Pre-procedural serum albumin concentration is associated with length of stay, discharge destination, and 90-day mortality in patients after transcatheter aortic valve replacement.

Background: As visceral protein expression may influence outcomes in patients with cardiovascular disease, we investigated whether pre-procedural albumin concentration is associated with length of stay (LOS) and 90-day mortality after transcatheter aortic valve repair (TAVR). Methods: We retrospectively analyzed data from TAVR patients at our institution between January 2013 and December 2017. For all patients, baseline albumin concentration was assessed between one and four weeks before the procedure. To investigate the association between albumin concentration and outcomes, we performed regression analyses, controlling for Society of Thoracic Surgeons, New York Heart Association classification, and Kansas City Cardiomyopathy Questionnaire 12 scores. Results: Three hundred eighty patients were included in the analyses. Cox-proportional hazards regression showed that patients with albumin concentrations <3.5 g/dL were 80% more likely to have prolonged ICU LOS (HR 1.79; 95%CI 1.04-2.57, P = 0.03) and 70% more likely to have prolonged hospital LOS (HR 1.68; 95%CI 1.01-2.46, P = 0.04) compared to patients with albumin concentrations >3.5 g/dL. Logistic regression showed that patients with albumin concentrations <3.5 g/dL were four times more likely to not survive to 90 days (OR 3.94; 1.13-12.63, P = 0.03) after their TAVR compared to patients with albumin concentrations >3.5 g/dL. Conclusion: Our data suggest that patients with pre-procedural albumin concentrations <3.5 g/dL are at an increased risk of adverse outcomes after TAVR compared to patients with albumin concentrations ≥3.5 g/dL. Prospective studies are needed to determine whether risk stratification based on pre-procedural albumin can improve outcomes and whether targeted interventions can improve pre-procedural albumin concentrations in potential TAVR candidates.

Functional Outcomes of 24-Hour Thumb Immobilization in Healthy Volunteers: Prospective Comparative Study.

Background Immobilization is often needed for the treatment of wrist and hand injuries. The current best method of immobilization for several types of injuries has yet to be elucidated with little being reported on the functional differences of each type of immobilization. Purpose The purpose of this study is to compare the functional outcome between healthy young volunteers with a 24-hour short arm cast (SAC) versus thumb spica cast (TSC) immobilization. Methods A total of 50 healthy volunteers completed a baseline typing assessment and a Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity functional scoring assessment. Participants in group 1 were randomly initially assigned to a TSC of their dominant hand followed by an SAC, whereas participants in group 2 were randomly initially assigned to a TSC of their nondominant hand followed by an SAC. The volunteers completed the typing assessment and PROMIS assessment at the end of the 24-hour casting period. Results A total of 50 participants were enrolled in the study with 25 in group 1 and 25 in group 2. There was a 24.3-point difference between the average PROMIS score for participants with SAC compared with participants with TSC (93 vs. 68.7; p = 0.0001). There was a significant difference between the typing speed and accuracy of participants with SAC compared with participants with TSC ( p = 0.0001). Conclusion There is a significant difference in functionality of a TSC immobilization versus an SAC immobilization according to the PROMIS functional outcome score and typing speed in a 24-hour casting period. SAC immobilization should be considered to have a possible similar effect in pathologic conditions instead of TSC immobilization given these findings even though a 24-hour period is not enough to provide adequate long-term conclusions. Level of Evidence I, prospective comparative study.

Bone morphogenetic protein-2-mediated pain and inflammation in a rat model of posterolateral arthrodesis.

BACKGROUND: Bone morphogenetic protein-2 (BMP-2) is a pleiotropic, secreted molecule with diverse effects. The potent ability of BMP-2 to stimulate bone growth prompted its widespread clinical use for arthrodesis (spine fusion). However, elevated post-operative pain in patients treated with BMP-2 has been increasingly reported. Determining whether BMP-2 induces pain directly or whether it induces neuroinflammation, which could lower the threshold for pain, is important for developing therapeutic interventions. We therefore modeled the clinical use of BMP-2 for posterior lumbar fusion by implanting absorbable collagen sponges soaked with either recombinant human BMP-2 (rhBMP-2) or vehicle above the L4-L5 transverse processes of rat spine. RESULTS: Using microarray analysis we found that implantation of rhBMP-2-soaked absorbable collagen sponges resulted in altered expression of numerous pro-inflammatory genes in the adjacent dorsal root ganglia (DRG) showing that implantation of rhBMP-2/absorbable collagen sponges triggers potent neuroinflammatory responses in the DRG-2. Interestingly, direct BMP-2 treatment of DRG explants resulted in changes in gene expression that were not specifically pro-inflammatory. Rats implanted with rhBMP-2 in absorbable collagen sponges also exhibited a transient change in thermal and mechanical sensitivity indicating that rhBMP-2 applied to the lumbar spine could increase pain sensitivity. Immunohistochemical analysis indicated macrophage infiltration in the DRG and spinal nerve in rats implanted with rhBMP-2/absorbable collagen sponges or absorbable collagen sponges alone, but not in rats that underwent surgery without implantation of the absorbable collagen sponges suggesting that the sponges contributed to the biological response. Indeed, analysis of DRGs taken from rats implanted with absorbable collagen sponges without rhBMP-2 showed a significant change in gene expression distinct from DRGs from rats undergoing surgery only. CONCLUSIONS: Our data indicate that implantation of rhBMP-2/absorbable collagen sponges on the lumbar spine triggers potent neuroinflammatory responses in the DRG. Importantly, however, these BMP-2 effects may be partially mediated through a response to the absorbable collagen sponges.

Mammalian gastrointestinal tract parameters modulating the integrity, surface properties, and absorption of food-relevant nanomaterials.

Many natural chemicals in food are in the nanometer size range, and the selective uptake of nutrients with nanoscale dimensions by the gastrointestinal (GI) tract is a normal physiological process. Novel engineered nanomaterials (NMs) can bring various benefits to food, e.g., enhancing nutrition. Assessing potential risks requires an understanding of the stability of these entities in the GI lumen, and an understanding of whether or not they can be absorbed and thus become systemically available. Data are emerging on the mammalian in vivo absorption of engineered NMs composed of chemicals with a range of properties, including metal, mineral, biochemical macromolecules, and lipid-based entities. In vitro and in silico fluid incubation data has also provided some evidence of changes in particle stability, aggregation, and surface properties following interaction with luminal factors present in the GI tract. The variables include physical forces, osmotic concentration, pH, digestive enzymes, other food, and endogenous biochemicals, and commensal microbes. Further research is required to fill remaining data gaps on the effects of these parameters on NM integrity, physicochemical properties, and GI absorption. Knowledge of the most influential luminal parameters will be essential when developing models of the GI tract to quantify the percent absorption of food-relevant engineered NMs for risk assessment.

LPS antagonism of TGF-ß signaling results in prolonged survival and activation of rat primary microglia.

Accumulating evidence indicates that activated microglia contribute to the neuropathology involved in many neurodegenerative diseases and after traumatic injury to the CNS. The cytokine transforming growth factor-beta 1 (TGF-ß1), a potent deactivator of microglia, should have the potential to reduce microglial-mediated neurodegeneration. It is therefore perplexing that high levels of TGF-ß1 are found in conditions where microglia are chronically activated. We hypothesized that TGF-ß1 signaling is suppressed in activated microglia. We therefore activated primary rat microglia with lipopolysaccharide (LPS) and determined the expression of proteins important to TGF-ß1 signaling. We found that LPS treatment decreased the expression of the TGF-ß receptors, TßR1 and TßR2, and reduced protein levels of Smad2, a key mediator of TGF-ß signaling. LPS treatment also antagonized the ability of TGF-ß to suppress expression of pro-inflammatory cytokines and to induce microglial cell death. LPS treatment similarly inhibited the ability of the TGF-ß related cytokine, Activin-A, to down-regulate expression of pro-inflammatory cytokines and to induce microglial cell death. Together, these data suggest that microglial activators may oppose the actions of TGF-ß1, ensuring continued microglial activation and survival that eventually may contribute to the neurodegeneration prevalent in chronic neuroinflammatory conditions.

Engineered Nanoscale Food Ingredients: Evaluation of Current Knowledge on Material Characteristics Relevant to Uptake from the Gastrointestinal Tract.

The NanoRelease Food Additive project developed a catalog to identify potential engineered nanomaterials (ENMs) used as ingredients, using various food-related databases. To avoid ongoing debate on defining the term nanomaterial, NanoRelease did not use any specific definition other than the ingredient is not naturally part of the food chain, and its dimensions are measured in the nanoscale. Potential nanomaterials were categorized based on physical similarity; analysis indicated that the range of ENMs declared as being in the food chain was limited. Much of the catalog's information was obtained from product labeling, likely resulting in both underreporting (inconsistent or absent requirements for labeling) and/or overreporting (inability to validate entries, or the term nano was used, although no ENM material was present). Three categories of ingredients were identified: emulsions, dispersions, and their water-soluble powdered preparations (including lipid-based structures); solid encapsulates (solid structures containing an active material); and metallic or other inorganic particles. Although much is known regarding the physical/chemical properties for these ingredient categories, it is critical to understand whether these properties undergo changes following their interaction with food matrices during preparation and storage. It is also important to determine whether free ENMs are likely to be present within the gastrointestinal tract and whether uptake of ENMs may occur in their nanoform physical state. A practical decision-making scheme was developed to help manage testing requirements.

Measurement Methods for the Oral Uptake of Engineered Nanomaterials from Human Dietary Sources: Summary and Outlook.

This article is one of a series of 4 that report on a task of the NanoRelease Food Additive (NRFA) project of the International. Life Science Institute Center for Risk Science Innovation and Application. The project aims are to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article offers an overview of the NRFA project, describing the project scope and goals, as well as the strategy by which the task group sought to achieve these goals. A condensed description of the general challenge of detecting ENMs in foods and a brief review of available and emerging methods for ENM detection is provided here, paying particular attention to the kind of information that might be desired from an analysis and the strengths and weaknesses of the various approaches that might be used to attain this information. The article concludes with an executive summary of the task group's broad findings related to the 3 topic areas, which are covered in more detail in 3 subsequent articles in this series. The end result is a thorough evaluation of the state of ENM measurement science specifically as it applies to oral uptake of ENMs from human dietary sources.