Biocell-Initial patents versus user instructions guide: A discrepancy at the core of a crisis.

PURPOSE: Our aim is to do a comparative qualitative analysis of patents and "User Manuals" of the Biocell textured implants in order to determine if red flags were omitted when marketing and using Biocell textured implants. MATERIALS AND METHODS: We performed a systematic qualitative analysis using the NVivo software version 11 of the patents describing the Biocell textured implants prior to their approval by the FDA and of user guides published by the 3 companies owning the patents (McGhan, Inamed, Allergan). To guide our thematic analysis, we used a form of systems theory known as the complexity theory. RESULTS: Four patents related to Biocell and 2 user manuals (McGhan- Inamed and Allergan) were analyzed. Four themes emerged from the patents: invention description, mechanism of action (Tissue ingrowth), the timing of the mechanism of action and hypothetical actions on capsular contractures prevention. Of all patent's content, 34% described the invention, 29% the mechanism of action (tissue ingrowth), 1% the timing of this mechanism of action and 34% a hypothetical action against capsular contracture. Solid evidence was found on the concept of anchoring and very little on capsular contracture. On the user guide side, the main themes were indications and contraindications, surgical techniques and long-term effects. The "directed" content analysis approach of the user guides regarding the patent's themes reflected that 94% of the user guides content related to the patent thematics was about the hypothetical role on capsular contracture while only 4% was about invention description and 1.5% about tissue ingrowth. CONCLUSIONS: This analysis highlights the discrepancies between patents of Biocell textured implants and user guides for these implants. The indications of use of a treatment or device can evolve quicker than the study of its potential complications and side effects. The BIA-ALCL crisis should serve as a cautionary tale to the plastic surgery community which embraces new technologies eagerly, and sometimes precariously, in a mission to advance patient care.

Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity.

BACKGROUND/OBJECTIVES: Cannabinoid receptor 1 (CB1) is the best-characterized cannabinoid receptor, and CB1 antagonists are used in clinical trials to treat obesity. Because of the wide range of CB1 functions, the side effects of CB1 antagonists pose serious concerns. G-protein-coupled receptor 55 (GPR55) is an atypical cannabinoid receptor, and its pharmacology and functions are distinct from CB1. GPR55 regulates neuropathic pain, gut, bone, immune functions and motor coordination. GPR55 is expressed in various brain regions and peripheral tissues. However, the roles of GPR55 in energy and glucose homeostasis are unknown. Here we have investigated the roles of GPR55 in energy balance and insulin sensitivity using GPR55-null mice (GPR55(-/-)). METHODS: Body composition of the mice was measured by EchoMRI. Food intake, feeding behavior, energy expenditure and physical activity of GPR55(-/-) mice were determined by indirect calorimetry. Muscle function was assessed by forced treadmill running test. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Adipose inflammation was assessed by flow cytometry analysis of adipose tissue macrophages. The expression of inflammatory markers in adipose tissues and orexigenic/anorexigenic peptides in the hypothalamus was also analyzed by real-time PCR. RESULTS: GPR55(-/-) mice had normal total energy intake and feeding pattern (i.e., no changes in meal size, meal number or feeding frequency). Intriguingly, whereas adult GPR55(-/-) mice only showed a modest increase in overall body weight, they exhibited significantly increased fat mass and insulin resistance. The spontaneous locomotor activity of GPR55(-/-) mice was dramatically decreased, whereas resting metabolic rate and non-shivering thermogenesis were unchanged. Moreover, GPR55(-/-) mice exhibited significantly decreased voluntary physical activity, showing reduced running distance on the running wheels, whereas muscle function appeared to be normal. CONCLUSIONS: GPR55 has an important role in energy homeostasis. GPR55 ablation increases adiposity and insulin resistance by selectively decreasing physical activity, but not by altering feeding behavior as CB1.

Insulin therapy for a non-diabetic patient with severe hypertriglyceridemia.

OBJECTIVE: To compare the short and long term effectiveness of fish oil, insulin, and gemfibrozil in a non-diabetic patient with severe hypertriglyceridemia. METHOD: An adolescent male with hypertriglyceridemia (triglyceride level 4575 mg/dl) and abdominal pain was treated with the goal of immediate reduction and maintenance of triglyceride (TG) level below 1000 mg/dl. Fish oil, insulin and gemfibrozil were administered sequentially, in separate time blocks, for a duration of 3, 6, and 6 months, respectively. RESULTS: Fish oil took several weeks to lower TG level, and patient compliance during 3 months of therapy was inadequate. Insulin was effective in immediately lowering the TG level, but was unable to maintain the level below 1000 mg/dl. Gemfibrozil was ineffective in achieving the immediate reduction of TG level; however, it was adequate in maintaining the desired level in the long-term and patient compliance was better than with the fish oil. CONCLUSION: In patients with risk of pancreatitis due to severe hypertriglyceridemia, immediate reduction of the triglyceride level is achievable by using a single dose of regular insulin (0.1 unit/kg, subcutaneous) while long-term maintenance therapy can be provided by gemfibrozil.