The efficacy of vitamin E in preventing arthrofibrosis after joint replacement.

BACKGROUND: Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues. Vitamin E is an antioxidant with potential anti-fibroblastic effect. The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis. METHODS: We simulated knee replacement in 16 male Sprague-Dawley rats. We immobilized the surgical leg with a suture in full flexion. The control groups were killed at 2 and 12 weeks (n = 5 per group), and the test group was supplemented daily with vitamin E (0.2 mg/mL) in their drinking water for 12 weeks (n = 6). We performed histological staining to investigate the presence and severity of arthrofibrosis. Immunofluorescent staining and α2-macroglobulin (α2M) enzyme-linked immunosorbent assay (ELISA) were used to assess local and systemic inflammation. Static weight bearing (total internal reflection) and range of motion (ROM) were collected for functional assessment. RESULTS: The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups. Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue. Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels. The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group. CONCLUSIONS: This model is viable for simulating arthrofibrosis after joint replacement. Vitamin E may benefit postsurgical arthrofibrosis, and further studies are needed for dosing requirements.

A novel approach to characterize host cell proteins associated with therapeutic monoclonal antibodies.

Recombinant monoclonal antibody (mAb) products are widely produced in the pharmaceutical industry using Chinese hamster ovary (CHO) cells. Host cell proteins (HCPs) are one of many process-related impurities generated during the production of mAb products. The multi-analyte HCP enzyme linked immunosorbent assay (ELISA) is the industry standard accepted assay to measure clearance of HCPs from recombinant protein therapeutics. While similar platform processes are used for expression and purification, varying amounts of HCPs are found in final drug substances for different mAb products. Through the use of novel ELISA formats, an HCP-mAb product interaction was identified using a variety of ELISAs to investigate the underlying protein-protein interaction. This result provides evidence to explain why some mAb products have HCPs that are not cleared during purification. This ELISA technique can be used as a high-throughput screening tool to identify conditions to improve clearance of difficult HCPs during downstream processing purification. In addition, an interaction was observed to occur between anti-CHO HCP antibodies and mAb products. However, this interaction only occurs under denaturing conditions, and does not interfere with the HCP quantitation obtained by ELISA, and it was demonstrated that the cross-reactive anti-CHO HCP antibodies can be removed by affinity purification. Biotechnol. Bioeng. 2017;114: 1208-1214. © 2017 Wiley Periodicals, Inc.

Nutritional therapy in patients with acute pancreatitis requiring critical care unit management: a prospective observational study in Australia and New Zealand.

OBJECTIVE: To determine nutritional therapy practices of patients with severe acute pancreatitis (defined as those receiving critical care management in an intensive care unit or high-dependency unit) in Australia and New Zealand with focus on the choice of enteral nutrition or parenteral nutrition. DESIGN: Prospective observational multicentered study performed at 40 sites in Australia and New Zealand over 6 months. SETTING: Intensive care units or high-dependency units within Australia and New Zealand. PATIENTS: Those with severe acute pancreatitis diagnosed by elevated lipase and/or amylase. Patients with chronic pancreatitis were excluded. MEASUREMENTS: The primary outcome was the proportion of patients who received enteral nutrition, parenteral nutrition, or concurrent enteral nutrition/parenteral nutrition. Secondary outcomes included other aspects of nutritional therapy and the severity and clinical outcomes of acute pancreatitis. MEASUREMENTS AND MAIN RESULTS: We enrolled 121 patients and 117 were analyzed. The mean age was 61 (sd 17) years and 53% were men. Enteral nutrition was delivered to 58 (50%; 95% confidence interval [CI], 41-59%) and parenteral nutrition to 49 (42%; 95% CI, 33-51%) patients. Parenteral nutrition was more frequently used as the initial therapy (58%; 95% CI, 49-67%) than enteral nutrition (42%; 95% CI, 33-51%). The most common reason for parenteral nutrition prescription was the treating doctor's preference (60%). Enteral nutrition (74%) was more often used than parenteral nutrition (40%) on any individual study day. Concurrent enteral nutrition and parenteral nutrition occurred in 28 (24%) patients on 14% of days. Complications of acute pancreatitis requiring critical care unit management were observed in 45 (39%) patients. The median (interquartile range) duration of intensive care unit and hospital stay were 5 (2-10) and 19 (9-31) days, respectively. The hospital mortality rate was 15% (95% CI, 8-21%), and there was a tendency toward higher mortality for patients who only received parenteral nutrition than for those who only received enteral nutrition (28% vs. 7%, p=.06). CONCLUSIONS: For patients with acute pancreatitis requiring critical care unit management in Australian and New Zealand intensive care units, enteral nutrition is used most commonly, but parenteral nutrition is more often used as the initial route of nutritional therapy. Given that clinical practice guidelines currently recommend enteral nutrition as the initial route of nutritional therapy in severe acute pancreatitis, improved education about and dissemination of these guidelines seems warranted.

Nutritional support in acute pancreatitis.

PURPOSE OF REVIEW: This review explores the role of enteral and parenteral nutrition in severe acute pancreatitis and discusses the potential benefits of glutamine, omega-3 fatty acids, arginine and selenium together with probiotics and prebiotics in these patients. In addition, the method of refeeding during the convalescent period is also examined. RECENT FINDINGS: A complex picture is emerging in which enteral nutritional support may be important early in the course of the disease with parenteral nutrition being used more as a backup and possibly only after the systemic inflammatory response has peaked. Nasogastric feeding, sometimes supplemented by parenteral nutrition, is as efficacious as nasojejunal feeding. An individualized approach, in which strategies of nutritional support are tailored to patient response, is gaining currency. Data regarding specialized formulae are mixed but the use of prebiotics is showing promise and is worthy of further exploration. In the convalescent period, preliminary data also indicate that the risk of pain developing is no greater if a light diet is instituted rather than clear fluids. SUMMARY: Nutritional support in acute pancreatitis remains challenging and controversial with a number of different and unexpected approaches, including the use of nasogastric feeding and dual enteral and parenteral nutrition support, being adopted in recent clinical trials.