Nutrition in the Intensive Care Unit-A Narrative Review.

BACKGROUND: While consent exists, that nutritional status has prognostic impact in the critically ill, the optimal feeding strategy has been a matter of debate. METHODS: Narrative review of the recent evidence and international guideline recommendations focusing on basic principles of nutrition in the ICU and the treatment of specific patient groups. Covered topics are: the importance and diagnosis of malnutrition in the ICU, the optimal timing and route of nutrition, energy and protein requirements, the supplementation of specific nutrients, as well as monitoring and complications of a Medical Nutrition Therapy (MNT). Furthermore, this review summarizes the available evidence to optimize the MNT of patients grouped by primarily affected organ system. RESULTS: Due to the considerable heterogeneity of the critically ill, MNT should be carefully adapted to the individual patient with special focus on phase of critical illness, metabolic tolerance, leading symptoms, and comorbidities. CONCLUSION: MNT in the ICU is complex and requiring an interdisciplinary approach and frequent reevaluation. The impact of personalized and disease-specific MNT on patient-centered clinical outcomes remains to be elucidated.

A prospective trial to evaluate treatment effects of a ß-hydroxy-ß-methylbutyrate containing nutrient for leakage at the anastomotic site after esophagectomy.

Anastomotic leakage after esophagectomy is associated with prolonged hospitalization and increased medical cost. Additionally, it sometimes leads to a fatal condition and impaired postoperative quality of life. During the process of wound healing, ß-hydroxy-ß-methylbutyrate (HMB) is important for collagen biosynthesis. An open-label prospective intervention trial has been designed to evaluate the treatment effect of an enteral nutrient containing HMB with arginine and glutamine (Abound, Abbott Japan Co., Ltd.) for leakage at the anastomotic site after esophagectomy. Patients in whom leakage at the anastomotic site developed within 14 days after esophagectomy are eligible and Abound (24 g) is administered for 14 days through an enteral feeding tube. The target sample size is 10. The primary endpoint is duration between diagnosis and cure of leakage. Surgical procedure, safety, length of fasting, drainage placement and hospital stay, and nutritional status are determined as secondary endpoints. A historical control consisting of 20 patients who had leakage at the anastomotic site after esophagectomy between 2005 and 2018 at Nagoya University Hospital is compared with enrolled patients.

Helicobacter pylori antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage.

Infection with Helicobacter pylori causes chronic inflammation and is a risk factor for gastric cancer. Antibiotic treatment or increased dietary folate prevents gastric carcinogenesis in male INS-GAS mice. To determine potential synergistic effects, H. pylori-infected male INS-GAS mice were fed an amino acid defined (AAD) diet with increased folate and were treated with antibiotics after 18 weeks of H. pylori infection. Antibiotic therapy decreased gastric pathology, but dietary folate had no effect. However, the combination of antibiotics and the AAD diet induced anemia, gastric hemorrhage, and mortality. Clinical presentation suggested hypovitaminosis K potentially caused by dietary deficiency and dysbiosis. Based on current dietary guidelines, the AAD diet was deficient in vitamin K. Phylloquinone administered subcutaneously and via a reformulated diet led to clinical improvement with no subsequent mortalities and increased hepatic vitamin K levels. We characterized the microbiome and menaquinone profiles of antibiotic-treated and antibiotic-free mice. Antibiotic treatment decreased the abundance of menaquinone producers within orders Bacteroidales and Verrucomicrobiales. PICRUSt predicted decreases in canonical menaquinone biosynthesis genes, menA and menD. Reduction of menA from Akkermansia muciniphila, Bacteroides uniformis, and Muribaculum intestinale were confirmed in antibiotic-treated mice. The fecal menaquinone profile of antibiotic-treated mice had reduced MK5 and MK6 and increased MK7 and MK11 compared to antibiotic-free mice. Loss of menaquinone-producing microbes due to antibiotics altered the enteric production of vitamin K. This study highlights the role of diet and the microbiome in maintaining vitamin K homeostasis.

Clinical Effects of a Pectin-Containing Oligomeric Formula in Tube Feeding Patients: A Multicenter Randomized Clinical Trial.

BACKGROUND: A pectin-containing oligomeric formula (POF) is a unique type of enteral formula that transforms from a liquid to a gel after reacting with gastric acid. Reports on its clinical effects have been limited. The present study was conducted to examine and verify the clinical effects of POF. METHODS: The study subjects were 201 stable patients receiving intragastric tube feeding. They were randomized into 2 groups to receive either POF or a standard polymeric formula (SPF) as a control. The duration of observation was 1 week. Analyses were conducted for the incidence of predefined composite events, including diarrhea, defecation treatments, and other enteral nutrition (EN) management-related events. RESULTS: Composite events occurred in 15 of 98 patients in the POF group and 30 of 100 patients in the SPF group, with a significantly lower incidence in the POF group compared with the SPF group (P = 0.011). In particular, diarrhea occurred in 2 patients in the POF group and 13 patients in the SPF group, with a significantly lower incidence in the POF group compared with the SPF group (P = 0.003). CONCLUSIONS: The results of this study suggest that POF is less likely to cause EN-related events, especially diarrhea, than SPF is.

Oligomeric Enteral Nutrition in Undernutrition, due to Oncology Treatment-Related Diarrhea. Systematic Review and Proposal of An Algorithm of Action.

Oncology treatment-related diarrhea and malnutrition appear together in oncological patients because of the disease itself, or the treatments that are administered for it. Therefore it is essential to carry out a nutritional treatment. Enteral nutrition formulas, containing peptides and medium chain triglycerides, can facilitate absorption in cases of malabsorption. There are few references to the use of enteral nutrition in the clinical society guidelines of patient management with oncology treatment-related diarrhea (OTRD). A bibliographic review of the studies with oligomeric enteral nutrition in OTRD found only nine studies with chemotherapy (all with the same oligomeric formula in which oral mucositis improves, while the rest of the outcomes show different results), and eight studies with radiotherapy (with different products and very heterogeneous results). We hereby present our action algorithm to supplement the diet of OTRD patients with an oligomeric enteral nutrition formula. The first step is the nutritional assessment, followed by the assessment of the functional capacity of the patient's intestine. With these two aspects evaluated, the therapeutic possibilities available vary in degrees of complexity: These will range from the usual dietary recommendations, to supplementation with oral oligomeric enteral nutrition, along with complete enteral nutrition with oligomeric formula, and up to potentially total parenteral nutrition.

Hepatoprotective Effect of Jianpi Huoxue Formula on Nonalcoholic Fatty Liver Disease Induced by Methionine-Choline-Deficient Diet in Rat.

In parallel with the prevalence metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in most countries. It features a constellation of simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even hepatocellular carcinoma. There are no approved drugs for effective management of NAFLD and NASH. Jianpi Huoxue formula (JPHX) mainly consists of Atractylodes macrocephal (Baizhu), Salvia miltiorrhiza (Danshen), Rasux Paeonia Alba (Baishao), Rhizoma Alismatis (Zexie), and Fructus Schisandrae Chinensis (Wuweizi), which may have beneficial effects on NAFLD. The aim of the study was to identify the effect of JPHX on NAFLD. A NAFLD model was induced by methionine-choline-deficient food (MCD) in Wistar rats and orally administered with simultaneous JPHX, once a day for 8 weeks. Hepatocellular injury, lipid profile, inflammation, fibrosis, and apoptosis were evaluated. The results showed that JPHX significantly decreased the abnormal serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the MCD model (P<0.05). Furthermore, JPHX protected MCD diet-fed rats from accumulation of hepatic triglycerides (TG) and total cholesterol (TC). Histological examination demonstrated that JPHX noticeably normalized the NAFLD activity score (NAS). Moreover, JPHX ameliorated liver inflammation by decreasing TNF-α levels and reduced collagen and matrix metalloproteinases in MCD diet-fed rats. In addition, JPHX prevented rats from MCD-induced cellular apoptosis, as suggested by TUNEL staining, and suppressed the activation of caspase 3 and 7 proteins. JPHX also inhibited the phosphorylation of JNK. In conclusion, JPHX exhibited a hepatoprotective effect against NAFLD in an MCD experimental model.

Nutritional hypophosphatemic rickets secondary to Neocate® use.

Elemental formula is commonly used in children with feeding intolerance. We describe two, medically complex and feeding tube dependent, patients exclusively fed with Neocate® who subsequently developed hypophosphatemic rickets. Both patients had gross motor decline and pain with physical touch. They were found to have low serum phosphorus, normal calcium, and vitamin D studies, with elevated alkaline phosphatase suggestive of nutritional hypophosphatemia. Both courses were complicated by hypocalcemia following formula change and phosphorus supplementation, highlighting the need for careful management of phosphate repletion in affected individuals. Diligent serial electrolyte monitoring as well as attention to bone health is needed in conjunction with elemental nutrition. Formula change led to restoration of calcium and phosphorus homeostasis and radiographic improvement in these patients.

Chronic dietary changes in n-6/n-3 polyunsaturated fatty acid ratios cause developmental delay and reduce social interest in mice.

Polyunsaturated fatty acids (PUFAs) are one of the main cellular building blocks, and dietary changes in PUFA composition are proposed as a potential route to influence brain development. For example, initial studies indicated that there is a relation between blood omega-6(n-6)/omega-3(n-3) PUFA ratios and neurodevelopmental disease diagnosis. To study the consequences of dietary n-6/n-3 PUFA ratio changes, we investigated the impact of a n-3 supplemented and n-3 deficient diet in developing BTBR T + Itpr3tf/J (BTBR) - a mouse inbred strain displaying Autism Spectrum Disorder (ASD)-like symptomatology - and control C57BL/6J mice. This study showed that pre- and postnatal changed dietary n-6/n-3 ratio intake has a major impact on blood and brain PUFA composition, and led to delayed physical development and puberty onset in both strains. The PUFA induced developmental delay did not impact adult cognitive performance, but resulted in reduced social interest, a main ASD behavioral feature. Thus, both chronic dietary n-3 PUFA supplementation and depletion may not be beneficial.

The Addition of Xanthan Gum to Enteral Nutrition Suppresses Postprandial Glycemia in Humans.

The semi-solidified nutrition supplemented with soluble dietary fiber, xanthan gum (XG), inhibited postprandial glycemia in rats. The purpose of the present study is to examine whether XG exerts the same effects in humans. Subjects fasted for 12 h and then ingested the enteral nutrient, Meibalance with or without XG at 9 AM. Blood glucose levels were measured 0, 20, 40, 60, and 120 min after its ingestion. Postprandial blood glucose levels were lower in the XG group than in the control group. At 20 min, postprandial blood glucose levels were significantly lower in the XG group (84±5.3 mg/dL) than in the control group (107±7.8 mg/dL) (p<0.05). A significant difference was also observed in ΔAUC between the two groups. These results demonstrate that XG exerts inhibitory effects on glucose excursion in humans.

Use of standard enteral formula versus enteric formula with prebiotic content in nutrition therapy: A randomized controlled study among neuro-critical care patients.

OBJECTIVE: To compare use of standard enteral formula versus enteric formula with prebiotic content in terms of nutrition therapy related outcomes among neurocritical care patients. METHODS: A total of 46 adult neurocritical care patients who received nutrition therapy with standard enteral formula (SEF group; n = 23) or enteral formula with prebiotic content (EFPC group; n = 23) during their hospitalization in intensive care unit (ICU) were included in this prospective randomized controlled study. Data on patient demographics (age, gender), diagnosis, co-morbid diseases, anthropometrics, length of stay (LOS) in hospital and ICU, Nutritional Risk Screening (NRS-2002) score, and Acute Physiology and Chronic Health (APACHE-II) score were recorded at enrollment. Data on daily nutritional intake [total energy (kcal/day), carbohydrate (g/day), protein (g/day), lipid (g/day), FOS (g/day), enteral volume (ml/day), fluid in enteral product (ml/day) and fluid intake (ml/day)], achievement of target dose [total fluid intake in enteral product (ml)/20 h], laboratory findings (blood biochemistry and complete blood count), complications and drug treatments were recorded on Day 1, Day 4, Day 7, Day 14 and Day 21 of nutrition therapy in SEF and EFPC groups. RESULTS: Use of EFPC compared to SEF was associated with significantly higher total energy, carbohydrate, protein, lipid, enteral volume and fluid intake (p values ranged from <0.05 to <0.001) on each day of nutrition therapy. Target dose was achieved by majority of patients (86.9%) and at day 4 of nutrition therapy in most of patients (71.7%) in the overall study population. Patients in the EFPC group had a non-significant tendency for higher rate (95.7% vs. 78.3%) and earlier (87.0% vs. 56.5% on day 4) achievement of target dose, lower rate (8.7% vs. 56.5%) and faster amelioration (none vs. 52.2% were diarrheic on day 7) of diarrhea and lesser need for insulin (56.5% vs. 13.0%, p = 0.002). Nutrition therapy was associated with significant decrease in prealbumin (Day 14 vs. Day 1, p < 0.05 for both), albumin (Day 14 vs. day 1, p < 0.01 for SEF, p < 0.05 for PEF), hemoglobin (Day 14 and Day 21 vs. Day 1and Day 14 vs. Day 4, p < 0.001 for each for SEF, Day 7, Day 14 and Day 21 vs. Day 1, p < 0.01 for each for PEF) and hematocrit (Day 14 and Day 21 vs. Day 1, p < 0.001 for each for both) levels in both SEF and EFPC groups. CONCLUSIONS: In conclusion, our findings revealed achievement of target nutritional intake in majority of neurocritical care patients via nutrition therapy, whereas EFPC was associated with a non-significant tendency for more frequent and earlier achievement of target dose along with significantly lower rate and faster amelioration of diarrhea as compared with SEF group. Prealbumin and albumin levels remained below the normal range, whereas C reactive protein (CRP) and white blood cell (WBC) were over the normal range throughout the nutrition period in both groups, while creatinine and urea levels were higher in EFPC than in SEF group. Hence, our findings seem to emphasize the importance of avoiding protein debt in provision of nutrition therapy and the likelihood of deterioration of nutritional status in elderly neurocritical care patients despite provision of early enteral nutrition support due to complex and deleterious inflammatory and metabolic changes during critical illness.

Eficacia y tolerancia terapéutica de la D-manosa (2 g) de liberación prolongada 24 horas (asociada a proantocianidinas), frente a proantocianidinas aisladas en el manejo de una serie de mujeres con infecciones urinarias recurrentes / Efficacy and safety of D-mannose (2 g), 24h prolonged release, associated with Proanthocyanidin (PAC), versus isolate PAC, in the management of a series of women with recurrent urinary infections

Objetivo: Comparar la eficacia y seguridad de un complemento alimenticio (Manosar®) (2 gramos de D-manosa, 140 mg de PAC y 7,98 mg de ácido ursólico junto con las vitaminas A, C y E, y el oligoelemento Zinc) en la recurrencia de la ITU y su comparación con un compuesto basado con 240 mg proantocianidinas (PAC aislado), con una duración de administración esperada de 24 semanas. Métodos: Estudio experimental multicéntrico, aleatorizado y doble ciego. Aprobado por el Comité Ético de Investigación clínica del "Complejo Hospitalario de Toledo". Todos los pacientes firmaron el consentimiento. Se incluyeron 150 mujeres con historia de ITU recurrentes sin evidencias de complicación. Se obtuvieron datos válidos de 93 pacientes con edad media de 47,62 años. 42 recibieron Manosar y 51 PAC aislado. Controles cada 30 días durante 6 meses. La confirmación del episodio clínico previo de ITU fue definido al menos por la sintomatología clínica y tira de orina Combur (positiva a leucocito-esterasa y/o nitritos). La confirmación del nuevo episodio incidente durante el estudio fue confirmado por la sintomatología clínica, tira de orina y urinocultivo. Resultados: 33 pacientes (35,48%) padecieron una ITU durante el periodo de 6 meses de seguimiento. En el grupo tratado con Manosar® se observó ITU a los seis meses en un 23,8%, mientras que en el grupo control (PAC aislado) fue de 45,1% (p<0,05). El tiempo libre de enfermedad fue de 78,81 días en el grupo control (PAC aislado) y de 94,7 días en el grupo tratado con Manosar®. Se observó una baja incidencia de acontecimientos adversos, siendo la diarrea el más frecuente en ambos grupos. Conclusión: La toma oral de Manosar®, un sobre al día, es más eficaz que la toma oral de 240 mg de PAC aislado, un sobre al día, en la prevención de las infecciones urinarias de repetición en la mujer (AU)

Objetive: To compare the efficacy and safety of dietary supplement "Manosar®" composed of D-mannose (2 g), 24 h prolonged release, associated with Proanthocyanidin (PAC) (140 mg), ursolic acid (7.98 mg), A, C, and D vitamins and the oligoelement zinc, versus 240 mg of PAC in recurrent urinary tract infections (UTI), for a designed follow-up of 24 weeks, in women. Methods: A multicenter randomized experimental double-blind study was carried out. The study was approved by review board of "Complejo Hospitalario de Toledo" (Spain), and all patients gave informed consent. A total of 150 women with non complicated UTI were screened for participation. Valid data was obtained from 93, with mean age of 48 years. Fortyfour patients were assigned to the Manosar® group and 51 patients to the PAC group. Patients were followed during six months. A previous UTI was defined based on a combination of symptoms and a positive reactive urine trip. Confirmation of a new UTI was based on symptoms, reactive urine strip and urine culture. Results: Thirty-three patients (35%) had an UTI during the six months follow-up. The percentage of UTI of the Manosar® group during this period was 24%, while the percentage of the PAC group was 45% (p<0.05). The disease-free time for the Manosar® group was 95 days, while this time was 79 days for the PAC group. The incidence of side effects was low. Diarrhea was the most frequent side-effect in both groups. Conclusion: Manosar® (oral once a day) is more effective than single dose PAC (240 mg daily orally) to prevent recurrent UTI in women (AU)

Specific protein supplementation using soya, casein or whey differentially affects regional gut growth and luminal growth factor bioactivity in rats; implications for the treatment of gut injury and stimulating repair.

Modulation of regional growth within specific segments of the bowel may have clinical value for several gastrointestinal conditions. We therefore examined the effects of different dietary protein sources on regional gut growth and luminal growth factor bioactivity as potential therapies. Rats were fed for 14 days on isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which is known to cause gut atrophy), ED supplemented with casein or whey or a soya protein-rich feed. Effects on regional gut growth and intraluminal growth factor activity were then determined. Despite calorie intake being similar in all groups, soya rich feed caused 20% extra total body weight gain. Stomach weight was highest on soya and casein diets. Soya enhanced diet caused greatest increase in small intestinal weight and preserved luminal growth factor activity at levels sufficient to increase proliferation in vitro. Regional small intestinal proliferation was highest in proximal segment in ED fed animals whereas distal small intestine proliferation was greater in soya fed animals. Colonic weight and proliferation throughout the colon was higher in animals receiving soya or whey supplemented feeds. We conclude that specific protein supplementation with either soya, casein or whey may be beneficial to rest or increase growth in different regions of the bowel through mechanisms that include differentially affecting luminal growth factor bioactivity. These results have implications for targeting specific regions of the bowel for conditions such as Crohn's disease and chemotherapy.

Leaves of Cordia boissieri A. DC. as a potential source of bioactive secondary metabolites for protection against metabolic syndrome-induced in rats.

Cordia boissieri A. DC. (Boraginaceae) is traditionally used as an herbal remedy for diabetes by Hispanic women in Southwestern USA. A recent investigation showed the significant protective effect of ethyl acetate extract against metabolic syndrome (MS). However, the corresponding active principles responsible for this effect and relations between their structure and biological actions remain unclear. Thus, ethyl acetate extract was subjected to column chromatography, which yielded seven compounds identified on the basis of spectroscopic data as rutin, hesperidin, kaempferol-3-O-ß-d-glucopyranoside, rosmarinic acid, ß-sitosterol-3-O-ß-d-glucopyranoside, quercetin, and kaempferol. The isolated compounds (5 mg/kg/day) were tested in a fructose enriched-diet rat model using metformin as a standard drug. Blood samples were withdrawn for estimation of MS-associated biomarkers and liver samples were subjected to histopathological and immunohistochemical examination. The isolated compounds impaired most of the changes associated with MS as evidenced by improved insulin sensitivity, glucose tolerance, kidney function, lipid profiles and reduced oxidative stress and inflammation by different degrees. It is worth noting that quercetin and kaempferol showed the most potent effect. Structure-activity relationship study revealed that the presence of 2,3-double bond in ring C and ortho-hydroxylation in ring B increases the flavonoids activity while glycosylation or methylation decreased this activity.

Effects on Weight, Blood Lipids, Serum Fatty Acid Profile and Coagulation by an Energy-Dense Formula to Older Care Residents: A Randomized Controlled Crossover Trial.

OBJECTIVES: Dietary intake in frail old adults is often lower than estimated needs. The aim of this study was to evaluate the effects of an energy-dense oral supplement on nutritional status, food intake, and physical function in residents living in care residential homes. DESIGN: Randomized controlled intervention trial with a crossover design. SETTING: Five care residential homes in the southern Stockholm area. PARTICIPANTS: Older people living at care residential homes: age 65 or older, malnourished or at risk of malnutrition according to Mini Nutritional Assessment-Short Form (MNA-SF). INTERVENTION: Energy-dense formula (oleic and linoleic acid emulsion enriched with protein and micronutrients) (Calogen Extra, Nutricia) 30 mL distributed 3 times daily for 6 weeks. MEASUREMENTS: Body weight, 3-day food and fluid record, appetite rating, and physical function (ie, Short Physical Performance Battery, grip strength, and peak expiratory flow). Biochemical indicators of nutritional status, blood lipids, and serum phospholipid fatty acid (FA) profile. RESULTS: Twenty-eight participants completed the 2 phases of the crossover study; group A (n = 14, 87 ± 6 years, 50% women) and group B (n = 14, 82 ± 8 years, 71% women). The intervention periods combined resulted in significantly (P < .05) increased energy intake (238 ± 544 kcal), weight gain (1.4 ± 3.7 kg), improved appetite, relative reduction of saturated FA and increase in polyunsaturated FA, increased apoliporotein A, and reduced serum fibrinogen (-0.9 ± 1.5 g/L). CONCLUSION: Distribution of an oleic and linoleic acid based fat emulsion enriched with protein and micronutrients (Calogen Extra) 3 times daily to old people in care residential homes improved nutritional status, had positive effects on fatty acid profile and blood lipids, and a potential antithrombotic effect. CLINICALTRIALS. GOV IDENTIFIER: NCT01259999.

Developing food supplements for moderately malnourished children: lessons learned from ready-to-use therapeutic foods.

Ready-to-use therapeutic foods (RUTFs) are solid foods that were developed by changing the formulation of the existing liquid diet, F-100, recommended by the World Health Organization (WHO) for the rapid catch-up phase of the treatment of children suffering from severe acute malnutrition (SAM). The resulting products proved highly effective in promoting weight gain in both severely and moderately wasted children and adults, including those infected with HIV. The formulation of the existing RUTFs, however, has never been optimized to maximize linear growth, vitamin and mineral status, and functional outcomes. The high milk content of RUTFs makes it an expensive product, and using lower quantities of milk seems desirable. However, the formulation of alternative, less expensive but more effective versions of RUTF faces difficult challenges, as there are uncertainties regarding the effect in terms of protein quality, antinutrient content, and flatulence factors that will result from the replacement of current dairy ingredients by less expensive protein-rich ingredients. The formulation of alternative RUTFs will require further research on these aspects, followed by efficacy studies comparing the future RUTFs to the existing formulations.

A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: a randomized trial.

BACKGROUND: Trials on specific nutritional supplements for the treatment of pressure ulcers (PUs) have been small, inconsistent in their formulations, or unsuccessful in controlling for total supplement calorie or protein content. OBJECTIVE: To evaluate whether supplementation with arginine, zinc, and antioxidants within a high-calorie, high-protein formula improves PU healing. DESIGN: Multicenter, randomized, controlled, blinded trial. (ClinicalTrials.gov: NCT01107197). SETTING: Long-term care and home care services. PATIENTS: 200 adult malnourished patients with stage II, III, and IV PUs. INTERVENTIONS: An energy-dense, protein-rich oral formula enriched with arginine, zinc, and antioxidants (400 mL/d) or an equal volume of an isocaloric, isonitrogenous formula for 8 weeks. MEASUREMENTS: The primary end point was the percentage of change in PU area at 8 weeks. Secondary end points included complete healing, reduction in the PU area of 40% or greater, incidence of wound infections, the total number of dressings at 8 weeks, and the percentage of change in area at 4 weeks. RESULTS: Supplementation with the enriched formula (n = 101) resulted in a greater reduction in PU area (mean reduction, 60.9% [95% CI, 54.3% to 67.5%]) than with the control formula (n = 99) (45.2% [CI, 38.4% to 52.0%]) (adjusted mean difference, 18.7% [CI, 5.7% to 31.8%]; P = 0.017). A more frequent reduction in area of 40% or greater at 8 weeks was also seen (odds ratio, 1.98 [CI, 1.12 to 3.48]; P = 0.018). No difference was found in terms of the other secondary end points. LIMITATION: Participation was restricted to patients who were malnourished, were able to drink oral supplements, and were living in long-term care institutions or receiving home care services. CONCLUSION: Among malnourished patients with PU, 8 weeks of supplementation with an oral nutritional formula enriched with arginine, zinc, and antioxidants improved PU healing. PRIMARY FUNDING SOURCE: Azienda Ospedaliera Universitaria Maggiore della Carità.

Assessing copper status in pediatric patients receiving parenteral nutrition.

BACKGROUND: Copper is a trace mineral essential for numerous physiological processes. The purpose of this article is to provide data on copper levels in pediatric patients receiving parenteral nutrition (PN) that are useful to guide supplementation in PN formulation. METHOD: This is a retrospective review of hospitalized pediatric patients receiving PN supplemented and not supplemented with copper. In total, 751 supplemented pediatric patients and 90 pediatric patients not supplemented had serum copper levels measured. We assessed patient demographics, days on PN before copper level was drawn, serum copper levels, conjugated bilirubin levels, and C-reactive protein (CRP). RESULTS: The mean serum copper level was 80 mcg/dL at 20 days for supplemented patients and 64 mcg/dL at 14 days for the 90 nonsupplemented patients (P = .0002). In the supplemented patients, 50% of the levels were low and 45% were within the normal range. The remaining 5% of patients had high levels. In nonsupplemented patients, 71% were low and 29% within the normal range. There was no correlation between copper levels and conjugated bilirubin <2 mg/dL and >2 mg/dL (P = .3421). Copper levels correlated with CRP for CRP >4 mg/dL (P = .03). CONCLUSION: Pediatric patients receiving PN should be supplemented with copper to prevent deficiency. Serum copper levels should be assessed at 14 days. Assessment of copper status should not be determined by conjugated bilirubin levels. Serum copper levels may be elevated in patients with acute inflammation and may be falsely elevated when CRP is >4 mg/dL.

Specially formulated foods for treating children with moderate acute malnutrition in low- and middle-income countries.

BACKGROUND: Moderate acute malnutrition, also called moderate wasting, affects around 10% of children under five years of age in low- and middle-income countries. There are different approaches to addressing malnutrition with prepared foods in these settings; for example, providing lipid-based nutrient supplements or blended foods, either a full daily dose or in a low dose as a complement to the usual diet. There is no definitive consensus on the most effective way to treat children with moderate acute malnutrition. OBJECTIVES: To evaluate the safety and effectiveness of different types of specially formulated foods for children with moderate acute malnutrition in low- and middle-income countries, and to assess whether foods complying or not complying with specific nutritional compositions, such as the WHO technical specifications, are safe and effective. SEARCH METHODS: In October 2012, we searched CENTRAL, MEDLINE, LILACS, CINAHL, BIBLIOMAP, POPLINE, ZETOC, ICTRP, mRCT, and ClinicalTrials.gov. In August 2012, we searched Embase. We also searched the reference lists of relevant papers and contacted nutrition-related organisations and researchers in this field.     SELECTION CRITERIA: We planned to included any relevant randomised controlled trials (RCTs), controlled clinical trials (CCTs), controlled before-and-after studies (CBAs), and interrupted time series (ITS) that evaluated specially formulated foods for the treatment of moderate acute malnutrition in children aged between six months and five years in low- and middle-income countries. DATA COLLECTION AND ANALYSIS: Two authors assessed trial eligibility and risk of bias, and extracted and analysed the data. We summarised dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses using the random-effects model and assessed heterogeneity. The quality of evidence was assessed using GRADE methods. MAIN RESULTS: Eight randomised controlled trials, enrolling 10,037 children, met our inclusion criteria. Seven of the trials were conducted in Africa. In general, the included studies were at a low risk of bias. There may have been a risk of performance bias as trial participants were aware which intervention group they were in, but we did not consider this likely to have biased the outcome measurement. We were unable to assess the risk of reporting bias in half of the trials and two trials were at high risk of attrition bias. Any specially formulated food versus standard care - the provision of food increased the recovery rate by 29% (RR 1.29, 95% CI 1.20 to 1.38; 2152 children, two trials; moderate quality evidence), decreased the number dropping out by 70% (RR 0.30, 95% CI 0.22 to 0.39; 1974 children, one trial; moderate quality evidence), and improved weight-for-height (MD 0.20 z-score, 95% CI 0.03 to 0.37; 1546 children, two trials; moderate quality evidence). The reduction in mortality did not reach statistical significance (RR 0.44; 95% CI 0.14 to 1.36; 1974 children, one trial; low quality evidence). Lipid-based nutrient supplements versus any blended foods (dry food mixtures, without high lipid content), at full doses - there was no significant difference in mortality (RR 0.93, 95% CI 0.54 to 1.62; 6367 children, five trials; moderate quality evidence), progression to severe malnutrition (RR 0.88, 95% CI 0.72 to 1.07; 4537 children, three trials; high quality evidence), or the number of dropouts from the nutritional programme (RR 1.14, 95% CI 0.62 to 2.11; 5107 children, four trials; moderate quality evidence). However, lipid-based nutrient supplements significantly increased the number of children recovered (RR 1.10, 95% CI 1.04 to 1.16; 6367 children, five trials; moderate quality evidence), and decreased the number of non-recovering children (RR 0.53, 95% CI 0.40 to 0.69; 4537 children, three trials; high quality evidence). LNS also improved weight gain, weight-for-height, and mid-upper arm circumference, although for these outcomes, the improvement was modest (moderate quality evidence). One trial observed more children with vomiting in the lipid-based nutrient supplements group compared to those receiving blended food (RR 1.43, 95% CI 1.11 to 1.85; 2712 children, one trial; low quality evidence). Foods at complementary doses - no firm conclusion could be drawn on the comparisons between LNS at complementary dose and blended foods at complementary or full dose (low quality evidence). Lipid-based nutrient supplements versus specific types of blended foods - a recently developed enriched blended food (CSB++) resulted in similar outcomes to LNS (4758 children, three trials; moderate to high quality evidence). Different types of blended foods - in one trial, CSB++ did not show any significant benefit over locally made blended food, for example, Misola, in number who recovered, number who died, or weight gain (moderate to high quality evidence). Improved adequacy of home diet - no study evaluated the impact of improving adequacy of local diet, such as local foods prepared at home according to a given recipe or of home processing of local foods (soaking, germination, malting, fermentation) in order to increase their nutritional content. AUTHORS' CONCLUSIONS: In conclusion, there is moderate to high quality evidence that both lipid-based nutrient supplements and blended foods are effective in treating children with MAM. Although lipid-based nutrient supplements (LNS) led to a clinically significant benefit in the number of children recovered in comparison with blended foods, LNS did not reduce mortality, the risk of default or progression to SAM. It also induced more vomiting. Blended foods such as CSB++ may be equally effective and cheaper than LNS. Most of the research so far has focused on industrialised foods, and on short-term outcomes of MAM. There are no studies evaluating interventions to improve the quality of the home diet, an approach that should be evaluated in settings where food is available, and nutritional education and habits are the main determinants of malnutrition. There are no studies from Asia, where moderate acute malnutrition is most prevalent.

[Allergic enterocolitis with protein-losing enteropathy in a 5-month-old girl: a case report].

We report the case of a 5-month-old female infant who had allergic enterocolitis with protein-losing enteropathy and had low birth weight. Until the age of 4 months, she was fed only breast milk and did not experience any related problems. When she was 5-months-old, she was admitted to our hospital with the chief complaints of vomiting and diarrhea. She had whole body edema, thoracic and abdominal ascites, and bloody stools. Laboratory examinations showed the presence of hypoalbuminemia, hypogammaglobulinemia, and an elevated CRP level. Subsequently, she was fed an elemental diet with enteral tube feeding, and her condition gradually improved. However, 2 weeks later, her symptoms reappeared, and therefore, she was admitted to the National Center for Child Health and Development. She underwent upper and colon endoscopies and was found out to have multiple inflammatory lesions in the area extending from the cecum to the rectum. The biopsy findings showed features of eosinophilic enterocolitis and she was diagnosed with allergic eosinophilic enterocolitis. Subsequently, an elemental formula that does not include soybean was used for feeding the infant. The symptoms resolved and her condition improved; currently, she is well and is showing normal development. We have reported this case because allergic enterocolitis is becoming a topic of concern.