Early Diet Liberalization After Anterior Lumbar Interbody Fusion Improves Postoperative Recovery.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: The objective of this study was to assess the impact of diet liberalization on short-term outcomes in patients undergoing anterior interbody lumbar fusion (ALIF). METHODS: A retrospective review was performed for patients undergoing ALIF at our tertiary care center institution from 2010 to 2022. Electronic medical records were reviewed for demographics, surgical characteristics, and 90-day postoperative outcomes. RESULTS: We included 515 patients in this study with 102 patients receiving a full diet on the same day as their operation. All other patients had a delay of at least 1 day (average 1.6 days) until a full diet was provided. This group was found to have a higher rate of postoperative ileus (10.2% vs 2.9%) and urinary retention (16.0% vs 3.9%). The readmission rate and percent of patients presenting to the emergency department within 90 days postoperatively were similar. On multivariate regression analysis, same-day, full-diet patients had decreased odds of developing urinary retention (OR = .17) and a shorter length of hospital stay (Estimate: -.99). Immediate full diet had no impact on the development of ileus (OR: .33). CONCLUSIONS: An immediate postoperative full diet following an anterior approach to the lumbar spine was not found to be associated with an increased risk of postoperative ileus in patients deemed appropriate for early diet liberalization. Moreover, an early full diet was found to reduce length of hospitalization and risk of postoperative urinary retention. Reconsideration of postoperative diet protocols may help optimize patient outcomes and recovery.

Lateral approach to the lumbar spine: The utility of an access surgeon.

Background: Lateral lumbar interbody fusions (LLIFs) utilize a retroperitoneal approach that avoids the intraperitoneal organs and manipulation of the anterior vasculature encountered in anterior approaches to the lumbar spine. The approach was championed by spinal surgeons; however, general/vasculature surgeons may be more comfortable with the approach. Objective: The objective of this study was to compare short-term outcomes following LLIF procedures based on whether a spine surgeon or access surgeon performed the approach. Materials and Methods: We retrospectively identified all one- to two-level LLIFs at a tertiary care center from 2011 to 2021 for degenerative spine disease. Patients were divided into groups based on whether a spine surgeon or general surgeon performed the surgical approach. The electronic medical record was reviewed for hospital readmissions and complication rates. Results: We identified 239 patients; of which 177 had approaches performed by spine surgeons and 62 by general surgeons. The spine surgeon group had fewer levels with posterior instrumentation (1.40 vs. 2.00; P < 0.001) and decompressed (0.94 vs. 1.25, P = 0.046); however, the two groups had a similar amount of two-level LLIFs (29.9% vs. 27.4%, P = 0.831). This spine surgeon approach group was found to have shorter surgeries (281 vs. 328 min, P = 0.002) and shorter hospital stays Length of Stay (LOS) (3.1 vs. 3.6 days, P = 0.019); however, these differences were largely attributed to the shorter posterior fusion construct. On regression analysis, there was no statistical difference in postoperative complication rates whether or not an access surgeon was utilized (P = 0.226). Conclusion: Similar outcomes may be seen regardless of whether a spine or access surgeon performs the approach for an LLIF.

atm Mutation and Oxidative Stress Enhance the Pre-Cancerous Effects of UHRF1 Overexpression in Zebrafish Livers.

The ataxia-telangiectasia mutated (atm) gene is activated in response to genotoxic stress and leads to activation of the tp53 tumor suppressor gene which induces either senescence or apoptosis as tumor suppressive mechanisms. Atm also serves non-canonical functions in the response to oxidative stress and chromatin reorganization. We previously reported that overexpression of the epigenetic regulator and oncogene Ubiquitin Like with PHD and Ring Finger Domains 1 (UHRF1) in zebrafish hepatocytes resulted in tp53-dependent hepatocyte senescence, a small liver and larval lethality. We investigated the role of atm on UHRF1-mediated phenotypes by generating zebrafish atm mutants. atm-/- adults were viable but had reduction in fertility. Embryos developed normally but were protected from lethality caused by etoposide or H2O2 exposure and failed to fully upregulate Tp53 targets or oxidative stress response genes in response to these treatments. In contrast to the finding that Tp53 prevents the small liver phenotype caused by UHRF1 overexpression, atm mutation and exposure to H2O2 further reduced the liver size in UHRF1 overexpressing larvae whereas treatment with the antioxidant N-acetyl cysteine suppressed this phenotype. We conclude that UHRF1 overexpression in hepatocytes causes oxidative stress, and that loss of atm further enhances this, triggering elimination of these precancerous cells, leading to a small liver.

Surrogate-based Optimization of Capture Chromatography Platforms for the Improvement of Computational Efficiency.

In this work, we discuss the use of surrogate functions and a new optimization framework to create an efficient and robust computational framework for process design. Our model process is the capture chromatography unit operation for monoclonal antibody purification, an important step in biopharmaceutical manufacturing. Simulating this unit operation involves solving a system of non-linear partial differential equations, which can have high computational cost. We implemented surrogate functions to reduce the computational time and make the framework more attractive for industrial applications. This strategy yielded accurate results with a 93% decrease in processing time. Additionally, we developed a new optimization framework to reduce the number of simulations needed to generate a solution to the optimization problem. We demonstrate the performance of our new framework, which uses MATLAB built-in tools, by comparing its performance against individual optimization algorithms for problems with integer, continuous, and mixed-integer variables.

Computational framework for the techno-economic analysis of monoclonal antibody capture chromatography platforms.

We developed a computational framework that integrates commercial software components to perform customizable technoeconomic feasibility analyses. The use of multiple software packages overcomes the shortcomings of each to provide a detailed simulation that can be used for sensitivity analyses and optimizations. In this paper, the framework was used to evaluate the performance of monoclonal antibody capture processes. To this end, the simulation framework incorporated dynamic models for the affinity chromatography step that were validated with experimental breakthrough curves. The results were integrated with an Intelligen SuperPro Designer process simulation for the evaluation of key performance indicators of the operations. As proof of concept, the framework was used to perform a sensitivity analysis and optimization for a case study in which we sought to compare membrane and resin chromatography for disposable and reusable batch capture platforms. Two membranes and one resin were selected for the capture media, which yielded six process alternatives to compare. The objective functions were set to be cost of goods, process time, and buffer utilization. The results of the optimization of these process alternatives were a set of operating conditions that display tradeoffs between competing objectives. From this application exercise, we conclude that the framework can handle multiple variables and objectives, and it is adaptable to platforms with different chromatography media and operating modes. Additionally, the framework is capable of providing ad hoc analyses for decision making in a specific production context.