actinobacteria and decrease in Bacteroidetes). Identification of microbial family-level signatures specific for CIF mechanisms (increase in Actinomycetaceae and Streptococcaceae in SBS-1, Bifidobacteriaceae and Lactobacillaceae in SBS-2, Bacteroidaceae and Porphyromonadaceae in dysmotility). Abundance of Lactobacillus and Lactobacillaceae strongly associated with IFALD-cholestasis and IFALD–fibrosis for SBS-1; Peptostreptococcus, Prevotellaceae (Prevotella) and Pasteurellaceae (Haemophilus) significantly increased in IFALD-fibrosis for other CIF mechanisms. Conclusions: CIF patients had a marked intestinal dysbiosis with microbial family-level signatures specific to the pathophysiological mechanism. Specific characteristics of microbiome may contribute to the pathogenesis of IFALD. Intestinal microbiome could become a therapeutic target in patients with CIF

Expected benefits and motivation to weight loss in relation to treatment outcomes in group-based cognitive-behavior therapy of obesity

Purpose: We aimed to determine cognitive drivers, expected to play a role in target reach and/or attrition in obesity programs. Methods: We recorded the expected benefits of weight loss, weight targets, primary motivation for weight loss, perceived treatment needs, readiness and self-confidence to be successful and a battery of psychopathology questionnaires in 793 subjects with obesity (68% women; mean age 48.7; 46% obesity class III) enrolled into a group-based cognitive-behavioral treatment program. Their relevance on attrition and successful weight loss outcome were tested by logistic regression analysis. Results: The expected benefits of weight loss scored very high in all physical, psychological and social areas, with differences between genders. Attrition rate was 24, 41 and 65% at 6-, 12-, and 24-month follow-up. Average weight loss was 5.8 \ub1 7.1\ua0kg ( 12 4.8%) at 6\ua0months, with 17% of cases (32% of continuers) maintaining weight loss > 10% at 24\ua0months. After adjustment for confounders, attrition was reduced by concern for present health, motivation/consciousness of the importance of physical activity and need for support; treatment discontinuation was favored by concern for body image, by expectations for drug treatment or bariatric surgery, and by high-challenging weight loss targets. Male gender, higher BMI and concern for present health predicted weight loss > 10%, whereas concern for body appearance was associated with lower probability of attaining the desired weight loss targets. Conclusion: A more precise definition of needs and expectations might help tailor treatment to individual patients, but attrition rates and target reach remain difficult to predict. Level of evidence: Level V, descriptive studies

Assessment of Intestinal Failure Associated Liver Disease according to different diagnostic criteria

Background &amp; aims: Intestinal failure associated liver disease (IFALD) has been defined using numerous criteria; however the clinical relevance of these criteria has never been compared. We therefore aimed to evaluate the prevalence, incidence, evolution of IFALD diagnosed by different criteria and to assess any clinical features that may be associated with its occurrence. Methods: A cross sectional (CS) and retrospective study were carried out on adults on home parenteral nutrition (HPN) for chronic intestinal failure (CIF) managed at a single center. Inclusion criteria at CS: age 6518 years, benign disease. Collected data included: patient demographics, CIF and HPN characteristics, episodes of central venous catheter related bloodstream infection (CRBSI). IFALD was diagnosed by 9 criteria based on liver function tests and liver ultrasound (US) imaging. IFALD diagnoses were categorized as steatosis (2 criteria), cholestasis (3 criteria) or fibrosis (2 criteria) and unclassified (2 criteria). Prevalence was assessed at CS and at starting HPN (baseline, BS). Evolution was assessed as change of IFALD between BS and CS. Incidence was calculated as patients who developed IFALD from BS to CS. Results: A total of 113 patients were included. At CS, IFALD prevalence range in each diagnostic categories was: cholestasis 5\u201315%; steatosis 17\u201343%; fibrosis 10\u201320%; unclassified 7\u201338%. A 28.5% of patients did not have IFALD according to any criteria. Two cholestasis criteria and one fibrosis criterion were significantly (P &lt; 0.05) associated with a short bowel syndrome as the pathophysiological mechanism of CIF, HPN requirement and the number of CRBSI episodes. At BS, IFALD prevalence range was: cholestasis 13\u201340%; steatosis 27\u201390%; fibrosis 2\u20135%; unclassified 8\u201375%. The incidence range of IFALD was: cholestasis 0\u20137%; steatosis 0\u201339%; fibrosis 7\u201318%; unclassified 4\u20139%. IFALD steatosis diagnosed by US was the most frequent diagnosis at both CS prevalence and incidence assessments. Notably, IFALD criteria normalized in various percentages (2\u201370%), depending on the diagnostic categories, between BS and CS. Conclusions: This is the first study to systematically demonstrate that the frequency of IFALD varies greatly depending on diagnostic criteria used, confirming the need for a consensus definition to be used between different national and international IF units. IFALD can be present at HPN initiation but may resolve thereafter; further work is required to evaluate the factors associated with improvement

Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction

Background: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). Key Messages: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease. Conclusions: A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies

Outcome of kidney function in adults on long-term home parenteral nutrition for chronic intestinal failure

Objective: The aim of this study was to evaluate kidney function outcome in adults on home parenteral nutrition (HPN) for chronic intestinal failure using the newly recommended equations for estimated glomerular filtration rate (eGFR) assessment in clinical practice. Methods: This was an observational study with 72 patients. Clinical and biochemical parameters were collected at initiation of HPN (retrospective baseline [BL]), at inclusion in the study (cross-sectional [CS]), and at the end of a 30-mo prospective follow-up (Fup). The eGFR (mL/min/1.73 m2 body surface) was calculated by the Chronic Kidney Disease Epidemiology Collaboration creatinine and categorized as normal, mildly decreased (MDKF), and chronic kidney disease (CKD) when 6590, 60 to 89, and <60, respectively. Results: An eGFR<90 was observed in 41.7% of patients at BL, 53.4% at CS, and 56.6% at Fup. A CKD was present in all of the patients at BL, 20.1% at CS, and 35.9% at Fup. The probability of maintaining an eGFR 6560 was 98%, 82%, and 79% at 1, 5, and 10 y after BL, respectively (Kaplan-Meier analysis). The probability was lower in patients with MDKF at BL (P = 0.039). The development of a CKD was significantly associated with aging and urologic diseases and numerically associated with the episodes of venous-catheter sepsis, short bowel syndrome, and a low volume of HPN. Conclusions: In patients on HPN for chronic intestinal failure, decreased kidney function is a frequent finding, even at HPN commencement, demanding accurate monitoring during the treatment. Prevention of CKD primarily relies on the maintenance of fluid balance and the prevention of catheter-sepsis and urologic diseases

Nutrition in Patients with Type 2 Diabetes: Present Knowledge and Remaining Challenges

Unhealthy behaviours, including diet and physical activity, coupled with genetic predisposition, drive type 2 diabetes (T2D) occurrence and severity; the present review aims to summarise the most recent nutritional approaches in T2D, outlining unmet needs. Guidelines consistently suggest reducing energy intake to counteract the obesity epidemic, frequently resulting in sarcopenic obesity, a condition associated with poorer metabolic control and cardiovascular disease. Various dietary approaches have been proposed with largely similar results, with a preference for the Mediterranean diet and the best practice being the diet that patients feel confident of maintaining in the long term based on individual preferences. Patient adherence is indeed the pivotal factor for weight loss and long-term maintenance, requiring intensive lifestyle intervention. The consumption of nutritional supplements continues to increase even if international societies do not support their systematic use. Inositols and vitamin D supplementation, as well as micronutrients (zinc, chromium, magnesium) and pre/probiotics, result in modest improvement in insulin sensitivity, but their use is not systematically suggested. To reach the desired goals, patients should be actively involved in the collaborative development of a personalised meal plan associated with habitual physical activity, aiming at normal body weight and metabolic control

Functional lipidomics in patients on home parenteral nutrition: Effect of lipid emulsions

AIM To investigate the fatty acid-based functional lipidomics of patients on long-term home parenteral nutrition receiving different intravenous lipid emulsions. METHODS A cross-sectional comparative study was carried out on 3 groups of adults on home parenteral nutrition (HPN), receiving an HPN admixture containing an olive-soybean oil-based intravenous lipid emulsion (IVLE) (OO-IVLE; n = 15), a soybean- medium-chain triacylglycerol-olivefish oil-based IVLE (SMOF-IVLE; n = 8) or HPN without IVLE (No-IVLE; n = 8) and 42 healthy controls (HCs). The inclusion criteria were: duration of HPN â\u89¥ 3 mo, current HPN admixtures â\u89¥ 2 mo and HPN infusions â\u89¥ 2/wk. Blood samples were drawn 4-6 h after the discontinuation of the overnight HPN infusion. The functional lipidomics panel included: the red blood cell (RBC) fatty acid (FA) profile, molecular biomarkers [membrane fluidity: saturated/monounsaturated FA ratio = saturated fatty acid (SFA)/monounsaturated fatty acid (MUFA) index; inflammatory risk: n-6/n-3 polyunsaturated fatty acid (PUFA) ratio = n-6/n-3 index; cardiovascular risk: sum of n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) = n-3 index; free radical stress: sum of FA trans isomers = %trans index] and FA pathway enzyme activity estimate (delta-9-desaturase = D9D; delta-6-desaturase = D6D; delta-5-desaturase = D5D; elongase = ELO). Statistics were carried out using nonparametric tests. The amount of each FA was calculated as a percentage of the total FA content (relative%). RESULTS In the OO-IVLE group, the percentage of oleic acid in the RBCs was positively correlated with the weekly load of OO-IVLE (r = 0.540, p = 0.043). In the SMOFIVLE cohort, the RBC membrane EPA and DHA were positively correlated with the daily amount of SMOFIVLE (r = 0.751, p = 0.044) and the number of HPN infusions per week (r = 0.753; p = 0.046), respectively. The SMOF-IVLE group showed the highest EPA and DHA and the lowest arachidonic acid percentages (p < 0.001). The RBC membrane linoleic acid content was lower, and oleic and vaccenic acids were higher in all the HPN groups in comparison to the HCs. Vaccenic acid was positively correlated with the weekly HPN load of glucose in both the OO-IVLE (r = 0.716; p = 0.007) and the SMOF-IVLE (r = 0.732; p = 0.053) groups. The estimated activity of D9D was higher in all the HPN groups than in the HCs (p < 0.001). The estimated activity of D5D was lower in the SMOF-IVLE group than in the HCs (p = 0.013). The SFA/MUFA ratio was lower in all the HPN groups than in the HCs (p < 0.001). The n-6/n-3 index was lower and the n-3 index was higher in the SMOF-IVLE group in comparison to the HCs and to the other HPN groups (p < 0.001). The %trans index did not differ among the four groups. CONCLUSION The FA profile of IVLEs significantly influenced the cell membrane functional lipidomics. The amount of glucose in the HPN may play a relevant role, mediated by the insulin regulation of the FA pathway enzyme activities