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

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

Association between Karnofsky performance status and outcomes in cancer patients on home parenteral nutrition.

BACKGROUND AND AIM: The selection of appropriate criteria is essential to accurately identify cancer patients eligible for home parenteral nutrition (HPN). In this study, the association between Karnofsky Performance Status (KPS) Scale scores and outcomes in cancer patients on HPN was evaluated. METHODS: Retrospective-observational-longitudinal-analytical study of a database of adult cancer patients on HPN. The variables analyzed were sex, age, cancer diagnosis, cancer location (digestive tract and genitourinary), nutritional status, including initial weight (IW), at the start of HPN), usual weight (UW) and IW/UW ratio, and body mass index (BMI) at the start of HPN. Performance status was assessed with the KPS scale. Type of catheter used, number of days on HPN and clinical progression of cancer patients were also studied. RESULTS: Data of 41 cancer patients (60.8% female) were evaluated. Mean age at the start of HPN was 60.45 years. Cancer location was digestive tract (n = 36; 87.8%); gynecologic (n = 4; 9.7%), urinary tract (n = 1; 2.4%). Median IW was 55 kg (45; 64) and BMI was 20 (17.58; 22.84). The IW/UW ratio was -15 kg (-20;-10). The catheters used were peripherally inserted central catheter (n = 30; 73.2%), tunneled (n = 9; 22%) and port (n = 2; 4.8%). The median duration of HPN was 72 days (30; 159). The KPS results showed that 16 cancer patients (39%) had KPS scores ≤50, 17 (41.5%) requiring HPN were discharged and 24 (58.5%) died. The association between disease progression and KPS scores ≤50 was significant (p = 0.025; OR (95% CI): 5.28 (1.07; 36.18). CONCLUSION: The KPS scale is a reliable tool to identify cancer patients eligible for HPN. Cancer patients with ≤50 scores had a five-fold increased risk of death than patients with >50 scores.

Care of patients on home parenteral nutrition during the first year of the COVID-19 pandemic: Management of central line-associated bloodstream infections.

BACKGROUND AND AIM: The aim of this study was to analyze central line-associated bloodstream infections (CLABSI) in home parenteral nutrition (HPN) patients assisted by an interdisciplinary team during the first year of the COVID-19 pandemic in Argentina. METHODS: Longitudinal, retrospective and analytical study of patients on HPN for ≥90 days during 2020. Data collection included age (adults >18 years, pediatric ≤18 years), gender, diagnosis, type of catheter, number of lumens, venous access, days on HPN, infusion modality and number of CLABSI-associated events. In COVID-19 cases, number of patients, disease progression, mortality rate and microorganisms involved were analyzed. RESULTS: A total of 380 patients were included, 120 (31.6%) pediatric and 260 (68.4%) adult patients. Median age was 44.50 years (10; 62.25). Twelve patients (3.15% of the total) had COVID-19; of these, two pediatric and seven adult patients had no complications, and three adults died of COVID-19 pneumonia. The diagnoses observed were benign chronic intestinal failure (CIF, n = 311), grouped into short bowel (n = 214, 56.3%), intestinal dysmotility (n = 56, 14.7%), intestinal fistula (n = 20, 5.3%), and extensive small bowel mucosal disease (n = 21, 5.5%); malignant tumors (n = 52, 13.7%); other (n = 17, 4.4%). Total catheter days were 103,702. Median days of PN duration per patient were 366 (176.2, 366). The types of catheters used were tunneled (317 patients, 83.4%); peripherally inserted central (PICC) line (55 patients, 14.5%) and ports (8 patients; 2.1%). A total of 111 CLABSI was registered, with a prevalence of 1.09/1000 catheter days (adult, 0.86/1000 days; pediatric, 1.51/1000 days). The microorganisms identified in infectious events were Gram + bacteria (38, 34.5%); Gram-bacteria (36, 32%); mycotic (10, 9%); polymicrobial (4, 3.6%); negative culture and signs/symptoms of CLABSI (23, 20.3%). The odds ratio between pediatric and adult patients was 2.29 (1.35, 3.90). CONCLUSION: The rate of CLABSI during the COVID-19 pandemic was within the ranges reported by international scientific societies. The risk of CLABSI was higher in pediatric patients, and mortality rate in COVID-19 infected patients was higher than in the general population.

First registry of adult patients with chronic intestinal failure due to short bowel syndrome in Argentina: The RESTORE project.

BACKGROUND: Short bowel syndrome (SBS) is considered a low prevalence disease. In Argentina, no registries are available on chronic intestinal failure (CIF) and SBS. This project was designed as the first national registry to report adult patients with this disease. METHODS: A prospective multicenter observational registry was created including adult patients with CIF/SBS from approved centers. Demographics, clinical characteristics, nutrition assessment, home parenteral nutrition (HPN) management, surgeries performed, medical treatment, overall survival, and freedom from HPN survival were analyzed. RESULTS: Of the 61 enrolled patients, 56 with available follow-up data were analyzed. At enrollment, the mean intestinal length was 59.5 ± 47.3 cm; the anatomy was type 1 (n = 41), type 2 (n = 10), and type 3 (n = 5). At the end of the interim analysis, anatomy changed to type 1 in 31, type 2 in 17, and type 3 in 8 patients. The overall mean time on HPN before enrollment was 33.5 ± 56.2 months. Autologous gastrointestinal reconstruction surgery was performed before enrollment on 21 patients, and afterward on 11. Nine patients (16.1%) were weaned off HPN with standard medical nutrition treatment; 12 patients received enterohormones, and 2 of them suspended HPN; one patient was considered a transplant candidate. In 23.7 ± 14.5 months, 11 of 56 patients discontinued HPN; Kaplan-Meier freedom from HPN survival was 28.9%. The number of cases collected represented 19.6 new adult CIF/SBS patients per year. CONCLUSION: The RESTORE project allowed us to know the incidence, the current medical and surgical approach for this pathology, as well as its outcome and complications at dedicated centers.

Evolución de los parámetros antropométricos de niños con parálisis cerebral asistidos por un equipo especializado en soporte nutricional domiciliario / Evolution of the anthropometric parameters of children with cerebral palsy assisted by a team specialized in home nutritional support

Introducción: los niños con parálisis cerebral (PC) presentan habitualmente compromiso nutricional. Objetivos: evaluar el estado nutricional antropométrico de niños con PC con nutrición enteral (NE) asistidos por un equipo especializado en domicilio. Materiales y métodos: cohorte retrospectiva sobre datos de historia clínica, evaluados durante un año (2018-2019). Se evaluó: z score de .peso (Pz), z score de talla (Tz), z score de índice de masa corporal (IMC) (IMCz). En los que no pudo usarse pediómetro, se utilizó medición de la longitud de la tibia (LT). Se los dividió en: 10 años (Grupo 2). Se excluyeron: síndromes genéticos y/o epilepsia refractaria, y quienes no adhirieron al tratamiento nutricional. Se registraron complicaciones asociadas al tratamiento nutricional. Resultados: se analizaron 72 pacientes, Grupo 1: 38 pacientes; inicio: Tz x -2,85(-4,50;-1,41), Pz x -2,83 (-3,72;-1,59), promedio de IMCz -1,10 (DE 2,25). Final, Tz fue x -2,55 (-3,92; -1,42), el Pz x -2,15 (-3,05;-1,03), promedio IMCz: 0,93 (DE 2,21). Se observó diferencia significativa entre el inicio y el final del período en el Z score peso (p=0,030). En el Grupo 2 se incorporaron 34 pacientes (47%), 22 (64%) de sexo masculino con una mediana de 13,62 de edad (r 11,6-14,83 años). La mediana del Tz fue -3,00 (-3,81; -1,53), el score Pz -2,63 (-3,68; -2,23), la media del IMCz fue -1,75 (DE:1,73). En el final del período observado, la mediana del Tz e -2,84 (-4,13;-1,25), Pz -2,84 (-3,42; -1,83), la media del IMCz fue -1,53 (DE:2,19). Se observaron diferencias significativas entre el inicio y final del período observado en el Pz (p=0,049). No se identificaron complicaciones graves en el período observado (hospitalizaciones, broncoaspiración, fallecimientos). Conclusiones: se observó mejoría del estado nutricional y bajo índice de complicaciones en el período estudiado

Introduction: children with cerebral palsy (CP) usually present nutritional compromise. Objectives: to evaluate the anthropometric nutritional status of children with CP with enteral nutrition (EN) assisted by a specialized team at home. Materials and methods: a retrospective cohort study on clinical report data, evaluated during one year (2018-2019). The following were evaluated: weight z score (Pz), height z score (Tz), BMI z score (BMIz). In those that could not be used a pediometer, measurement of the tibia length (TL) was used. They were divided into: <10 years (Group1) and >10 years (Group2). The following were excluded: genetic syndromes and/or refractory epilepsy, and those who did not adhere to nutritional treatment. Complications associated with nutritional treatment were recorded. Results: 72 patients were analyzed, Group 1: 38 patients: baseline: Tz x -2.85 (-4.50, -1.41), Pz x -2.83 (-3.72, -1.59), BMIz 0,93 (SD 2,21). Final, Tz was x -2.55 (-3.92, -1.42), Pz x -2.15 (-3.05, -1.03), BMI x: 15.95. Significant differences were observed between the start-end in P p<0.001, T p0.001, and Pz p0.030. Group 2: 34 patients, 2018: Tz x -3.00 (-3.81, -1.53), Pz x -2.63 (-3.68, -2.23), BMIz x -1,75 (DE:1,73). Final Tz x -2.84 (-4.13, -1.25), Pz x -2.84 (-3.42,-1.83) BMI -1,53 (DE: 2,19).Significant differences were observed between the beginning and end of the period observed in the Pz (p=0.049). No severe complications were recorded (hospitalizations, bronchial aspiration, death). Conclusions: an improvement in nutritional status and no severe complications were observed in the period studied

Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome: An international multicenter survey.

BACKGROUND AND AIMS: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. METHODS: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. 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 categorized as <1, 1-2, 2-3 and >3 L/day. RESULTS: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. CONCLUSIONS: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.

Postsurgical Intestinal Rehabilitation Using Semisynthetic Glucagon-Like Peptide-2 Analogue (sGLP-2) at a Referral Center: Can Patients Achieve Parenteral Nutrition and sGLP-2 Independency?

BACKGROUND: Teduglutide, a semisynthetic analogue of glucagon-like peptide-2 (sGLP-2), increases intestinal absorption of fluids and nutrients, reducing the need for parenteral nutrition (PN). This report aims to describe our experience with sGLP-2 in a cohort of adult patients with short-bowel syndrome. METHODS: This is a prospective observational study on adult patients initially evaluated in our specialized intestinal rehabilitation program that received sGLP-2 from June 2014 to March 2020. RESULTS: Autologous gastrointestinal reconstruction surgery (AGIRS) was performed in 108 patients; 68.5% (74 of 108) achieved intestinal sufficiency with standard medical therapy. Seventeen patients were treated with sGLP-2; 66.5% (8 of 12) received treatment for a mean time of 25.8 weeks (3.4-54.0) and could suspend PN. One patient reinitiated treatment due to renal lithiasis and acute renal failure. Currently, 7 of 12 patients (53.8%) continue without PN for a mean time of 165.6 weeks. Volume, energy, and days of PN were reduced in all patients. No serious adverse events were registered. Four of 7 patients (57.1%) who discontinued PN could also discontinue sGLP-2. Therefore, the use of sGLP-2 increased the overall success rate of PN independency after AGIRS to 76% (82 of 108). CONCLUSION: This study confirmed that sGLP-2 should be considered as part of the standard therapy for postsurgical medical rehabilitation treatment in patients with chronic intestinal failure. We add to the current knowledge that some patients can discontinue both PN and sGLP-2 in the long term, achieving complete recovery of their quality of life.

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.

Results of Surgical and Medical Rehabilitation for Adult Patients With Type III Intestinal Failure in a Comprehensive Unit Today: Building a New Model to Predict Parenteral Nutrition Independency.

BACKGROUND: Short-bowel syndrome remains the primary cause of intestinal failure (IF) in adult patients. We aim to report the long-term results of medical and surgical rehabilitation in a cohort of patients with type III IF (III-IF) and develop a formula to predict parenteral nutrition (PN) independency. METHODS: We used a retrospective analysis of a prospective database for III-IF patients undergoing autologous gastrointestinal reconstruction surgery (AGIRS) from March 2006 to August 2018. Analyzed variables included demographic data, postsurgical intestinal length (PSIL), postsurgical anatomy, teduglutide (TED) treatment, and PN volume reduction. Univariate analysis, Cox regression, logistic regression forward stepwise models, and receiver operating characteristic (ROC) curve were done using SPSS v20. RESULTS: AGIRS was performed in 88 patients. The most frequent anatomy at first visit was type 1. Prevailing anatomy after surgery was type 3. Eight patients started TED; 6 achieved freedom from PN. At a mean follow-up time of 1606.1 ± 1190.25 days, freedom from PN survival was achieved in 83%. Variables identified at the logistic regression analysis led to a novel formula to predict intestinal rehabilitation, including PSIL, presence of ileocecal valve, and use of TED as part of postsurgical treatment. CONCLUSIONS: AGIRS in this group of patients enabled intestinal length increase and also intestinal anatomy conversion into a more favorable type for intestinal rehabilitation. TED treatment was useful to discontinue PN in patients with classical negative anatomical predictors. The novel predicting formula has an ROC area under the curve = 0.82. Further studies are necessary to validate this formula.

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.

GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community.

BACKGROUND: This initiative aims to build a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: The Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A 2-step approach for the malnutrition diagnosis was selected, that is, first screening to identify at risk status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among GLIM participants that selected 3 phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and 2 etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least 1 phenotypic criterion and 1 etiologic criterion should be present. Phenotypic metrics for grading severity are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSIONS: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The construct should be re-considered every 3-5 years.

[Progression of renal function in patients with chronic kidney disease on a low-protein diet supplemented with aminoacids and ketoanalogues]. / Evolución de la función renal en pacientes con enfermedad renal crónica con dieta restringida en proteínas suplementada con una mezcla de aminoácidos y cetoanálogos.

INTRODUCTION: chronic kidney disease (CKD) is a public health problem. Low-protein diets supplemented with ketoacids and essential aminoacids have proved effective at different CKD stages. AIM: to assess the progression of renal failure in adult patients with CKD stages 3b and 4 receiving a protein-controlled diet supplemented with aminoacids and ketoanalogues. METHODS: retrospective, descriptive intervention study. The nutritional intervention consisted of a protein/calorie intake of 0.4-0.6 g/kg/day and 30-35 kcal/kg/day plus a tablet of ketoanalogues (Ketosteril®)/5 kg weight. We assessed nutritional condition, glomerular filtration (GF) and creatinine, urea and albumin levels at 0, 3, 6, 9 and 12 months. SPSS version 18 was used for data statistical analysis. RESULTS: thirty-three patients were studied (67% male; mean age 59.7 years, r: 24-87). Protein/calorie intake was 0.55 ± 0.20 g/kg/day and 34 ± 4.51 kcal/kg/day. Ketosteril® intake was 11.87 tablets/day (r: 9-14). Initial GF was 24.97 ± 6.64 ml/min/1.73 m2, showing a significant increase between three and 12 months (25.51 ± 8.57 and 29.26 ± 10.33 ml/min/1.73 m2; p = 0.006). Urea nitrogen decreased significantly at six months compared with the initial level (p < 0.005). Body mass index did not change significantly (initial, 26. 63 ± 4.08 kg/m2; after a year, 26.78 ± 3.98 kg/m2). Initial and final albumin levels were 3.53 ± 0.64 g/l and 4.00 ± 0.53 g/l, respectively (p = 0.79). CONCLUSION: a low-protein diet supplemented with ketoanalogues administered to patients with CKD stages 3b and 4 preserved nutritional condition and mineral balance, improved GF significantly and decreased urea levels.

Prescribed hypocaloric nutrition support for critically-ill adults.

BACKGROUND: There are controversies about the amount of calories and the type of nutritional support that should be given to critically-ill people. Several authors advocate the potential benefits of hypocaloric nutrition support, but the evidence is inconclusive. OBJECTIVES: To assess the effects of prescribed hypocaloric nutrition support in comparison with standard nutrition support for critically-ill adults SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, Embase and LILACS (from inception to 20 June 2017) with a specific strategy for each database. We also assessed three websites, conference proceedings and reference lists, and contacted leaders in the field and the pharmaceutical industry for undetected/unpublished studies. There was no restriction by date, language or publication status. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing hypocaloric nutrition support to normo- or hypercaloric nutrition support or no nutrition support (e.g. fasting) in adults hospitalized in intensive care units (ICUs). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We meta-analysed data for comparisons in which clinical heterogeneity was low. We conducted prespecified subgroup and sensitivity analyses, and post hoc analyses, including meta-regression. Our primary outcomes were: mortality (death occurred during the ICU and hospital stay, or 28- to 30-day all-cause mortality); length of stay (days stayed in the ICU and in the hospital); and Infectious complications. Secondary outcomes included: length of mechanical ventilation. We assessed the quality of evidence with GRADE. MAIN RESULTS: We identified 15 trials, with a total of 3129 ICU participants from university-associated hospitals in the USA, Colombia, Saudi Arabia, Canada, Greece, Germany and Iran. There are two ongoing studies. Participants suffered from medical and surgical conditions, with a variety of inclusion criteria. Four studies used parenteral nutrition and nine studies used only enteral nutrition; it was unclear whether the remaining two used parenteral nutrition. Most of them could not achieve the proposed caloric targets, resulting in small differences in the administered calories between intervention and control groups. Most studies were funded by the US government or non-governmental associations, but three studies received funding from industry. Five studies did not specify their funding sources.The included studies suffered from important clinical and statistical heterogeneity. This heterogeneity did not allow us to report pooled estimates of the primary and secondary outcomes, so we have described them narratively.When comparing hypocaloric nutrition support with a control nutrition support, for hospital mortality (9 studies, 1775 participants), the risk ratios ranged from 0.23 to 5.54; for ICU mortality (4 studies, 1291 participants) the risk ratios ranged from 0.81 to 5.54, and for mortality at 30 days (7 studies, 2611 participants) the risk ratios ranged from 0.79 to 3.00. Most of these estimates included the null value. The quality of the evidence was very low due to unclear or high risk of bias, inconsistency and imprecision.Participants who received hypocaloric nutrition support compared to control nutrition support had a range of mean hospital lengths of stay of 15.70 days lower to 10.70 days higher (10 studies, 1677 participants), a range of mean ICU lengths of stay 11.00 days lower to 5.40 days higher (11 studies, 2942 participants) and a range of mean lengths of mechanical ventilation of 13.20 days lower to 8.36 days higher (12 studies, 3000 participants). The quality of the evidence for this outcome was very low due to unclear or high risk of bias in most studies, inconsistency and imprecision.The risk ratios for infectious complications (10 studies, 2804 participants) of each individual study ranged from 0.54 to 2.54. The quality of the evidence for this outcome was very low due to unclear or high risk of bias, inconsistency and imprecisionWe were not able to explain the causes of the observed heterogeneity using subgroup and sensitivity analyses or meta-regression. AUTHORS' CONCLUSIONS: The included studies had substantial clinical heterogeneity. We found very low-quality evidence about the effects of prescribed hypocaloric nutrition support on mortality in hospital, in the ICU and at 30 days, as well as in length of hospital and ICU stay, infectious complications and the length of mechanical ventilation. For these outcomes there is uncertainty about the effects of prescribed hypocaloric nutrition, since the range of estimates includes both appreciable benefits and harms.Given these limitations, results must be interpreted with caution in the clinical field, considering the unclear balance of the risks and harms of this intervention. Future research addressing the clinical heterogeneity of participants and interventions, study limitations and sample size could clarify the effects of this intervention.

Evolución de la función renal en pacientes con enfermedad renal crónica con dieta restringida en proteínas suplementada con una mezcla de aminoácidos y cetoanálogos / Progression of renal function in patients with chronic kidney disease on a low-protein diet supplemented with aminoacids and ketoanalogues

Introducción: la enfermedad renal crónica (ERC) es un problema de salud pública. Se ha evaluado el uso de dietas con bajo contenido proteico suplementadas con cetoácidos y aminoácidos esenciales en diferentes estadios de la ERC. Objetivo: observar la evolución de la función renal durante un año en pacientes adultos con ERC estadios 3b y 4 con dieta controlada en proteínas y suplementada con aminoácidos y cetoanálogos. Métodos: estudio retrospectivo, descriptivo de una intervención. Intervención nutricional: aporte proteico-calórico: 0,4-0,6 g/kg/día y 30-35 kcal/kg/día más un comprimido de alfacetoanálogos (Ketosteril(R))/5 kg de peso. Se evaluaron el estado nutricional, el filtrado glomerular (FG), la creatinemia, la uremia y la albuminemia a los 0, 3, 6, 9 y 12 meses. Se utilizó el programa SPSS versión 18 para el análisis estadístico. Resultados: fueron estudiados 33 pacientes, un 67% de ellos masculinos, con un promedio de edad de 59,7 años (r: 24-87). Aporte proteico-calórico: 0,55 ± 0,20 g/kg/día y 34 ± 4,51 kcal/kg/día. Consumo de Ketosteril(R): 11,87 comprimidos diarios (r: 9-14). FG inicial: 24,97 ± 6,64 ml/min/1,73 m2, con un aumento significativo entre los tres y los 12 meses (25,51 ± 8,57 y 29,26 ± 10,33 ml/min/1,73 m2; p = 0,006). Nitrógeno ureico: disminuyó significativamente a los seis meses respecto del valor inicial (p < 0,005). Índice de masa corporal: sin cambios significativos al inicio (26,63 ± 4,08 kg/m2) y al final (26,78 ± 3,98 kg/m2). Albuminemia: 3,53 ± 0,64 g/l y 4,00 ± 0,53 g/l al inicio y al final (p = 0,079).Conclusión: los pacientes con ERC estadios 3b y 4 tratados con una dieta baja en proteínas y cetoanálogos mantuvieron el estado nutricional y el equilibrio mineral, mejoraron significativamente el FG y disminuyeron la uremia

Introduction: chronic kidney disease (CKD) is a public health problem. Low-protein diets supplemented with ketoacids and essential aminoacids have proved effective at different CKD stages. Aim: to assess the progression of renal failure in adult patients with CKD stages 3b and 4 receiving a protein-controlled diet supplemented with aminoacids and ketoanalogues. Methods: retrospective, descriptive intervention study. The nutritional intervention consisted of a protein/calorie intake of 0.4-0.6 g/kg/day and 30-35 kcal/kg/day plus a tablet of ketoanalogues (KetosterilR)/5 kg weight. We assessed nutritional condition, glomerular filtration (GF) and creatinine, urea and albumin levels at 0, 3, 6, 9 and 12 months. SPSS version 18 was used for data statistical analysis. Results: thirty-three patients were studied (67% male; mean age 59.7 years, r: 24-87). Protein/calorie intake was 0.55 +/- 0.20 g/kg/day and 34 +/- 4.51 kcal/kg/day. KetosterilR intake was 11.87 tablets/day (r: 9-14). Initial GF was 24.97 +/- 6.64 ml/min/1.73 m2, showing a significant increase between three and 12 months (25.51 +/- 8.57 and 29.26 +/- 10.33 ml/min/1.73 m2; p = 0.006). Urea nitrogen decreased significantly at six months compared with the initial level (p < 0.005). Body mass index did not change significantly (initial, 26. 63 +/- 4.08 kg/m2; after a year, 26.78 +/- 3.98 kg/m2). Initial and final albumin levels were 3.53 +/- 0.64 g/l and 4.00 +/- 0.53 g/l, respectively (p = 0.79). Conclusion: a low-protein diet supplemented with ketoanalogues administered to patients with CKD stages 3b and 4 preserved nutritional condition and mineral balance, improved GF significantly and decreased urea levels

Clinical classification of adult patients with chronic intestinal failure due to benign disease: An international multicenter cross-sectional survey.

BACKGROUND & AIMS: The aim of the study was to evaluate the applicability of the ESPEN 16-category clinical classification of chronic intestinal failure, based on patients' intravenous supplementation (IVS) requirements for energy and fluids, and to evaluate factors associated with those requirements. METHODS: ESPEN members were invited to participate through ESPEN Council representatives. Participating centers enrolled adult patients requiring home parenteral nutrition for chronic intestinal failure on March 1st 2015. The following patient data were recorded though a structured database: sex, age, body weight and height, intestinal failure mechanism, underlying disease, IVS volume and energy need. RESULTS: Sixty-five centers from 22 countries enrolled 2919 patients with benign disease. One half of the patients were distributed in 3 categories of the ESPEN clinical classification. 9% of patients required only fluid and electrolyte supplementation. IVS requirement varied considerably according to the pathophysiological mechanism of intestinal failure. Notably, IVS volume requirement represented loss of intestinal function better than IVS energy requirement. A simplified 8 category classification of chronic intestinal failure was devised, based on two types of IVS (either fluid and electrolyte alone or parenteral nutrition admixture containing energy) and four categories of volume. CONCLUSIONS: Patients' IVS requirements varied widely, supporting the need for a tool to homogenize patient categorization. This study has devised a novel, simplified eight category IVS classification for chronic intestinal failure that will prove useful in both the clinical and research setting when applied together with the underlying pathophysiological mechanism of the patient's intestinal failure.

Glutathione S-transferase gene polymorphisms in celiac disease and their correlation with genomic instability phenotype.

BACKGROUND AND OBJECTIVE: Genomic instability and reduced glutathione S-transferase (GST) activity have been identified as potential risk factors for malignant complications in celiac disease (CD). In this study, we assessed the possible influence of GST polymorphisms on genome instability phenotypes in a genetically characterised group of celiac patients from previous studies. METHODS: The deletion polymorphisms in GSTM1 and GSTT1 genes and the single-nucleotide polymorphism GSTP1 c.313A>G were genotyped using PCR in a set of 20 untreated adult patients with a known genomic instability phenotype and 69 age- and sex-matched healthy individuals. RESULTS: The frequencies of variant genotypes in patients were GSTM1-null (30%), GSTT1-null (5%), GSTP1-AG (60%) and GSTP1-GG (15%), and they showed no differences from controls. No significant differences were found in the genotype distribution based on telomere length. Cases with GSTM1-null genotype (83%) and microsatellite stability were more frequent than those with genomic instability. Moreover, carriers of GSTP1-variant genotype (73%) and stable phenotype were significantly increased compared to unstable patients (27%) (P=0.031). No differences were found according to the clinical-pathological characteristics of celiac cases. CONCLUSIONS: No association between GST polymorphic variants and celiac-associated genomic instability was proven in our cohort. Future studies should explore the usefulness of other biomarkers to distinguish celiac patients who are susceptible to cancer development.

Risk of fracture in celiac disease: gender, dietary compliance, or both?

AIM: To determine the incidence of peripheral fractures in patients with celiac disease (CD) and the effect of treatment on fracture risk. METHODS: We compared the incidence and risk of peripheral fractures before and after diagnosis between a cohort of 265 patients who had been diagnosed with CD at least 5 years before study entry and a cohort of 530 age- and sex-matched controls who had been diagnosed with functional gastrointestinal disorders. Data were collected through in-person interviews with an investigator. The overall assessment window for patients was 9843 patient-years (2815 patient-years after diagnosis). RESULTS: Compared with the control group, the CD cohort showed significantly higher incidence rate and risk of first peripheral fracture before diagnosis [adjusted hazard ratio (HR): 1.78, 95% CI: 1.23-2.56, P < 0.002] and in men (HR: 2.67, 95% CI: 1.37-5.22, P < 0.004). Fracture risk was significantly associated with the classic CD presentation with gastrointestinal symptoms (P < 0.003). In the time period after diagnosis, the risk of fractures was comparable between the CD cohort and controls in both sexes (HR: 1.08, 95% CI: 0.55-2.10 for women; HR: 1.57, 95% CI: 0.57-4.26 for men). CONCLUSION: CD patients have higher prevalence of fractures in the peripheral skeleton before diagnosis. This is associated with male sex and classic clinical presentation. The fracture risk was reduced after the treatment.

Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable?

AIM: To establish the diagnostic performance of several serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential serological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.

A prospective evaluation of endoscopic markers for identifying celiac disease in patients with high and low probability of having the disease.

BACKGROUND/OBJECTIVES: the usefulness of duodenoscopic markers for predicting celiac disease (CD) has been questioned. We assessed the diagnostic efficacy of endoscopic markers of mucosal atrophy in individuals with different pretest probability of CD. METHODS: we prospectively performed endoscopic intestinal biopsies and CD-related serology tests in 661 individuals, including 143 consecutive patients attending a malabsorption clinic (high pretest probability) and 518 subjects randomly selected fom those undergoing routine endoscopy because of upper GI symptoms (low pretest probability). Duodenoscopic markers reported were: mosaic pattern, scalloped folds, and reduction in number or loss of Kerkring's folds. RESULTS: sixty-three (44.1%) and 18 (3.5%) patients were diagnosed with CD in the high and low risk groups, respectively Among high pretest subjects, the presence of any marker had very high sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the identification of CD (92.1%, 93.8%, 92.1%, 93.8% and 93.0%, respectively). The performance of these parameters for the presence of any marker in the low pretest population were 61.1%, 96.8%, 40.7%, 98.6% and 95.6%, respectively. Sensitivity (p < 0.004) and positive predictive value (p < 0.0001) of markers were significantly higher for the high risk patients. The identification of a reduction in number or loss of Kerkring'sfolds was not a reliable finding unless other signs were also present. CONCLUSIONS: we confirm that endoscopic markers are useful in predicting CD in different clinical scenarios. The high negative predictive value in the low probability group suggests that intestinal biopsy is not required if endoscopic markers are absent.

Analysis of genomic instability in adult-onset celiac disease patients by microsatellite instability and loss of heterozygosis.

BACKGROUND AND AIMS: Malignant complications of celiac disease (CD) include carcinomas and lymphomas. The genetic basis behind cancer development in CD is not known, but acquisition of genetic abnormalities and genomic instability has been involved. The aim of this study was to explore molecular characteristics of genomic instability in CD patients by analyzing microsatellite instability (MSI) and loss of heterozygosis (LOH) with carefully selected microsatellites. METHODS: We genotyped small bowel biopsies and peripheral blood samples from 20 untreated CD patients using five microsatellites related to MMR genes (panel A), and five repeats associated with tumor suppressor genes, chromosome instability, inflammation, and cancer (panel B). RESULTS: Genomic instability was found in seven out of 20 (35%) cases at: D5S107, D18S58, GSTP, TP53 or DCC, being TP53 the most frequently affected (five out of seven cases; 71%). Microsatellite alterations were significantly found using panel B markers (P=0.04). No cases with high frequency of MSI and replication error phenotype were detected. Only one case displayed MSI-L alone. Three patients exhibited LOH and three other cases showed LOH with low level of MSI, being classified as having chromosome instability phenotype. CONCLUSION: Two novel observations were found in this study: first, the finding that non-neoplastic cells from a group of untreated CD patients present genomic instability at nucleotide level; and second, the advantage to use carefully selected microsatellites to identify celiac patients with molecular instability. Our data support the existence of chromosome instability phenotype in CD, suggesting that stable and unstable patients are genomically distinct subtypes that may follow a different evolution.