Evaluating the Pharmacoeconomic Impact of Nutrient Supplementation Post-operatively on Patients Receiving Roux-Y Gastric Bypass vs. Biliopancreatic Diversion with Duodenal Switch.

BACKGROUND: Without the needed medical support, bariatric surgery can be associated with post-operative malnutrition and associated nutrient deficiencies. We aimed to evaluate the cost difference of perioperative infusion requirements and TPN between GBP and BPD-DS. METHODS: All patients undergoing GBP or BPD-DS procedures between August 2015 and June 2018 were included. Information was collected to standardize the nutritional information into two categories: (1) oral supplementation and standard intravenous infusions, as predicted costs forming part of preoperative quote and (2) infusions prescribed for malnutrition, based on blood biochemistry, caterized as unexpected costs. RESULTS: A total of 573 patients over 3 years (GBP 60%, BPD-DS 40%) were included in the analysis. The average predicted costs from oral supplementation for both surgery groups and prophylactic infusions for BPD-DS were GBP (46.90USD) vs. BPD-DS (154.13 USD) (p-value = NS). Unexpected costs for infusions to correct nutritional deficiencies were GBP (199.14 USD) vs. BPD-DS (127.29 USD) (p-value = NS). TPN incidence rate was GBP (2.1%) and BPD-DS (12.7%) (p-value < 0.001) and admission rate per patient was GBP (0.9) and BPD-DS (0.63) (p-value < 0.05). Costs for acquiring TPN were GBP (153.58 USD) vs. BPD-DS (268.76 USD). Total unexpected costs were GBP (352.72 USD) vs. BPD-DS (396.05 USD) (p-value = NS). CONCLUSION: Nutrient deficiencies are known to occur within both GBP and BPD-DS surgeries, even up to 3 years. The admission rate/patient, requiring TPN, was higher in the GBP group, indicating that BPD-DS surgery can be efficient and cost-effective with holistic and multitherapeutic post-surgery care. BPD-DS procedures should be reserved for centers with a comprehensive and experienced multidisciplinary team enforcing stringent follow-up regimes.

An in vitro and in vivo study on the properties of hollow polycaprolactone cell-delivery particles.

The field of dermal fillers is evolving rapidly and numerous products are currently on the market. Biodegradable polymers such as polycaprolactone (PCL) have been found to be compatible with several body tissues, and this makes them an ideal material for dermal filling purposes. Hollow PCL spheres were developed by the Council for Scientific and Industrial Research (CSIR) to serve both as an anchor point and a "tissue harbour" for cells. Particles were tested for cytotoxicity and cell adherence using mouse embryo fibroblasts (MEF). MEFs adhered to the particles and no significant toxic effects were observed based on morphology, cell growth, cell viability and cell cycle analysis, suggesting that the particles are suitable candidates for cell delivery systems in an in vivo setting. The objective of providing a "tissue harbour" was however not realized, as cells did not preferentially migrate into the ported particles. In vivo studies were conducted in BALB/c mice into whom particles were introduced at the level of the hypodermis. Mice injected with PCL particles (ported and non-ported; with or without MEFs) showed evidence of local inflammation and increased adipogenesis at the site of injection, as well as a systemic inflammatory response. These effects were also observed in mice that received apparently inert (polystyrene) particles. Ported PCL particles can therefore act as a cell delivery system and through their ability to induce adipogenesis, may also serve as a dermal bulking agent.

Fibroblast-Derived Extracellular Matrix Induces Chondrogenic Differentiation in Human Adipose-Derived Mesenchymal Stromal/Stem Cells in Vitro.

Mesenchymal stromal/stem cells (MSCs) represent an area being intensively researched for tissue engineering and regenerative medicine applications. MSCs may provide the opportunity to treat diseases and injuries that currently have limited therapeutic options, as well as enhance present strategies for tissue repair. The cellular environment has a significant role in cellular development and differentiation through cell-matrix interactions. The aim of this study was to investigate the behavior of adipose-derived MSCs (ad-MSCs) in the context of a cell-derived matrix so as to model the in vivo physiological microenvironment. The fibroblast-derived extracellular matrix (fd-ECM) did not affect ad-MSC morphology, but reduced ad-MSC proliferation. Ad-MSCs cultured on fd-ECM displayed decreased expression of integrins α2 and ß1 and subsequently lost their multipotency over time, as shown by the decrease in CD44, Octamer-binding transcription factor 4 (OCT4), SOX2, and NANOG gene expression. The fd-ECM induced chondrogenic differentiation in ad-MSCs compared to control ad-MSCs. Loss of function studies, through the use of siRNA and a mutant Notch1 construct, revealed that ECM-mediated ad-MSCs chondrogenesis requires Notch1 and ß-catenin signaling. The fd-ECM also showed anti-senescence effects on ad-MSCs. The fd-ECM is a promising approach for inducing chondrogenesis in ad-MSCs and chondrogenic differentiated ad-MSCs could be used in stem cell therapy procedures.

Novel flow cytometric approach for the detection of adipocyte subpopulations during adipogenesis.

The ability of mesenchymal stromal cells (MSCs) to differentiate into adipocytes provides a cellular model of human origin to study adipogenesis in vitro. One of the major challenges in studying adipogenesis is the lack of tools to identify and monitor the differentiation of various subpopulations within the heterogeneous pool of MSCs. Cluster of differentiation (CD)36 plays an important role in the formation of intracellular lipid droplets, a key characteristic of adipocyte differentiation/maturation. The objective of this study was to develop a reproducible quantitative method to study adipocyte differentiation by comparing two lipophilic dyes [Nile Red (NR) and Bodipy 493/503] in combination with CD36 surface marker staining. We identified a subpopulation of adipose-derived stromal cells that express CD36 at intermediate/high levels and show that combining CD36 cell surface staining with neutral lipid-specific staining allows us to monitor differentiation of adipose-derived stromal cells that express CD36(intermediate/high)during adipocyte differentiation in vitro. The gradual increase of CD36(intermediate/high/)NR(positive)cells during the 21 day adipogenesis induction period correlated with upregulation of adipogenesis-associated gene expression.

Human adipose derived mesenchymal stromal cells transduced with GFP lentiviral vectors: assessment of immunophenotype and differentiation capacity in vitro.

Adipose derived mesenchymal stromal/stem cells (ASCs) are a heterogeneous population characterized by (a) their ability to adhere to plastic; (b) immunophenotypic expression of certain cell surface markers, while lacking others; and (c) the capacity to differentiate into lineages of mesodermal origin including osteocytes, chondrocytes and adipocytes. The long-term goal is to utilize these cells for clinical translation into cell-based therapies. However, preclinical safety and efficacy need to be demonstrated in animal models. ASCs can also be utilized as biological vehicles for vector-based gene delivery systems, since they are believed to home to sites of inflammation and infection in vivo. These factors motivated the development of a labelling system for ASCs using lentiviral vector-based green fluorescent protein (GFP) transduction. Human ASCs were transduced with GFP-expressing lentiviral vectors. A titration study determined the viral titer required to transduce the maximum number of ASCs. The effect of the transduced GFP lentiviral vector on ASC immunophenotypic expression of surface markers as well as their ability to differentiate into osteocytes and adipocytes were assessed in vitro. A transduction efficiency in ASC cultures of approximately 80 % was observed with an MOI of ~118. No significant immunophenotypic differences were observed between transduced and non-transduced cells and both cell types successfully differentiated into adipocytes and osteocytes in vitro. We obtained >80 % transduction of ASCs using GFP lentiviral vectors. Transduced ASCs maintained plastic adherence, demonstrated ASC immunophenotype and the ability to differentiate into cells of the mesodermal lineage. This GFP-ASC transduction technique offers a potential tracking system for future pre-clinical studies.