Lipid emulsions – Guidelines on Parenteral Nutrition, Chapter 6

The infusion of lipid emulsions allows a high energy supply, facilitates the prevention of high glucose infusion rates and is indispensable for the supply with essential fatty acids. The administration of lipid emulsions is recommended within ≤7 days after starting PN (parenteral nutrition) to avoid deficiency of essential fatty acids. Low-fat PN with a high glucose intake increases the risk of hyperglycaemia. In parenterally fed patients with a tendency to hyperglycaemia, an increase in the lipid-glucose ratio should be considered. In critically ill patients the glucose infusion should not exceed 50% of energy intake. The use of lipid emulsions with a low phospholipid/triglyceride ratio is recommended and should be provided with the usual PN to prevent depletion of essential fatty acids, lower the risk of hyperglycaemia, and prevent hepatic steatosis. Biologically active vitamin E (α-tocopherol) should continuously be administered along with lipid emulsions to reduce lipid peroxidation. Parenteral lipids should provide about 25–40% of the parenteral non-protein energy supply. In certain situations (i.e. critically ill, respiratory insufficiency) a lipid intake of up to 50 or 60% of non-protein energy may be reasonable. The recommended daily dose for parenteral lipids in adults is 0.7–1.3 g triglycerides/kg body weight. Serum triglyceride concentrations should be monitored regularly with dosage reduction at levels >400 mg/dl (>4.6 mmol/l) and interruption of lipid infusion at levels >1000 mg/dl (>11.4 mmol/l). There is little evidence at this time that the choice of different available lipid emulsions affects clinical endpoints

Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with the ceramide analogue LCL29. Evidence from mouse squamous cell carcinomas

Photodynamic therapy (PDT) has been proven effective for treatment of several types of cancer. Photodynamic therapy alone, however, attains limited cures with some tumours and there is need for its improved efficacy in such cases. Sphingolipid (SL) analogues can promote tumour response in combination with anticancer drugs. In this study, we used mouse SCCVII squamous cell carcinoma tumours to determine the impact of Photofrin-PDT on the in vivo SL profile and the effect of LCL29, a C6-pyridinium ceramide, on PDT tumour response. Following PDT, the levels of dihydroceramides (DHceramides), in particular C20-DHceramide, were elevated in tumours. Similarly, increases in DHceramides, in addition to C20:1-ceramide, were found in PDT-treated SCCVII cells. These findings indicate the importance of the de novo ceramide pathway in Photofrin-PDT response not only in cells but also in vivo. Notably, co-exposure of SCCVII tumours to Photofrin-PDT and LCL29 led to enhanced tumour response compared with PDT alone. Thus, we show for the first time that Photofrin-PDT has a distinct signature effect on the SL profile in vitro and in vivo, and that the combined treatment advances PDT therapeutic gain, implying translational significance of the combination

The action of a multidisciplinary team in the nutritional care of critically ill patients

Hospitalized patients may have special nutrient requirements imposed by a combination of malnutrition and enhanced utilization of nutrients resulting from the disease process. Nutritional support, mainly during critical stages of disease, should be provided safely and effectively. Several studies have evaluated the paper of a multidisciplinary team in the administration of a nutritional therapy. Individually, the majority of these studies are underpowered to evaluate an effect on the quality of nutritional care. With the objective to identify problems inherent to the supply of nutritional support to hospitalized patients and verify the impact of the actions of a multidisciplinary team on the quality of these procedures, we analysed articles that have been published between 1980 and 2004 about the role of the action of multidisciplinary teams in the care and nutritional outcome of hospitalized patients, especially those undergoing intensive care. The terms used for the search were: multidisciplinary team, nutritional support, parenteral nutrition, enteral feeding, critically ill, intensive care unit, critically ill child. Of 130 studies, intially identified, just 24 were selected, of which 14 compared the standard of nutritional therapy with and without the presence of a multidisciplinary team. The inadequate supply of nutrients, infection and metabolic complications and the excessive use of parenteral nutrition were the main problems detected in the supply of nutritional support to hospitalized patients. In the comparative studies, the presence of the multidisciplinary team improved the pattern of nutritional support, and reduced the incidence of complications and the costs.Pacientes hospitalizados podem ter necessidades nutricionais especiais em função da desnutrição e dos desequilíbrios metabólicos impostos pelas doenças. A terapia nutricional, principalmente nos estágios críticos das enfermidades, deve ser administrada de modo seguro e eficaz. Vários estudos têm avaliado o papel da equipe multidisciplinar na administração da terapia nutricional. Com o objetivo de identificar os problemas inerentes à administração da terapia nutricional em pacientes hospitalizados e verificar o impacto da atuação de uma equipe multidisciplinar na qualidade dos procedimentos, foi realizada uma revisão que analisou artigos publicados entre 1980 e 2004 sobre o papel da atuação de equipes multidisciplinares no cuidado e na evolução nutricional de pacientes hospitalizados, principalmente os que se encontravam sob cuidados intensivos. Os termos utilizados na pesquisa foram: multidisciplinary team, nutritional support, parente-ral nutrition, enteral feeding, critically ill, intensive care unit,critically ill child. Dos 130 estudos inicialmente identificados, foram selecionados 24, dos quais 14 compararam o padrão de terapia nutricional com e sem a presença da equipe multidisciplinar. Os principais problemas detectados na administração de terapia nutricional em pacientes hospitalizados foram a oferta inadequada de nutrientes, as complicações infecciosas e metabólicas e o uso excessivo de nutrição parenteral. Nos estudos comparativos, a presença da equipe multidisciplinar melhorou o padrão de oferta nutricional, reduziu a incidência de complicações e os custos.Universidade Federal de São Paulo (UNIFESP) Departamento de PediatriaHospital São Paulo Unidade de Cuidados Intensivos PediátricosHospital São Paulo Equipe Multidisciplinar de Terapia NutricionalUNIFESP, Depto. de PediatriaHospital São Paulo Unidade de Cuidados Intensivos PediátricosHospital São Paulo Equipe Multidisciplinar de Terapia NutricionalSciEL

A data-driven synthesis of research evidence for domains of hearing loss, as reported by adults with hearing loss and their communication partners

A number of assessment tools exist to evaluate the impact of hearing loss, with little consensus among researchers as to either preference or psychometric adequacy. The item content of hearing loss assessment tools should seek to capture the impact of hearing loss on everyday life, but to date no one has synthesized the range of hearing loss complaints from the perspectives of the person with hearing loss and their communication partner. The current review aims to synthesize the evidence on person with hearing loss- and communication partner-reported complaints of hearing loss. Searches were conducted in Cos Conference Papers Index, the Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, PubMed, Web of Science, and Google Scholar to identify publications from May 1982 to August 2015. A manual search of four relevant journals updated the search to May 2017. Of the 9,516 titles identified, 78 records (comprising 20,306 participants) met inclusion criteria and were taken through to data collection. Data were analyzed using meta-ethnography to form domains representing the person with hearing loss- and communication partner-reported complaints of hearing loss as reported in research. Domains and subdomains mutual to both perspectives are related to ‘‘Auditory’’ (listening, communicating, and speaking), ‘‘Social’’ (relationships, isolation, social life, occupational, and interventions), and ‘‘Self’’ (effort and fatigue, emotions, identity, and stigma). Our framework contributes fundamental new knowledge and a unique resource that enables researchers and clinicians to consider the broader impacts of hearing loss. Our findings can also be used to guide questions during diagnostic assessment and to evaluate existing measures of hearing loss

Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice

The sphingolipid ceramide is intimately involved in the growth, differentiation, senescence, and death of normal and cancerous cells. Mitochondria are increasingly appreciated to play a key role in ceramide-induced cell death. Recent work showed the C16-pyridinium ceramide analogue LCL-30 to induce cell death in vitro by mitochondrial targeting. The aim of the current study was to translate these results to an in vivo model. We found that LCL-30 accumulated in mitochondria in the murine colorectal cancer cell line CT-26 and reduced cellular ATP content, leading to dose- and time-dependent cytotoxicity. Although the mitochondrial levels of sphingosine-1-phosphate (S1P) became elevated, transcription levels of ceramide-metabolising enzymes were not affected. In mice, LCL-30 was rapidly absorbed from the peritoneal cavity and cleared from the circulation within 24 h, but local peritoneal toxicity was dose-limiting. In a model of subcutaneous tumour inoculation, LCL-30 significantly reduced the proliferative activity and the growth rate of established tumours. Sphingolipid profiles in tumour tissue also showed increased levels of S1P. In summary, we present the first in vivo application of a long-chain pyridinium ceramide for the treatment of experimental metastatic colorectal cancer, together with its pharmacokinetic parameters. LCL-30 was an efficacious and safe agent. Future studies should identify an improved application route and effective partners for combination treatment

A New Mixed-Backbone Oligonucleotide against Glucosylceramide Synthase Sensitizes Multidrug-Resistant Tumors to Apoptosis

Enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) limits therapeutic efficiencies of antineoplastic agents including doxorubicin in drug-resistant cancer cells. Aimed to determine the role of GCS in tumor response to chemotherapy, a new mixed-backbone oligonucleotide (MBO-asGCS) with higher stability and efficiency has been generated to silence human GCS gene. MBO-asGCS was taken up efficiently in both drug-sensitive and drug-resistant cells, but it selectively suppressed GCS overexpression, and sensitized drug-resistant cells. MBO-asGCS increased doxorubicin sensitivity by 83-fold in human NCI/ADR-RES, and 43-fold in murine EMT6/AR1 breast cancer cells, respectively. In tumor-bearing mice, MBO-asGCS treatment dramatically inhibited the growth of multidrug-resistant NCI/ADR-RE tumors, decreasing tumor volume to 37%, as compared with scrambled control. Furthermore, MBO-asGCS sensitized multidrug-resistant tumors to chemotherapy, increasing doxorubicin efficiency greater than 2-fold. The sensitization effects of MBO-asGCS relied on the decreases of gene expression and enzyme activity of GCS, and on the increases of C18-ceramide and of caspase-executed apoptosis. MBO-asGCS was accumulation in tumor xenografts was greater in other tissues, excepting liver and kidneys; but MBO-asGCS did not exert significant toxic effects on liver and kidneys. This study, for the first time in vivo, has demonstrated that GCS is a promising therapeutic target for cancer drug resistance, and MBO-asGCS has the potential to be developed as an antineoplastic agent

Is complementary and alternative medicine (CAM) cost-effective? a systematic review

BACKGROUND: Out-of-pocket expenditures of over $34 billion per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine (CAM) therapies have benefits that outweigh their costs. However, regardless of public opinion, there is often little more than anecdotal evidence on the health and economic implications of CAM therapies. The objectives of this study are to present an overview of economic evaluation and to expand upon a previous review to examine the current scope and quality of CAM economic evaluations. METHODS: The data sources used were Medline, AMED, Alt-HealthWatch, and the Complementary and Alternative Medicine Citation Index; January 1999 to October 2004. Papers that reported original data on specific CAM therapies from any form of standard economic analysis were included. Full economic evaluations were subjected to two types of quality review. The first was a 35-item checklist for reporting quality, and the second was a set of four criteria for study quality (randomization, prospective collection of economic data, comparison to usual care, and no blinding). RESULTS: A total of 56 economic evaluations (39 full evaluations) of CAM were found covering a range of therapies applied to a variety of conditions. The reporting quality of the full evaluations was poor for certain items, but was comparable to the quality found by systematic reviews of economic evaluations in conventional medicine. Regarding study quality, 14 (36%) studies were found to meet all four criteria. These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions: acupuncture for migraine, manual therapy for neck pain, spa therapy for Parkinson's, self-administered stress management for cancer patients undergoing chemotherapy, pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery, biofeedback for patients with "functional" disorders (eg, irritable bowel syndrome), and guided imagery, relaxation therapy, and potassium-rich diet for cardiac patients. CONCLUSION: Whereas the number and quality of economic evaluations of CAM have increased in recent years and more CAM therapies have been shown to be of good value, the majority of CAM therapies still remain to be evaluated