Protein trans-splicing by the naturally split intein of the gene dnaE from Nostoc punctiforme (Npu DnaE) was demonstrated here with non-native exteins in Escherichia coli. Npu DnaE possesses robust trans-splicing activity with an efficiency of >98%, which is superior to that of the DnaE intein from Synechocystis sp. strain PCC6803 (Ssp DnaE). Both the N-and C-terminal parts of the split Npu DnaE intein can be substituted with the corresponding fragment of Ssp DnaE without loss of trans-splicing activity. Protein splicing with the Npu DnaE N is also more tolerant of amino acid substitutions in the C-terminal extein sequence.
The purpose of this overview is to make the case for the establishment and publication of standards for home enteral nutrition (HEN) therapy in adult patients who require a long-term alternative to oral feeding. Overviews can provide a broad and often comprehensive summation of a topic area and, as such, have value for those coming to a subject for the first time. It will provide a broad summation, background and rationale, review specific considerations unique to HEN (tubes, products and supplies) and we describe a recent audit of seven HEN programs which highlights tube and process related challenges. Based on the overview of the literature and our experience with the audit we propose a way forward for best home enteral nutrition care.
Trace elements (TEs) are an essential component of parenteral nutrition (PN). Over the last few decades, there has been increased experience with PN, and with this knowledge more information about the management of trace elements has become available. There is increasing awareness of the effects of deficiencies and toxicities of certain trace elements. Despite this heightened awareness, much is still unknown in terms of trace element monitoring, the accuracy of different assays, and current TE contamination of solutions. The supplementation of TEs is a complex and important part of the PN prescription. Understanding the role of different disease states and the need for reduced or increased doses is essential. Given the heterogeneity of the PN patients, supplementation should be individualized.
Removal of Mn as an additive in HPN solutions resulted in resolution of MRI abnormalities in most patients. Over 5 years, all patients except for 1 maintained normal blood Mn levels. Therefore, Mn levels should be monitored and supplementation be individualized.
A 57-year-old woman, with colonic Crohn disease (CD) diagnosed four years previously, presented to the emergency department with a six-week history of severe abdominal pain. She did not have diarrhea. She had inactive perianal fistulas. Laboratory tests at presentation showed an elevated C-reactive protein level of 103 mg/L, and low albumin of 24 g/L. Other bloodwork was unremarkable. Stool testing was negative for Clostridium difficile, and culture and sensitivity. Her medical history was significant for rheumatoid arthritis (RA). She had been receiving infliximab and methotrexate for RA and CD. A computed tomography scan revealed wall thickening in the ascending, transverse and descending colon. No lymphadenopathy was present. Pericolonic inflammatory changes were apparent. No obstruction was present. Colonoscopy at the time of admission, to confirm what appeared to be a CD flare, revealed a benign-appearing ulcerated stricture at 40 cm from the anal verge (Figure 1). The colonoscope could not pass the stricture. There was no active CD in the colon distal to the stricture. The stricture was biopsied. The patient was treated with intravenous solumedrol and, subsequently, prednisone for a presumed CD flare. Steroids led to resolution of her pain. Biopsies of the stricture unexpectedly revealed an anaplastic large cell lymphoma (ALCL) (Figure 2). Infliximab and methotrexate were discontinued. A bone marrow biopsy was negative for lymphoma and computed tomography enterography showed a normal small bowel. The patient successfully completed six cycles of CHOP (cyclophosphamide, hydroxy doxorubicin, vincristine, prednisone) chemotherapy. Repeat biopsies of the stricture postchemotherapy showed no lymphoma, but atypical cells were present (Figure 3). A tattoo was used to mark the location of the stricture. The stricture was balloon-dilated to allow visualization of the proximal colon. There was only a single, discrete patch of ulceration in the ascending colon. Biopsies here were consistent with CD. It was believed that her risk of lymphoma recurrence was high. She was referred for surgical intervention and underwent a left hemicolectomy.
Background Malnutrition is common in hospitalized patients and strategies to improve energy and protein intake have a positive impact on outcome. Despite early evidence suggesting the usefulness of peripheral parenteral nutrition (PPN), its adoption has been hampered by concerns regarding safety and efficacy. This study addresses this issue. Methods This prospective observational study was performed in medical and surgical inpatients in who were screened for nutrition risk and assessed using Subjective Global Assessment (SGA). Data captured included nutrition status, energy and protein requirements, intravenous access, indications for PPN, use of supplemental micronutrients, and disposition of patients on PPN. Results Ninety‐eight patients were recruited from two centers over 8 months. The average age was 61.5 years, the mean Charlson Comorbidity Index was 4.21 (±3.09), 52% were male, and 48% were admitted to medicine, whereas 52% were admitted to surgery. Thirty‐three percent of patients were SGA C, 44% were SGA B, and 19% were SGA A. Twenty‐seven percent of patients had cancer. The average length of hospital stay was 22 days. The main indications for PPN were gastrointestinal tract dysfunction (72%) and postsurgical status (16%). PPN provided an average of 1296 kcal (±191) and 46 g of protein (±7). Intravenous access complications in patients receiving PPN did not occur in excess of expected. Almost 40% of patients required transition to central PN. Conclusions PPN is a safe, effective way to deliver supplemental protein, energy, and micronutrients to malnourished patients and supports transition to other modes of nutrition care.
Background Home parenteral nutrition (HPN) can be associated with increased liver enzymes, catheter-related bloodstream infections (CRBSI), and hospitalizations. Mixed oil (MO) versus soybean oil (SO) lipid emulsion reduces risks in hospitalized patients, but there are no randomized double-blinded controlled trials in HPN. Therefore, the primary objective was to test the study’s feasibility such as recruitment and retention in the HPN population and the secondary objective was to assess changes in liver enzymes between MO and SO as well as other clinical and biochemical outcomes. Methods This 13-month prospective double-blind crossover randomized pilot trial took place in Toronto, Canada. Participants were HPN patients who were a part of the HPN program at Toronto General Hospital. We recruited patients from the HPN program. HPN patients receiving SO were randomized to either MO or SO, and the study duration was 6 months in each arm (MO or SO) with a 1-month washout period resuming SO. As this is a crossover trial design, the patient is his/her own control. The main outcome measures were descriptions of study feasibility, namely the study recruitment and retention. We also collected biochemical parameters, CRSBI, hospitalization rate, antibiotic use, and mortality. Demographic, nutritional, clinical, and laboratory data were collected at baseline, 3 and 6 months of each arm. The primary analysis population was defined as the per-protocol population who completed the trial including all lipid measurements. Results A total of 65 HPN patients were assessed, and 60 met the inclusion criteria for the study. Thirty-five percent (21/60) were randomized using a computer-generated random number sequence generator: 10 participants were randomized to receive SO first while 11 were randomized to receive MO first. At 13 months, 3/10 who received SO first completed the study, whereas 9/11 who received MO first completed the study. This did not meet our a priori criteria for success in recruitment and retention. Between types of lipid emulsions, there were no significant differences in changes in liver enzymes or biochemical and clinical outcomes, despite significant changes in plasma free fatty acid composition reflecting MO or SO. Conclusions Overall, this pilot trial demonstrated that the use of a prospective double-blind, crossover, randomized trial design was not feasible to conduct in the HPN population because of difficulties in recruiting and retaining patients. In addition, there was no significant impact of MO versus SO lipid emulsion on liver enzymes or most parameters. The lack of significance may be attributed to low sample size from low recruitment and high drop-out rate, short study duration (6 months/arm), and complex care. In a future definitive trial, a multicenter study of longer duration and a larger sample size is recommended, and drop-outs may be reduced by using a parallel study design. Trial registration ClinicalTrials.gov, NCT02796833. Registered on 13 June 2016—retrospectively registered.
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