Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study):study protocol for a randomized, controlled, multicenter, international clinical trial

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Disseminação linfática na endometriose colorretal

A 40-year-old female patient presented abdominal pain during her periods and progressing constipation during the last 6 years. Retosigmoidoscopy showed a stenotic lesion 14cm above the anal verge. The patient underwent a retosigmoidectomy and the specimen was sent to histopathologic exam. The diagnose was endometriosis with the involvement of the colon and rectum, associated with dissemination of the endometrial cells by the lymph nodes. The patient recovered well and was discharged on the 6th postoperative day. It is commented on the rarity of the lymphatic dissemination in these cases and according to the reviewed literature, this is the 5th case reported. Thus, dissemination of the disease to extra-abdominal sites could possibly occur by this route. Therefore, pathologists should carefully exam the lymph nodes of the mesocolon in these specimens because findings of endometrial "metastasis" may be present

Needs Assessment for Weight Management: The Learning Health System Network Experience

Objective: To assess patients’ weight management needs and experiences across multiple sites within the Learning Health System Network. Patients and Methods: A total of 19,964 surveys were sent to patients identified with overweight or obesity through medical record query at 5 health care systems throughout 11 states. The survey collected patients’ experiences with and opinions about weight management in clinical care from October 27, 2017, through March 1, 2018. Results: Among the 2380 responders, being younger, female, nonwhite, and single and having some college education or less were all significantly associated with higher body mass index (BMI). The most frequent weight loss barriers included food cravings (30.7%-49.9%) and having a medical condition limiting physical activity (17.7%-47.1%) (P<.001). Higher BMI was associated with a higher frequency of comorbidities and lower health status (P<.001). Higher BMI was also associated with a higher belief that primary care providers (PCPs) should be involved in weight loss management (P=.01) but lower belief that the PCP had the necessary skills and knowledge to help (P<.001). Responders with a higher BMI were more likely to feel judged (P<.001) and not always respected (P<.001) by their PCP. In addition, those with a higher BMI more frequently reported avoiding health care visits because of weight gain, not wanting to undress or be weighed, and not wanting to discuss their weight with their PCP (P<.001). Conclusion: Physician involvement in weight management is important to patients whose needs and experiences differ by BMI. These data may inform clinical weight management efforts and create greater alignment with patient expectations