Patawut Bovonratwet

Discriminative ability of commonly used indices to predict adverse outcomes after poster lumbar fusion: a comparison of demographics, ASA, the modified Charlson Comorbidity Index, and the modified Frailty Index

BACKGROUND CONTEXT As research tools, the American Society of Anesthesiologists (ASA) physical status classification system, the modified Charlson Comorbidity Index (mCCI), and the modified Frailty Index (mFI) have been associated with complications following spine procedures. However, with respect to clinical use for various adverse outcomes, no known study has compared the predictive performance of these indices specifically following posterior lumbar fusion (PLF). PURPOSE This study aimed to compare the discriminative ability of ASA, mCCI, and mFI, as well as demographic factors including age, body mass index, and gender for perioperative adverse outcomes following PLF. STUDY DESIGN/SETTING A retrospective review of prospectively collected data was performed. PATIENT SAMPLE Patients undergoing elective PLF with or without interbody fusion were extracted from the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program (NSQIP). OUTCOME MEASURES Perioperative adverse outcome variables assessed included the occurrence of minor adverse events, severe adverse events, infectious adverse events, any adverse event, extended length of hospital stay, and discharge to higher-level care. METHODS Patient comorbidity indices and characteristics were delineated and assessed for discriminative ability in predicting perioperative adverse outcomes using an area under the curve analysis from the receiver operating characteristics curves. RESULTS In total, 16,495 patients were identified who met the inclusion criteria. The most predictive comorbidity index was ASA and demographic factor was age. Of these two factors, age had the larger discriminative ability for three out of the six adverse outcomes and ASA was the most predictive for one out of six adverse outcomes. A combination of the most predictive demographic factor and comorbidity index resulted in improvements in discriminative ability over the individual components for five of the six outcome variables. CONCLUSION For PLF, easily obtained patient ASA and age have overall similar or better discriminative abilities for perioperative adverse outcomes than numerically tabulated indices that have multiple inputs and are harder to implement in clinical practice.

Metabolic glycoengineering sensitizes drug-resistant pancreatic cancer cells to tyrosine kinase inhibitors erlotinib and gefitinib

Metastatic human pancreatic cancer cells (the SW1990 line) that are resistant to the EGFR-targeting tyrosine kinase inhibitor drugs (TKI) erlotinib and gefitinib were treated with 1,3,4-O-Bu3ManNAc, a “metabolic glycoengineering” drug candidate that increased sialylation by ∼12-fold. Consistent with genetic methods previously used to increase EGFR sialylation, this small molecule reduced EGF binding, EGFR transphosporylation, and downstream STAT activation. Significantly, co-treatment with both the sugar pharmacophore and the existing TKI drugs resulted in strong synergy, in essence re-sensitizing the SW1990 cells to these drugs. Finally, l,3,4-O-Bu3ManNAz, which is the azido-modified counterpart to l,3,4-O-Bu3ManNAc, provided a similar benefit thereby establishing a broad-based foundation to extend a “metabolic glycoengineering” approach to clinical applications.

Metabolic flux-driven sialylation alters internalization, recycling, and drug sensitivity of the epidermal growth factor receptor (EGFR) in SW1990 pancreatic cancer cells

In prior work we reported that advanced stage, drug-resistant pancreatic cancer cells (the SW1990 line) can be sensitized to the EGFR-targeting tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib by treatment with 1,3,4-O-Bu3ManNAc (Bioorg. Med. Chem. Lett. (2015) 25(6):1223-7). Here we provide mechanistic insights into how this compound inhibits EGFR activity and provides synergy with TKI drugs. First, we showed that the sialylation of the EGFR receptor was at most only modestly enhanced (by ∼20 to 30%) compared to overall ∼2-fold increase in cell surface levels of this sugar. Second, flux-driven sialylation did not alter EGFR dimerization as has been reported for cancer cell lines that experience increased sialylation due to spontaneous mutations. Instead, we present evidence that 1,3,4-O-Bu3ManNAc treatment weakens the galectin lattice, increases the internalization of EGFR, and shifts endosomal trafficking towards non-clathrin mediated (NCM) endocytosis. Finally, by evaluating downstream targets of EGFR signaling, we linked synergy between 1,3,4-O-Bu3ManNAc and existing TKI drugs to a shift from clathrin-coated endocytosis (which allows EGFR signaling to continue after internalization) towards NCM endocytosis, which targets internalized moieties for degradation and thereby rapidly diminishes signaling.

Different Fusion Approaches for Single-level Lumbar Spondylolysis Have Similar Perioperative Outcomes

Study Design. Retrospective cohort study Objective. The aim of this study was to compare perioperative adverse events for patients with lumbar spondylolysis treated with transforaminal lumbar interbody fusion (TLIF), posterior spinal fusion (PSF), combined anterior and posterior fusion (AP fusion), or anterior lumbar interbody fusion (ALIF). Summary of Background Data. Previous cohort studies have shown similar long-term outcomes for different surgical approaches for this indication, but potential differences in 30-day perioperative adverse events have not been well characterized. Methods. The present study uses data extracted from the American College of Surgeons National Surgical Quality Improvement Database. Patients undergoing fusion with different approaches for lumbar spondylolysis were identified. Propensity score matching was utilized to account for potential differences in demographic and comorbidity factors. Comparisons among perioperative outcomes were then made among the propensity score-matched study groups. Results. Of 1077 cases of spondylolysis identified, 556 underwent TLIF, 327 underwent PSF, 108 underwent AP fusion, and 86 underwent ALIF. After propensity score matching, there were no differences in the rates of any of the 30-day individual adverse events studied and no differences in the aggregated groupings of any adverse event, serious adverse event, or minor adverse event. There was a significantly increased operative time in the AP fusion group, but there were no differences in hospital length of stay or readmission rates. Conclusion. Because perioperative adverse event rates were similar, even with a slightly longer operative time in the AP fusion group, these findings suggest that surgeon preference and long-term outcomes are better used to determine the recommendation of one surgical approach over another for single level fusions for lumbar spondylolysis. Level of Evidence. 3

Glycoengineering of Esterase Activity through Metabolic Flux-Based Modulation of Sialic Acid

This report describes the metabolic glycoengineering (MGE) of intracellular esterase activity in human colon cancer (LS174T) and Chinese hamster ovary (CHO) cells. In silico analysis of carboxylesterases CES1 and CES2 suggested that these enzymes are modified with sialylated N‐glycans, which are proposed to stabilize the active multimeric forms of these enzymes. This premise was supported by treating cells with butanolylated ManNAc to increase sialylation, which in turn increased esterase activity. By contrast, hexosamine analogues not targeted to sialic acid biosynthesis (e.g., butanoylated GlcNAc or GalNAc) had minimal impact. Measurement of mRNA and protein confirmed that esterase activity was controlled through glycosylation and not through transcription or translation. Azide‐modified ManNAc analogues widely used in MGE also enhanced esterase activity and provided a way to enrich targeted glycoengineered proteins (such as CES2), thereby providing unambiguous evidence that the compounds were converted to sialosides and installed into the glycan structures of esterases as intended. Overall, this study provides a pioneering example of the modulation of intracellular enzyme activity through MGE, which expands the value of this technology from its current status as a labeling strategy and modulator of cell surface biological events.

Revision Total Knee Arthroplasty in Octogenarians: An Analysis of 957 Cases

BACKGROUND The number of octogenarians undergoing revision total knee arthroplasty (TKA) is increasing. However, there has been a lack of studies investigating the perioperative course and safety of revision TKA performed in this potentially vulnerable population in a large patient population. The purpose of this study is to compare complications following revision TKA between octogenarians and 2 younger patient populations (<70 and 70-79 year olds). METHODS Patients who underwent revision TKA were identified in the 2005-2015 National Surgical Quality Improvement Program database and stratified into 3 age groups: <70, 70-79, and ≥80 years. Baseline preoperative and intraoperative characteristics were compared between the 3 groups. Propensity score matched comparisons were then performed for 30-day perioperative complications, length of hospital stay, and readmissions. RESULTS This study included 6523 (<70 years), 2509 (70-79 years), and 957 octogenarian patients who underwent revision TKA. After propensity matching, statistical analysis revealed only higher rates of blood transfusion and slightly longer length of stay in octogenarians compared to <70 year olds. Similarly, octogenarians had only higher rates of blood transfusion and slightly longer length of stay compared to 70-79 year olds. Notably, there were no differences in mortality or readmission between octogenarians compared to younger populations. CONCLUSION These data suggest that revision TKA can safely be considered for octogenarians with the observation of higher rates of blood transfusion and slightly longer length of stay compared to younger populations. Octogenarian patients need not be discouraged from revision TKA solely based on their advanced age.

Evaluating the effect of growing patient numbers and changing data elements in the National Surgical Quality Improvement Program (NSQIP) database over the years: a study of posterior lumbar fusion outcomes

BACKGROUND CONTEXT The use of national databases in spinal surgery outcomes research is increasing. A number of variables collected by the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) changed between 2010 and 2011, coinciding with a rapid increase in the number of patients included per year. However, there has been limited study evaluating the effect that these changes may have on the results of outcomes studies. PURPOSE The present study aimed to investigate the influence of changing data elements and growth of the NSQIP database on results of lumbar fusion outcomes studies. STUDY DESIGN/SETTING This is a retrospective cohort study of prospectively collected data. PATIENT SAMPLE The NSQIP database was retrospectively queried to identify 19,755 patients who underwent elective posterior lumbar fusion surgery with or without interbody fusion between 2005 and 2014. Patients were split into two groups based on year of surgery: 2,802 from 2005 to 2010 and 16,953 from 2011 to 2014. OUTCOME MEASURES The occurrence of adverse events after discharge from the hospital, within postoperative day 30, was determined. METHODS Preoperative characteristics and 30-day perioperative outcomes were compared between the era groups using bivariate analysis. To illustrate the effect of such changing data elements, the association between age and postoperative outcomes in the era groups was analyzed using multivariate Poisson regression. The present study had no funding sources, and there were no study-related conflicts of interest for any authors. RESULTS There were significant differences between the era groups for a variety of preoperative characteristics. Postoperative events such blood transfusion and deep vein thrombosis were also significantly different between the era groups. For the 2005-2010 cohort, age was significantly associated with septic shock by multivariate analysis. For the 2011-2014 cohort, age was significantly associated with septic shock, urinary tract infection, blood transfusion, myocardial infarction, and extended length of stay. CONCLUSIONS The NSQIP database has undergone substantial changes between 2005 and 2014. These changes may contribute to different results in analyses, such as the association between age and postoperative outcomes, when using older versus newer data. Conclusions from early studies using this database may warrant reconsideration.

Dialysis is an independent risk factor for perioperative adverse events, readmission, reoperation, and mortality for patients undergoing elective spine surgery

BACKGROUND CONTEXT The prevalence of dialysis-dependent patients in the United States is growing. Prior studies evaluating the risk of perioperative adverse events for dialysis-dependent patients are either institutional cohort studies limited by patient numbers or administrative database studies limited to inpatient data. PURPOSE The present study uses a large, national sample with 30-day follow-up to investigate dialysis as risk factor for perioperative complications independent of patient demographics or comorbidities. STUDY DESIGN/SETTING This is a retrospective cohort study. PATIENT SAMPLE Patients undergoing elective spine surgery with or without dialysis from the 2005-2015 National Surgical Quality Improvement Program (NSQIP) database were included in the study. OUTCOME MEASURES Postoperative complications within 30 days and binomial reoperation, readmission, and mortality within 30 days were determined. METHODS The 2005-2015 NSQIP databases were queried for adult dialysis-dependent and dialysis-independent patients undergoing elective spinal surgery. Differences in 30-day outcomes were compared using risk-adjusted multivariate regression and coarsened exact matching analysis for adverse events, unplanned readmission, reoperation, and mortality. The percentage of complications occurring before versus after hospital discharge was also assessed. The authors have no financial disclosures related to the present study. RESULTS A total of 467 dialysis and 173,311 non-dialysis patients met the inclusion criteria. Controlling for age, gender, body mass index, functional status, and American Society of Anesthesiologists (ASA) class, dialysis patients were found to be at significantly greater odds of any adverse event (odds ratio [OR]=2.52 before, 2.17 after matching, p=<.001), major adverse event (OR=2.90 before, 2.52 after matching, p=<.001), and minor adverse event (OR=1.50 before matching, p=<.025, but not significantly different after matching). Further, dialysis patients were significantly more likely to return to the operating room (OR=2.77 before, 2.50 after matching, p=<.001), have unplanned readmissions (OR=2.73 before, 2.37 after matching, p=<.001), and die within 30 days (OR=3.77 before, 2.71 after matching, p=<.001). Adverse events occurred after discharge for 51.78% of non-dialysis patients and for 43.80% of dialysis patients. CONCLUSIONS Dialysis patients undergoing elective spine surgery are at significantly higher risk of aggregated adverse outcomes, return to the operating room, readmission, and death than non-dialysis patients, even after controlling for patient demographics and overall health (as indicated by ASA class). These differences need to be considered when determining treatment options. Additionally, with bundled payments expected in spine surgery, physicians and hospitals need to account for increased costs and liabilities when working with dialysis patients.

Incidence and Considerations of 90 day Readmissions following Posterior Lumbar Fusion

BACKGROUND CONTEXT Posterior lumbar fusion (PLF) is a commonly performed procedure. The evolution of bundled payment plans is beginning to require physicians to more closely consider patient outcomes up to 90 days after an operation. Current quality metrics and other databases often consider only 30 postoperative days. The relatively new Healthcare Cost and Utilization Project Nationwide Readmissions Database (HCUP-NRD) tracks patient-linked hospital admissions data for up to one calendar year. PURPOSE To identify readmission rates within 90 days of discharge following PLF and to put this in context of 30 day readmission and baseline readmission rates. STUDY DESIGN Retrospective study of patients in the HCUP-NRD. PATIENT SAMPLE Any patient undergoing PLF performed in the first 9 months of 2013 were identified in the HCUP-NRD. OUTCOME MEASURES Readmission patterns up to a full calendar year after discharge. METHODS PLFs performed in the first 9 months of 2013 were identified in the HCUP-NRD. Patient demographics and readmissions were tracked for 90 days after discharge. To estimate the average admission rate in an untreated population, the average daily admission rate in the last quarter of the year was calculated for a subset of PLF patients who had their operation in the first quarter of the year. This study was deemed exempt by the institutions Human Investigation Committee. RESULTS Of 26,727 PLFs, 1,580 patients (5.91%) were readmitted within 30 days of discharge and 2,603 patients (9.74%) were readmitted within 90 days of discharge. Of all readmissions within 90 days, 54.56% occurred in the first 30 days. However, if only counting readmissions above the baseline admission rate of a matched population from the 4th quarter of the year (0.08% of population/day), 89.78% of 90 day readmissions occurred within the first 30 days. CONCLUSIONS The current study delineates readmission rates after PLF and puts this in the context of 30-day readmission rates and baseline readmission rates for those undergoing PLF. These results are important for patient counseling, planning, and preparing for potential bundled payments in spine surgery.

Total Disc Arthroplasty Versus Anterior Interbody Fusion in the Lumbar Spine Have Relatively a Few Differences in Readmission and Short-term Adverse Events

Study Design. Retrospective matched cohort study of prospectively collected data. Objective. To compare rates of adverse events and readmission between lumbar total disc arthroplasty (TDA) and anterior lumbar interbody fusion (ALIF) using the American College of Surgeons National Surgical Quality Improvement Program database. Summary of Background Data. TDA and ALIF may be considered for similar degenerative indications. However, there have been a few large-cohort comparison studies of short-term clinical outcomes for these procedures. Methods. The 2011−2015 NSQIP databases were retrospectively queried to identify patients who underwent elective stand-alone ALIF and TDA. After propensity matching, the association of procedure type with adverse events and readmission was determined using McNemars test. Operative time and postoperative length of stay (LOS) were compared using multivariate linear regression. Risk factors for adverse events were determined using multivariate Poisson regression. Results. In total, 1801 ALIF and 255 TDA patients were identified. After matching with propensity scores, there were no significant differences in the rates of any adverse event, serious adverse events, individual adverse events, or readmission other than blood transfusion, which occurred more frequently in the ALIF cohort (3.92% vs. 0.39%, P = 0.007). Operative time was not significantly different between the two cohorts, but postoperative LOS was significantly longer for ALIF cases (+0.28 days, P < 0.001). When evaluating 10 preoperative variables as potential risk factors for adverse events and readmission after TDA and ALIF, the majority of results were similar. Conclusion. The only identified differences in perioperative outcomes between TDA and ALIF were a 3.53% higher incidence of blood transfusion and 0.28-day longer LOS for the ALIF group. These results suggest overall similar short-term general-health outcomes between the two groups, and that the choice between the two procedures, for the appropriately selected patient, should be based on longer-term functional outcomes. Level of Evidence: 3