RESUMEN
During biomanufacturing, several unit operations expose solutions of biologics to multiple stresses, such as hydrodynamic shear forces due to fluid flow and interfacial dilatational stresses due to mechanical agitation or bubble collapse. When these stresses individually act on proteins adsorbed to interfaces, it results in an increase in protein particles in the bulk solution, a phenomenon referred to as interface-induced protein particle formation. However, an understanding of the dominant cause, when multiple stresses are acting simultaneously or sequentially, on interface-induced protein particle formation is limited. In this work, we established a unique set-up using a peristaltic pump and a Langmuir-Pockels trough to study the impact of hydrodynamic shear stress due to pumping and interfacial dilatational stress, on protein particle formation. Our experimental results together demonstrate that for protein solutions subjected to various combinations of stress (i.e., interfacial and hydrodynamic stress in different sequences), surface pressure values during adsorption and when subjected to compression/dilatational stresses, showed no change, suggesting that the interfacial properties of the protein film are not impacted by pumping. The concentration of protein particles is an order of magnitude higher when interfacial dilatational stress is applied at the air-liquid interface, compared to solutions that are only subjected to pumping. Furthermore, the order in which these stresses are applied, have a significant impact on the concentration of protein particles measured in the bulk solution. Together, these studies conclude that for biologics exposed to multiple stresses throughout bioprocessing and manufacturing, exposure to air-liquid interfacial dilatational stress is the predominant mechanism impacting protein particle formation at the interface and in the bulk solution.
RESUMEN
Background: Very low calorie diets (VLCDs) are an obesity treatment option in the general population, but their efficacy and safety in patients on haemodialysis (HD) is unknown. Methods: Prospective single arm study of VLCD in haemodialysis patients. All participants received 2.5-3.3 MJ/day for 12 weeks. Weekly assessment of VLCD, pre- and post-dialysis weight, inter-dialytic weight gain, and blood electrolytes occurred for the first 4 weeks, then fortnightly for another 8 weeks. Linear mixed models compared the change in weight over time as well as biochemical outcomes including potassium. Results: Twenty-two participants [nine home HD (HHD) and 13 satellite HD (SHD)] enrolled with 19 completing the 12-week intervention. Mean post-dialysis weight declined from 121.1 kg at baseline to 109.9 at week 12 resulting in average decline of 0.88 kg per week (95% C.I. 0.71, 1.05, P < .001) with 12-week mean percentage weight loss9.3% (SD 3.5). Mean post-dialysis body mass index declined from 40.9 kg/m2 at baseline to 37.1 kg/m2 at week 12 (95% C.I. 0.25, 0.35, P < .001). Serum potassium rose from week 1 to 3, stabilized during weeks 4 to 6, and fell from week 8, returning near baseline by week 12. Six of the nine (66.6%) HHD participants and seven of the 13 (70%) SHD participants had at least one episode of hyperkalaemia (K > 6 mmol/l). There were no clinical changes in serum sodium, corrected calcium, or phosphate levels during the study. Conclusion: VLCD with dietitian supervision was effective in producing significant weight reduction, with an acceptable safety profile in patients treated with haemodialysis.
RESUMEN
OBJECTIVE: Perform a comparison between the costs of image-guided breast procedures versus 2-year imaging follow-up for findings classified as BI-RADS assessment category 3-probably benign. METHODS: The national payment amount costs at non-facility locations were obtained from the Centers for Medicare and Medicaid Services physician fee schedule for breast imaging-related Current Procedural Terminology codes. Total costs were calculated and compared for management algorithms of 2-year imaging follow-up of a BI-RADS 3 lesion from 2018 through 2019 versus performing an image-guided procedure of the lesion in 2018 after the initial diagnostic imaging. RESULTS: Two-year mammographic follow-up of a BI-RADS 3 finding costs $484. This was less than a stereotactic-guided breast biopsy, which cost at least $1055. Two-year follow-up for a probably benign US finding cost $615 compared to $1173 for the least expensive US-guided breast biopsy scenario. For breast MRI, 2-year imaging follow-up cost $1510, which was also less than most MRI-guided breast biopsy scenarios. The one exception in which biopsy costs less than 2-year imaging follow-up was in the setting of an MRI-guided biopsy in the average-risk population without a post-benign biopsy follow-up breast MRI; in this setting, MRI biopsy cost $1235. CONCLUSION: In 2018-2019, 2-year imaging follow-up of a BI-RADS 3 finding continues to be less costly than an immediate procedure, except for MRI-guided breast biopsy in the average-risk population without a post-benign biopsy follow-up MRI.