Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study.

BACKGROUND & AIMS: Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here. METHODS: QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05 mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale. RESULTS: PS reductions were associated with QoL improvements (ANCOVA, p = 0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100 cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL. CONCLUSIONS: Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo.

Development and validation of the disease-specific Short Bowel Syndrome-Quality of Life (SBS-QoL™) scale.

BACKGROUND & AIMS: Subjects with short bowel syndrome (SBS) have impaired quality of life (QoL). No disease-specific instrument has been available to measure treatment-induced changes in QoL over time. Therefore, the aim was to develop and validate an SBS-specific QoL scale. METHODS: Classical test theory and Food and Drug Administration (FDA) guidance were applied for development and validation of the SBS-QoL™. Procedures included item generation and raw scale construction. Factor analysis, construct validity and internal consistency were assessed in a non-interventional observation, test re-test reliability and responsiveness in a randomised clinical study. RESULTS: The SBS-QoL™ comprises 17 items including two subscales. Subjects assessed the scale as easy to handle and comprehensible. Good construct validity was shown by comparison with the Home Parenteral Nutrition-Quality Of Life questionnaire as an external scale, which yielded moderately high correlation (r ≥ 0.7). High internal consistency was demonstrated (Cronbach's alpha: 0.94). Also the test re-test reliability was high (r ≥ 0.95), indicating reliable reproducibility of results. The Responsiveness Index (1.84) indicated the ability of the scale to detect changes in QoL over time. CONCLUSIONS: The SBS-QoL™ is an easy to handle and comprehensible SBS-specific subject-reported QoL scale. It is valid, reliable and sensitive with excellent psychometric characteristics to measure treatment-induced changes in QoL over time in subjects with SBS.

Differences in proteolytic activity and gene profiles of fungal strains isolated from the total parenteral nutrition patients.

Fungal infections constitute a serious clinical problem in the group of patients receiving total parenteral nutrition. The majority of species isolated from infections of the total parenteral nutrition patients belong to Candida genus. The most important factors of Candida spp. virulence are the phenomenon of "phenotypic switching," adhesins, dimorphism of fungal cells and the secretion of hydrolytic enzymes such as proteinases and lipases, including aspartyl proteinases. We determined the proteolytic activity of yeast-like fungal strains cultured from the clinical materials of patients receiving total parenteral nutrition and detected genes encoding aspartyl proteinases in predominant species Candida glabrata--YPS2, YPS4, and YPS6, and Candida albicans--SAP1-3, SAP4, SAP5, and SAP6. C. albicans released proteinases on the various activity levels. All C. glabrata strains obtained from the clinical materials of examined and control groups exhibited secretion of the proteinases. All 13 isolates of C. albicans possessed genes SAP1-3. Gene SAP4 was detected in genome of 11 C. albicans strains, SAP5 in 6, and SAP6 in 11. Twenty-six among 31 of C. glabrata isolates contained YPS2 gene, 21 the YPS4 gene, and 28 the YPS6 gene. We observed that clinical isolates of C. albicans and C. glabrata differed in SAPs and YPSs gene profiles, respectively, and displayed differentiated proteolytic activity. We suppose that different sets of aspartyl proteinases genes as well as various proteinase-activity levels would have the influence on strains virulence.

Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome.

BACKGROUND AND AIMS: Teduglutide, a GLP-2 analogue, may restore intestinal structural and functional integrity by promoting repair and growth of the mucosa and reducing gastric emptying and secretion, thereby increasing fluid and nutrient absorption in patients with short bowel syndrome (SBS). This 24-week placebo-controlled study evaluated the ability of teduglutide to reduce parenteral support in patients with SBS with intestinal failure. METHODS: In 83 patients randomised to receive subcutaneous teduglutide 0.10 mg/kg/day (n = 32), 0.05 mg/kg/day (n = 35) or placebo (n = 16) once daily, parenteral fluids were reduced at 4-week intervals if intestinal fluid absorption (48 h urine volumes) increased ≥ 10%. Responders were subjects who demonstrated reductions of ≥ 20% in parenteral volumes from baseline at weeks 20 and 24. The primary efficacy end point, a graded response score (GRS), took into account higher levels and earlier onset of response, leading to longer duration of response. The intensity of the response was defined as a reduction from baseline in parenteral volume (from 20% to 100%), and the duration of the response was considered the response at weeks 16, 20 and 24. The results were tested according to a step-down procedure starting with the 0.10 mg/kg/day dose. RESULTS: Using the GRS criteria, teduglutide in a dose of 0.10 mg/kg/day did not have a statistically significant effect compared with placebo (8/32 vs 1/16, p=0.16), while teduglutide in a dose of 0.05 mg/kg/day had a significant effect (16/35, p = 0.007). Since parenteral volume reductions were equal (353 ± 475 and 354 ± 334 ml/day), the trend towards higher baseline parenteral volume (1816 ± 1008 vs 1374 ± 639 ml/day, p=0.11) in the 0.10 mg/kg/day group compared with the 0.05 mg/kg/day group may have accounted for this discrepancy. Three teduglutide-treated patients were completely weaned off parenteral support. Serious adverse events were distributed similarly between active treatment groups and placebo. Villus height, plasma citrulline concentration and lean body mass were significantly increased with teduglutide compared with placebo. CONCLUSIONS: Teduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure. ClinicalTrials.gov number NCT00172185.

ESPEN Guidelines on Enteral Nutrition: Pancreas.

The two major forms of inflammatory pancreatic diseases, acute and chronic pancreatitis, require different approaches in nutritional management, which are presented in the present guideline. This clinical practice guideline gives evidence-based recommendations for the use of ONS and TF in these patients. It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. In mild acute pancreatitis enteral nutrition (EN) has no positive impact on the course of disease and is only recommended in patients who cannot consume normal food after 5-7 days. In severe necrotising pancreatitis EN is indicated and should be supplemented by parenteral nutrition if needed. In the majority of patients continuous TF with peptide-based formulae is possible. The jejunal route is recommended if gastric feeding is not tolerated. In chronic pancreatitis more than 80% of patients can be treated adequately with normal food supplemented by pancreatic enzymes. 10-15% of all patients require nutritional supplements, and in approximately 5% tube feeding is indicated.

Home enteral nutrition in adults: a European multicentre survey.

AIMS: This study was undertaken to report indications and practice of home enteral nutrition (HEN) in Europe. METHODS: A questionnaire on HEN practice was sent to 23 centres from Belgium (B), Denmark (D), France (F), Germany (G), Italy (I), Poland (P), Spain (S) and the United Kingdom (UK). This involved adult patients newly registered in HEN programme from 1 January 1998 to 31 December 1998. RESULTS: A total of 1397 patients (532 women, 865 men) were registered. The median incidence of HEN was 163 patients/million inhabitants/year (range: 62-457). Age distribution was 7.5%, 16-40 years; 37.1%, 41-65 years; 34.5%, 66-80 years and 20.9% >80 years. The chief underlying diseases were a neurological disorder (49.1%), or head and neck cancer (26.5%); the main reason for HEN was dysphagia (84.6%). A percutaneous endoscopic gastrostomy (58.2%) or a naso-gastric tube (29.3%) were used to infuse commercial standard or high energy diets (65.3%), or fibre diets (24.5%); infusion was cyclical (61.5%) or bolus (34.1%). Indications and feeds were quite similar throughout the different centres but some differences exist concerning the underlying disease. There was greater variation in the choice of tubes and mode of infusion. In F, G, I, S, and UK, costs of HEN are fully funded. In B, D, and P patients have to pay part or all of the charges. CONCLUSIONS: In Europe, HEN was utilised mainly in dysphagic patients with neurological disorders or cancer, using a standard feed via a PEG. However, there were important differences among the countries in the underlying diseases treated, the routes used, the mode of administration and the funding.

Central venous catheter complications in 447 patients on home parenteral nutrition: an analysis of over 100.000 catheter days.

RATIONALE: The purpose of this study is to report the frequency of central venous catheter (CVC) complications and to analyze the potential risk factors for complications requiring CVC removal in home parenteral nutrition (HPN) patients. METHODS: A questionnaire developed by the ESPEN HAN WORKING GROUP was distributed to 12 European centers to investigate the complications occurring during the period between January 1995 and December 2000 when HPN patients used their first CVC. The questionnaire collected informations related to the Home Parenteral Nutrition technique and the underlying disease. Factors affecting the time of CVC removal were jointly investigated using Cox's multivariable regression models. RESULTS: The study was performed on 447 patients for a total of 110869 CVC-days. Complications occurred in about 1/4 of patients, approximately half were infections and about half required Central Venous Catheter removal. The Cox analysis showed that using the CVC 7 times/week and implanted ports were associated with a hazard ratio of 3 and 2.8, respectively. A reduced risk of removal (of about 40%) was associated with using CVC also for non-nutritional purposes (P = 0.0016). CONCLUSIONS: Within the limits of this retrospective investigation, the type of CVC, the type of administration of HPN and the type of training are important factors associated with occurrence of complications or with CVC removal. However, in our opinion, proper care of the CVC, of preparation and administration of the nutritive admixture seem to be paramount for a safe management of HPN.

[Dynamic of IL-6 and IL-8 concentrations in patients after surgery treated with total parenteral nutrition]. / Dynamika zmian stezenia interleukin 6 i 8 u chorych po zabiegach chirurgicznych leczonych calkowitym zywieniem pozajelitowym.

Exaggerated cytokines productions and development of systemic inflammatory response (SIRS) is the most common cause of postoperative complications and death after major abdominal surgery. The present study was conducted to investigate alterations in systemic production of interleukin-6 (IL-6) and interleukin-8 (IL-8) after total parenteral nutrition (TPN) in surgical patients. Plasma concentrations of IL-6 and IL-8 were measured in 22 patients (10 treated with TPN and 12 without TPN) before major surgery and on the days 1, 3, 7, 10 and 14-16 after, by ELISA test (indications for surgery: stomach, pancreatic and colon carcinoma, complications of IBD and acute pancreatitis). There were no differences between preoperative levels of IL-6 and IL-8 in the examined groups of patients. The highest (on the days 1, 3, 7, 10: 268.3 (p = 0.002), 41.9 (p = 0.03), 122.6 (p = 0.009), 29.3 (p = 0.03) pg/ml respectively) and longer lasting significantly elevated level of IL-6 was observed in the group of patients after major surgery without TPN. In the group of patients received TPN (with glutamine) there was a significantly increased but in comparison with group of patients without TPN, significantly lower level of IL-6 on days 1 and 7 (103.4 and 34.7 pg/ml respectively, p = 0.01). There was no significant change in postoperative concentration of IL-8 after major surgery in the group of patients treated with TPN. The level of IL-8 was significantly elevated (p = 0.01) in the group of patients without TPN on day 1 and 3 following surgery. The IL-8 level in the TPN group vs. group of patients without TPN was significantly lower on day 1 after surgery. After TPN concentration of cholesterol was significantly higher and CRP level significantly lower. We conclude that TPN improved immunological response to major surgical trauma by reduction of the inflammatory response.

Clinical, social and rehabilitation status of long-term home parenteral nutrition patients: results of a European multicentre survey.

BACKGROUND: Home parenteral nutrition (HPN) is a lifesaving treatment in patients with intestinal failure. Dependency of nutritional support becomes permanent for the majority of patients who had received HPN for at least 2 years. The alternative to long term HPN in selected patients is intestinal transplantation. AIMS: To study some of the clinical, social and rehabilitation aspects of long-term HPN treatment. METHODS: A survey was performed in nine European HPN centres. The questionnaire covered epidemiologic data, underlying diseases, intestinal anatomy, nutritional support and status, marital status, rehospitalization rate, HPN complications, rehabilitation score, drugs use, coexistent diseases and interest in intestinal transplantation. For some items, data were collected within 12 months prior to the evaluation. RESULTS: This survey included 228 patients with a median age of 49 years. The median duration of HPN was 7 years (range 2--24 years). Short bowel length less than 100 cm was reported in 65% of patients with a predominance of end-jejunostomy or jejuno-colonic anastomosis. Global subjective nutritional status was normal in 79% of the patients, who were supplied with a mean number of 5.6 bags of parenteral nutrition weekly. Rehospitalizations within the 12 months prior to evaluation accounted for a mean period of 23 days and were due to HPN complications in half of the cases. Catheter-related sepsis was the most frequent HPN-complication. Bone metabolism disorders, which seemed to be more common than liver diseases, were directly related to HPN duration. One-third of the HPN patients was regularly consuming analgesics or opiates. HPN impair complete rehabilitation status but may improve the status of patients who had a very low rehabilitation score before starting HPN. An interest of intestinal transplantation was noted in only 10% of medical teams and in 8% of HPN patients. CONCLUSIONS: This study is the largest European survey on long-term HPN patients with long standing or permanent intestinal failure. Data enlighten clinical, social and rehabilitation aspects of patients who could face the option of intestinal transplantation in the future.

[Cellular immunity changes after total parenteral nutrition enriched with glutamine in patients with sepsis and malnutrition]. / Wplyw zywienia pozajelitowego wzbogaconego glutamina na wybrane wskazniki odpornosci komórkowej u niedozywionych chorych chirurgicznych z masywnym zakazeniem.

The influence of glutamine on human immune system is multidirectional but the exact changes still remain unclear. In this study the effect of total parenteral nutrition (TPN) enriched with glutamine on some selected immunological and nutritional parameters was examined in twelve surgical patients with sepsis and malnutrition. The reason for glutamine supplementation was lack of clinical improvement after standard TPN. All patients received TPN enriched with glutamine for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4, CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine administration and two days after (day 12) glutamine withdrawal. Simultaneously some nutritional parameters were assessed. The number and percentage of CD4, CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the same level during observation (with exception in CD4 on day 6, 12 and CD56 on day 4). No significant differences in CD8 and HLA-DR number and percentages were observed after TPN enriched with glutamine. BIA examination revealed on days 2 and 12 significant decrease of total body water and significant increase of body cell mass, intracellular water on day 12. It was correlated with significant higher total lymphocytes count and significantly higher total protein, serum albumin, transferrin, cholesterol and CRP concentration. Results demonstrated that TPN supplemented with glutamine improved rapidly some immunological and nutritional parameters in surgical, malnutrition patients with sepsis.

Home parenteral nutrition in adults: a european multicentre survey in 1997. ESPEN-Home Artificial Nutrition Working Group.

A retrospective survey on home parenteral nutrition (HPN) in Europe was performed from January to December 1997. Data were compared to a similar study performed in 1993. A questionnaire of HPN practice was designed by the members of the ESPEN-HAN group. This involved adult patients (older than 16 years) newly registered in an HPN program between 1 January and 31 December 1997 and included: number of patients, underlying diseases and a 6-12 month outcome. Incidence and prevalence (at 1.1.1998) of adult HPN were calculated according to the estimated total population in 1997 for the countries in which more than 80% of HPN patients were reported.A total of 494 patients were registered in 73 centres from nine countries (Belgium (B), Denmark (D), France (F), Poland (P), Spain (S), Sweden (Sw), United Kingdom (UK), The Netherlands (N) and Germany (G). The underlying diseases for HPN in 494 patients were cancer (39%), Crohn's (19%), vascular diseases (15%), radiation enteritis (7%), AIDS (2%), other diseases with intestinal failure (18%). Incidence (patients/million inhabitants/year) were in N (3), F. (2.9), D. (2.8), B. (2.6), UK (1. 2), S (0.7) and P (0.36), respectively. Prevalence were in D. (12.7). U.K. (3.7), N. (3.7), F (3.6), B (3.0), P (1.1), S (0.65). After this 6-12 months follow-up (n=284), the mortality was respectively 4% in Crohn's disease, 13% in vascular diseases, 16% in others, 21% in radiaton enteritis, 34% in AIDS, 74% in cancer. Incidences and prevalences modestly increased in these seven European countries in 1997 in comparison to 1993. The percentages of underlying diseases in these countries remained similar except for AIDS that significantly decreased (from 7% to 2%). Outcomes did not significantly differ in the 4-year period except for AIDS (34% instead of 88% mortality) and could have been related to newer, more efficacious therapy.

[Clinical evaluation of amino acid solution]. / Ocena kliniczna roztworu aminokwasów.

Glutamine, a conditionally essential amino acid, is important for immune function. It is now being formulated for incorporation in to total parenteral nutrition (TPN). The aims of this study were to examine the effect of glutamine administration on clinical status, body composition, protein synthesis and immune function in critically ill patients with sepsis. Eleven patients were included into the study. Seven of them have been on conventional TPN for 8-63 days without significant clinical and nutritional improvement. Glutamine supplemented TPN was implemented for 10 subsequent days. Before, during and after the study venous blood samples were taken for the cellular immunity examination, and for the measurement of plasma albumin, transferrin and triglycerides levels. Nitrogen balance was calculated every day during the study. No side effects were noted. Patients receiving amino acid solution revealed improved nitrogen balance, body composition and body water distribution. Plasma proteins concentrations and immunological indices significantly increased during ten days TPN with Glamin. We confirm the beneficial effects of amino acid solution-supplemented TPN on nitrogen balance, plasma proteins, and immune status of critically ill patients.

[Computer program "PANCREAS"]. / Program komputerowy "PANCREAS".

Contemporary computer technology allows precise and fast large database analysis. Widespread and common use depends on appropriate, user friendly software, usually lacking in special medical applications. The aim of this work was to develop an integrated system designed to store, explore and analyze data of patients treated for pancreatic cancer. For that purpose the database administration system MS Visual Fox Pro 3.0 was used and special application, according to ISO 9000 series has been developed. The system works under MS Windows 95 with possibility of easy adaptation to MS Windows 3.11 or MS Windows NT by graphic user's interface. The system stores personal data, laboratory results, visual and histological analyses and information on treatment course and complications. However the system archives them and enables the preparation reports of according to individual and statistical needs. Help and security settings allow to work also for one not familiar with computer science.

[Pancreatic fistulas]. / Przetoki trzustkowe.

The aim of our study was retrospective analysis of causes and treatment results of pancreatic fistula. In years 1989-1996, 40 patients aged 14-74 years were treated for pancreatic fistula in the Department of Gastroenterologic Surgery of Medical University in Warsaw. The majority of patients (36 adults) were treated conservatively, with the use of parenteral nutrition, drainage and somatostatin (in case of 4 patients). The healing of pancreatic fistula occurred in 27 medically treated patients after 26 days of therapy (mean value), the remaining patients were treated surgically. The applied treatment was effective in 38 out of 40 cases, 2 patients died (5.0%) due to the complications not connected with pancreatic fistula. In our opinion, in early stages of treatment of pancreatic fistula the conservative therapy with the use of parenteral nutrition is the treatment of choice and elective surgery should be used in patients, in whom conservative treatment fails.

[Selected aspects of nutritional support in patients after liver transplantation]. / Wybrane aspekty leczenia zywieniowego u chorych po przeszczepieniu watroby.

The majority of liver transplanted patients are severely malnourished that increases the incidence of postoperative morbidity and mortality. The authors analysed the effects of nutritional support-total parenteral nutrition-in 11 adult orthotopic liver allograft recipients (9 women, 2 men) transplanted for chronic or acute liver failure in 1994-1997. 4.3-9.75 g of N/24h, 1200-1700 kcal in 1750-2750 ml, from 2-5th postoperative day was administered via central vein in all-in-one system for 4-46 days. Neither metabolic nor septic complications related to the nutrition were observed. The function of the transplanted liver was not impaired by the nutrition. One patient died in course of hepatic coma, 10 patients are alive and in good general condition (1-29 months). In conclusion, the total parenteral nutrition is safe, beneficial and thus recommended routine therapy in the treatment of the liver transplanted malnourished patients.

Home parenteral nutrition in adults: a multicentre survey in Europe in 1993.

A retrospective survey was performed in 1994, involving 496 adult home parenteral nutrition (HPN) cases, newly enrolled in the year 1993 from 13 European countries from 75 centres. From the 8 countries having registered more than 80% of cases (423 patients), incidence and prevalence ranged from 0.2 to 4.6 and 0.3 to 12.2 patients/10(6) population/year. In the patients studied, the diagnosis was cancer (42%), Crohn's disease (15%), vascular diseases (13%), radiation enteritis (8%), AIDS (4%) and other nonmalignant non-AIDS diseases (18%). Short bowel syndrome and intestinal obstruction were the two major indications for HPN in 31% and 22%, respectively. Seventy-three percent of the centres had a nutrition team. HPN was administered through a tunnelled venous central catheter in 73%, cyclical nocturnal infusions were used in 90% of patients, and intravenous feeding was the sole source of nutrition in 33%. Only 44% undertook HPN unaided. The present report indicates that cancer has now become the main indication for HPN in Europe; there was, however, a heterogeneous distribution of diseases amongst the reporting countries. The observed 9 (6-12)-month probability of survival was poor in AIDS (n = 8; 12%) and cancer patients (n = 78; 29%) but better for the other HPN indications (n = 115; 92%).

Aminophylline stability in total parenteral nutrition admixtures.

Aminophylline stability (dose 0.5 and 0.75 g) was estimated in typical AIO nutrient admixtures [Salviamin 12.5% 1000.0 cm3; Glucose 500 g; Intralipid 20% 500.0 cm3; Soluvit N; Vitalipid N Adult; Addamel N; total volume 3000.0 cm3] prepared in DIMIX bags [Diffuplast srl, Italy]. The pH. particle size distribution [Coulter Counter ZM] and theophylline concentration [Spectrophotometer Pye Unicam] were measured immediately after preparation and after 24, 48, 72 hours of storage in low temperature and then after 24 hours in room temperature. Aminophylline proved to be stable in above mentioned doses and now is commonly added into AIO in practice.

[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.