Body composition predicts clinical outcome in patients with intestinal failure on long-term home parenteral nutrition.

BACKGROUND & AIMS: Patients with chronic intestinal failure (CIF) are at risk of altered body composition and impaired muscle function, which may negatively affect clinical outcome. The aim of this study was to investigate the predictive value of body composition and muscle strength in relation to clinical outcome in CIF patients on long-term home parenteral nutrition (HPN). METHODS: This was an observational cohort study comprising 77 clinically stable patients with CIF on HPN (>12 months). At inclusion, we recorded demographic data and information regarding anthropometry, body composition assessed by bioelectrical impedance and muscle strength by hand grip strength. Number of yearly hospital readmissions and length of hospital stay (LOS) as well as all-cause mortality characterized clinical outcome. Assessment parameters were categorized according to normative reference values. RESULTS: The average number of readmissions was 2.0 ± 1.8 per year and the average LOS was 23.2 ± 23.6 days. In univariate analysis phase angle (PA, p = 0.009) and handgrip strength (HGS, p = 0.012) were associated with the number of readmissions. Multivariate analysis confirmed the independence and significance of the association for PA (coefficient -0.5 [95% CI; -0.9 to -0.2]; p = 0.007). In addition, PA was associated with LOS in univariate analysis (p = 0.019), while none of the remaining parameters were significantly associated with LOS. During the follow-up period (median 24.3 months), 16 (20.8%) patients died and the cumulative mortality rate was 14.3% after two years. Fat free mass index (FFMI) below normal (Hazard Ratio 3.9 [95% CI; 1.1-14.1]; p = 0.04) and PA below normal (Hazard Ratio 5.3 [95% CI; 1.6-17.5]; P = 0.007) were identified as independent risk factors for mortality. CONCLUSIONS: Phase angle significantly predicted number of readmissions, length of hospital stay and mortality in patients with intestinal failure on long-term parenteral nutrition, while fat free mass index only predicted mortality.

The impact of home parenteral nutrition on the burden of disease including morbidity, mortality and rate of hospitalisations.

INTRODUCTION: Home parenteral nutrition (HPN) provides fluid and nutrition essential for the survival of patients with type 3 intestinal failure (IF). However, it is associated with complications and re-admission to hospital. This study aims to investigate the effect of HPN on mortality, morbidity and hospital re-admissions. METHOD: This is a retrospective cohort study. All patients newly dependent on HPN discharged over a 4-year period between 2011 and 2015 were included. Patients' characteristics, nutritional status and diagnosis were recorded, along with frequency and duration of HPN administration. Outcomes collected included hospital re-admissions, morbidity, catheter related blood stream infections (CRBSIs) and mortality. Regression analyses were performed to estimate the rate of different outcomes adjusted for prognostic factors. RESULTS: There were 210 patients included, 561 separate HPN prescriptions equating to 110,537 catheter days. Total number of deaths was 44 (0.398 deaths per 1000 catheter days). There were 196 re-admissions to hospital recorded for a total of 5594 days, 69 (33%) of these re-admissions were unplanned (2484 days in hospital). Principle reasons for unplanned re-admissions included: CRBSIs (n = 31, 45%); other sepsis (n = 10, 14.5%) and abdominal symptoms (n = 9, 13%). CRBSIs were recorded in 22 (10%) patients, equating to a rate of 0.199 per 1000 catheter days. Days per week on HPN increased the relative rate (RR) of time in hospital due to any reason or for unplanned readmissions, RR 1.50 (95% CI: 1.26, 1,78 p < 0.001) and RR 1.39 (95% CI: 1.10, 1.75 p = 0.006) respectively. However, there was no association between days per week on HPN and CRBSI occurrence. CONCLUSION: Unplanned re-admissions for patients with IF accounted for a third of all hospitalisations in those on HPN and the majority were due to CRBSI. The number of HPN dependent days per week was related to all-cause unplanned re-admissions, although not to CRBSI rate.

New mutations of EpCAM gene for tufting enteropathy in Saudi Arabia.

BACKGROUND/AIM: Tufting enteropathy (TE) is a rare cause of congenital intractable diarrhea in children. It often results in an irreversible intestinal failure and total parenteral nutrition (TPN) dependency; eventually, intestinal transplantation may be necessary. Data on TE from the Middle East are scarce; therefore, our aim of conducting this study was to clarify the clinical, histopathologic, and molecular features of TE in Saudi children. PATIENTS AND METHODS: This was a retrospective chart review of four children with TE who presented between January 2011 and December 2013 to King Fahad Specialist Hospital-Dammam (KFSH-D). The diagnosis of TE was suspected based on characteristic histopathologic intestinal biopsy findings and confirmed by EpCAM gene testing. RESULTS: Molecular testing identified two novel mutations in the EpCAM gene in our patients. These mutations were associated with severe phenotype of the disease characterized by very early onset (median of 2 weeks of life), TPN dependency, and death during early childhood. Two patients died due to central line-related complications. Two patients were referred for intestinal transplantation due to loss of intravenous access in one and progressive liver disease in the other. CONCLUSION: Mutations in EpCAM gene in Saudi children are characterized by severe phenotype and poor outcome.

Intestinal transplantation: indications and prospects.

Intestinal transplantation (IT) can involve small bowel transplantation alone, or be associated with liver or multivisceral transplantation. Although IT is the radical treatment for intestinal failure, home parenteral nutrition (PN) remains the treatment of choice for this disease. Indications for IT are still debated. A recent study showed that early referral for IT is recommended for patients with life-threatening combined liver and intestinal failure or for patients with invasive intra-abdominal desmoid tumors. In the same study, no survival benefit was shown for patients undergoing IT for ultra-short bowel or major complications related to the PN catheter; indications still need to be fully assessed. While short-term outcomes for IT have improved dramatically (one-year survival for small bowel-alone IT is now 80% versus 0-28% in the 1980s), long-term outcomes have not improved much since the introduction of Tacrolimus in the 1990s: five-year survival still does not exceed 60%. Some prospective developments could improve these results: the use of multivisceral grafts, the use of Sirolimus and Thymoglobulins in the immunosuppressive treatment, or the use of new biochemical markers for early diagnosis of graft rejection.

Long-term follow-up of patients on home parenteral nutrition in Europe: implications for intestinal transplantation.

BACKGROUND: The indications for intestinal transplantation (ITx) are still debated. Knowing survival rates and causes of death on home parenteral nutrition (HPN) will improve decisions. METHODS: A prospective 5-year study compared 389 non-candidates (no indication, no contraindication) and 156 candidates (indication, no contraindication) for ITx. Indications were: HPN failure (liver failure; multiple episodes of catheter-related venous thrombosis or sepsis; severe dehydration), high-risk underlying disease (intra-abdominal desmoids; congenital mucosal disorders; ultra-short bowel), high morbidity intestinal failure. Causes of death were defined as: HPN-related, underlying disease, or other cause. RESULTS: The survival rate was 87% in non-candidates, 73% in candidates with HPN failure, 84% in those with high-risk underlying disease, 100% in those with high morbidity intestinal failure and 54%, in ITx recipients (one non-candidate and 21 candidates) (p<0.001). The primary cause of death on HPN was underlying disease-related in patients with HPN duration ≤2 years, and HPN-related in those on HPN duration >2 years (p=0.006). In candidates, the death HRs were increased in those with desmoids (7.1; 95% CI 2.5 to 20.5; p=0.003) or liver failure (3.4; 95% CI 1.6 to 7.3; p=0.002) compared to non-candidates. In deceased candidates, the indications for ITx were the causes of death in 92% of those with desmoids or liver failure, and in 38% of those with other indications (p=0.041). In candidates with catheter-related complications or ultra-short bowel, the survival rate was 83% in those who remained on HPN and 78% after ITx (p=0.767). CONCLUSIONS: HPN is confirmed as the primary treatment for intestinal failure. Desmoids and HPN-related liver failure constitute indications for life-saving ITx. Catheter-related complications and ultra-short bowel might be indications for pre-emptive/rehabilitative ITx. In the early years after commencing HPN a life-saving ITx could be required for some patients at higher risk of death from their underlying disease.

Management of intestinal failure in the pediatric critical care setting.

Intestinal failure (IF) is a complex, chronic illness, of increasing importance in the pediatric critical care setting. We can expect an increase in pediatric IF given an increase in the survivors of extreme prematurity and complex congenital heart disease. Overall priorities for management of this condition include surgical and medical strategies to promote intestinal adaptation and to reduce complications, particularly related to malnutrition, liver disease and sepsis. In this review the authors propose that the optimal care for children with IF are multidisciplinary teams abreast of the newest strategies for intestinal rehabilitation. Early listing for intestinal transplantation for children at greatest risk of long-term parenteral nutrition dependency and its life threatening complications is appropriate.

Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea.

Autosomal-recessive congenital sodium diarrhea (CSD) is characterized by perinatal onset of a persistent watery diarrhea with nonproportionally high fecal sodium excretion. Defective jejunal brush-border Na(+)/H(+) exchange has been reported in three sporadic patients, but the molecular basis of the disease has not been elucidated. We reviewed data from a large cohort of CSD patients (n = 24) and distinguished CSD associated with choanal or anal atresia, hypertelorism, and corneal erosions--i.e., a syndromic form of CSD--occurring in ten families from an isolated form--i.e., classic CSD--presenting in seven families. Patients from both groups have a high risk of mortality due to immediate electrolyte imbalances and complications from long-term parenteral nutrition in the first years of life, but survivors can eventually adapt to partial or complete enteral nutrition. A genome-wide SNP scan was applied and identified a homozygous c.593-1G-->A splicing mutation in SPINT2, encoding a Kunitz-type serine-protease inhibitor, in one extended kindred with syndromic CSD. The same mutation and four distinct, homozygous or compound heterozygous mutations (p.Y163C, c.1A-->T, c.337+2T-->C, c.553+2T-->A) were identified in all syndromic patients. No SPINT2 mutations were found in classic-CSD patients. SPINT2 mutations were associated with loss of protein synthesis or failure to inhibit the serine protease trypsin in vitro. We delineate syndromic CSD as a distinct disease entity caused by SPINT2 loss-of-function mutations. SPINT2 mutations might lead to an excess of yet unknown serine protease activity in affected tissues.

[Multidisciplinary approach in the management of intestinal failure]. / Tratamiento multidisciplinario del fallo intestinal.

OBJECTIVE: [corrected] Our aim was to analyze our results in the management of intestinal failure with a multidisciplinary approach including optimized parenteral nutrition, reconstructive surgery and intestinal transplantation (ITx). MATERIAL AND METHODS: We included all patients evaluated by our team with the diagnosis of IF. We assessed outcome, mortality and complications in children that achieved adaptation and those listed for ITx. RESULTS: Seventy one children (40 boys, 31 girls) were evaluated between 1997 and 2006 because of IF. Forty eight (76%) were referred from other institutions. In 56 cases (80%) IF began in the newborn period. Causes of IF were: short bowel syndrome (52) intestinal motility disorders (16) and intestinal epithelial disorders (3). Median birth weight in the group of SBS was 2.2 Kg and prematurity was an associated condition in 15% of them. Overall, fourteen patients (20%) achieved intestinal adaptation with progressive weaning from PN, the management of these children consisted of optimized parenteral and enteral nutrition and autologous intestinal reconstructive surgery. Nine (13%) are stable under home parenteral nutrition regimen. Eight children (11%), all of them listed for liver and small bowel transplantation, died in the waiting list after a mean waiting time of more than 300 days, with a median of 4 laparotomies and 4 episodes of catheter related sepsis. Four children (5.6%) died in the adaptation process or before their inclusion on the waiting list. Finally, twenty five (35,2%) children underwent 28 intestinal transplantation: 9 isolated small bowel transplantation (SBTx), 16 combined liver and small bowel (CLSB) and 3 multivisceral (MVTx). Among transplanted patients, 9 (36%) died, (3 MVTx, 1 SBTx and 8 CLSB) and four were retransplanted. CONCLUSIONS: Intestinal Transplantation is an established alternative to parenteral nutrition in the treatment of IF, although complications and mortality rates are still considerable, especially MVTx and CLSBTx. Mortality in children listed for intestinal transplantation remains also high. Intestinal adaptation can be achieved with adequate rehabilitation therapy even in some cases with apparently irreversible intestinal transplantation. Early referral before liver failure or other complications arise is crucial is crucial in order to improve the outcome of these patients.

Intestinal replacement therapy: timing and indications for referral of patients to an intestinal rehabilitation and transplant program.

Current treatment options for patients suffering from intestinal insufficiency include all forms of intestinal replacement therapy (IRT). Parenteral nutrition has achieved extended success for the majority of patients requiring interval treatment, however, complications leading to failure of this treatment increases with the duration of therapy. There is currently no consensus as to the appropriate timing for transplantation of the intestine or the timing of referral for evaluation at a center experienced with this therapy. Certain patient characteristics warrant evaluation. Those patients with no jejunoileum who have guaranteed lifelong parenteral dependence, both adult and pediatric, should be immediately referred to a transplant center due to the high likelihood of the development of liver disease. Patients with metastatic infectious complications from catheter sepsis, patients with cholestasis seen intermittently with sepsis episodes, patients who are not successfully weaning and who demonstrate progressive thrombocytopenia, and patients with motility disorder experiencing deterioration should also warrant early referral to an intestinal rehabilitation and transplant program. The objective of evaluation is to maximize the opportunities for rehabilitation while not missing the critical window of opportunity for successful transplantation when needed. We favor an aggressive directed approach to rehabilitation, coupled with psychological preparation for both transplantations and other options. Early referral requires trust between the patient, referring physician, and the transplant team to assure that a rush to judgment will not lead to a premature transplant. The current wait list mortality is high, mandating early referral and listing with an approach aimed at maximizing both the success of gastrointestinal support, as well as of transplantation when necessary.

Cost and quality of life after intestinal transplantation.

Intestinal transplantation has become a standard treatment for intestinal failure in patients with life-threatening complications of TPN. Although the long-term survival of patients with continued parenteral nutrition is higher than after intestinal transplantation, the 1 and 2 year survival is comparable. Here we examine other aspects of the treatment options available for patients with intestinal failure including the cost of the therapy and the quality of life. The cost of parenteral nutrition compared to intestinal transplantation reveals that transplantation is cost-effective in patients that maintain graft function within 1 to 3 years after surgery. The quality of life after transplantation is probably equal to or better than quality of life on TPN and children report quality of life similar to normal school children. Although currently reserved for those with life-threatening complications, intestinal transplantation may soon be an option for any patient permanently dependent on parenteral nutrition.

Home parenteral nutrition: survival, cost, and quality of life.

This article summarizes what is known about which factors influence survival of patients on home parenteral nutrition, the costs related to this therapy, and the quality of life for patients living on home parenteral nutrition. The article refers to both North American and European experiences with this complex therapy.

Small bowel disease in the elderly: diarrhoea and malabsorption.

Diarrhoea and malabsorption are common problems in elderly persons. Worldwide, diarrhoea is the second leading cause of mortality. In the developed world, 85% of its mortality affects the elderly. The diagnostic work up for diarrhoea and malabsorption is more complex for the elderly than for the young patient. If diarrhoea persists for more than 24 h, oral rehydration solutions or intravenous fluids must be administered promptly in order to prevent hypotension and organ failure in the often multi-morbid patient. Both the immunocompromised patient and the severely affected out-patient should have stool culture performed. Malabsorption usually presents with weight loss, osteoporosis, anaemia, skin and neurological symptoms. The careful diagnostic work-up must aim at the identification of treatable disorders such as coeliac disease, Crohn's disease and bacterial overgrowth. Often, a detailed drug history is of help in identifying a readily treatable cause.

Growth and digestive function of turkeys surviving the poult enteritis and mortality syndrome.

Stunted growth of poults afflicted by enteritis mortality syndrome (PEMS) may be associated with depressed digestive capabilities. We conducted two experiments to test this hypothesis. Survivors of PEMS were obtained from a research flock that had been purposefully infected at 5 d of age with PEMS inoculum that included turkey corona virus. The PEMS survivors were assigned to Experiments 1 and 2, beginning at 40 and 35 d of age, respectively. Three groups (large, L; medium, M; and small, S) and two groups (L and S) of 20 poults each were selected to represent different degrees of stunting in Experiments 1 and 2, respectively. When the body weights of each group in both experiments were plotted using initial body weight as the starting point, all of the weights fell on the normal growth curve except Group S in Experiment 1. Therefore, there was no evidence of compensatory growth over the period studied. In Experiment 1, apparent fat absorption (AFA) was significantly higher (P < 0.05) for control (85.9%) than for M (78.5%) and S (78.3%) groups, and AME, for the control group was significantly higher than all the PEMS-survivor groups. In Experiment 2, Group L had a higher AFA and AMEn than Group S. AFA and AMEn improved in both groups over time. The digestive capabilities of PEMS survivors were depressed proportionally to the degree of stunting. Impaired fat digestibility and dietary energy utilization in PEMS-afflicted birds are likely contributors to stunted growth and reduced recovery rates.

Diarrhea and malabsorption in the elderly.

Physicians who care for elderly patients should be alert to the possible presence of diarrhea and malabsorption. Older patients may not admit to having chronic diarrhea, particularly if they also are incontinent. If diarrhea is of short duration, an infectious cause is at least as common as in the young. Institutionalized elderly are particularly prone to gastrointestinal infections, but the manifestations may not be overt. When an intestinal infection and potential medication-induced gastrointestinal disturbances have been excluded, the differential diagnosis of diarrhea in the elderly is the same as in the young. Causes include intestinal malabsorption, even though diarrhea is a less common manifestation of malabsorption in the old than in younger patients. In the elderly, micronutrient deficiency is a common presenting clinical picture; because the symptoms of malabsorption are covert, the diagnosis often is delayed, and nutritional deficiencies are more common and more severe than in the young. Because the elderly have less nutritional reserve than the young, these deficiencies are clinically much more devastating in the elderly. Although the causes of malabsorption, as a whole, are similar in older and younger patients, chronic pancreatic insufficiency of unknown cause and intestinal bacterial overgrowth without an anatomic abnormality of the small intestine are syndromes that are specific to the elderly and must be considered in any older patient with unexplained weight loss or failure to thrive. Often, therapeutic trials are necessary to establish a potential diagnosis.

D-xylose absorption as a measurement of malabsorption in poult enteritis and mortality syndrome.

Severe wasting of body tissues, diarrhea, high morbidity and mortality, and stunting are all characteristics of poult enteritis and mortality syndrome (PEMS). The wasting of musculature and loss of nearly all adipose tissue suggested that even though the PEMS-infected poults were eating some feed, nutrient intake was not sufficient to meet body requirements for maintenance and growth. Because epithelial cells in the gastrointestinal tract appeared to be a target of the undefined etiological agent (or agents) that causes PEMS, a study was conducted in which PEMS-infected poults were evaluated for malabsorption through 3 wk of age. D-Xylose, a poorly metabolized pentose, was given per os as a bolus, and blood samples were obtained from the ulnar vein in the wing of control and PEMS-infected poults over a 3-h period to estimate intestinal absorption. D-Xylose absorption in control poults peaked 30 to 60 min after the oral treatment, similar to results reported earlier. The PEMS-infected poults did not show a peak in absorption. The PEMS-infected poults showed significant delays in D-xylose absorption at 4, 7, and 11 d after PEMS challenge. The severe malabsorption and metabolic deficiency problem associated with PEMS was postulated to be a direct effect of the undefined infectious agent or agents that cause the disease.

[Parenteral nutrition at home]. / Zywienie pozajelitowe w domu.

Development of home parenteral nutrition (HPN) allowed for long term survival for patients with chronic intestinal failure, followed mainly total or near total small bowel resection. Own 11 years long experience with 49 HPN patients treated for 98 patients years with a HPN model adapted to polish conditions is presented. Long term survival (4 patients over 10 years) and low complications rate, comparable to reported from West European countries and USA, shows HPN possible in Poland and developed HPN model is efficient and safe method of life-restoring therapy with long term survival of patients with severe disturbances of absorption otherwise leading to death by starvation.

Short bowel syndrome in infancy and childhood. Analysis of survival in 60 patients.

This report concerns 60 infants and children with short bowel syndrome, most commonly caused by necrotizing enterocolitis in this study. Resection of atretic or gangrenous bowel was performed in 53 patients, tapering enteroplasty and primary anastomosis was performed in 13 patients, and temporary enterostomies were performed in 40 patients. Second-look laparotomy was useful in two of four cases of questionable bowel viability. The ileocecal valve was resected in 33 patients and remained intact in 27. The mean length of remaining bowel was 58.4 cm (range 13 to 150 cm). Seven patients with total aganglionosis and mid to proximal small bowel extension were managed with an initial enterostomy, whereas three had a pull-through procedure with an aganglionic patch enteroplasty. All patients received total parenteral nutrition and early enteral feedings. Home hyperalimentation was attempted when 50 percent of the calorie intake was enteral. Intestinal adaptation required from 3 to 14 months. Frequent setbacks were related to catheter sepsis, rotavirus infection, carbohydrate intolerance, and liver dysfunction. The overall survival rate was 85 percent, with mortality due to liver failure and sepsis associated with total parenteral nutrition.

Morbidity and mortality of short-bowel syndrome acquired in infancy: an update.

The advent of total parenteral nutrition (TPN) has made survival beyond infancy possible for large numbers of patients who have sustained massive small intestinal loss due to a variety of intraabdominal catastrophes. However, the quantity and quality of life have been limited by the development of late sequelae due both to the protracted use of TPN and the long-term complications of foreshortening of the gut. To determine to what extent the morbidity and mortality of short-bowel syndrome (SBS) may have improved over the last 10 years, we reviewed our experience since 1973 with patients losing more than 50% of total small intestinal mass in infancy. The etiologies of SBS in the 16 study patients were necrotizing enterocolitis (6), midgut volvulus (5), multiple atresias (3), gastroschisis (1), and congenital SBS (1). Overall survival was 81%; total small intestinal length (SIL) at the time of diagnosis was 44.2 +/- 7.9 cm in survivors and 30.3 +/- 7.8 cm in nonsurvivors, probability values not significant. Although no patient survived without an ileocecal valve whose total SIL was greater than 20 cm, the three deaths in this series were not related directly to the SIL, but to end-stage liver disease resulting from TPN-associated cholestasis. Among the survivors, adaptation to enteral feedings required 13.8 +/- 2.5 mo, during which time weaning from TPN occurred; weight at adaptation was 6.87 +/- 1.32 kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Amelioration of pale bird syndrome in chicks by vitamin E and selenium.

Vitamin E and/or selenium supplementation of a corn-soybean diet fed to broiler chicks in floor pens ameliorated the effect of an outbreak of pale bird syndrome diagnosed when the chicks were 3 weeks old. Supplementation significantly reduced both mortality and the effects of disease on body weight gain. The added nutrients only partly overcame the effect of the disease on body weight gain when infected chicks were compared with uninfected chicks.

[The problem of malabsorption after resection of the small intestine]. / "Zur Frage der Resorptionsstörungen nach Dünndarmresektionen".

During the period from 1971 to 1981 in 145 patients (108 adults and 37 children) partial resections of the intestine were practiced (in the surgical clinic of the Friedrich-Schiller-University, Jena). Fatality on the whole was about 25%. The surgical intervention with an extensive resection (more than 150 cm) was well tolerated by seven among 13 patients. Even in cases of shorter resections disturbances of resorption could be found especially for carbohydrates and vitamin B 12. Control examinations are necessary and therapeutic consequences have to be drawn.