5-Year Revision Rates After Elective Multilevel Lumbar/Thoracolumbar Instrumented Fusions in Older Patients: An Analysis of State Databases.

OBJECTIVE: The purpose of this study wasto evaluate cause-specific 5-year revision rates and risk factors for revision after elective multilevel lumbar instrumented fusion in older patients. METHODS: Older patients (>60 years) who underwent elective multilevel (3+) lumbar instrumented fusions were identified in Healthcare Cost and Utilization Project state inpatient databases and followed for 5 years for revision operations because of mechanical failure, degenerative disease (DD), infection, postlaminectomy syndrome, and stenosis. Cox proportional hazards multivariate analyses were conducted to determine risk factors associated with revision for each diagnostic cause. RESULTS: The cohort included 5,636 patients (female-3,285; average age-71.6 years). Most of the operations were 3 to 7 levels (97.4%), and the mean length of stay was 5.4 days. The overall 5-year revision rate was 16.5% with predominant etiologies of DD (50.7%), mechanical failure (32.2%), and stenosis (8.0%). The revision procedure at the index operation was associated with an increased revision risk for DD (hazards ratio [HR] = 1.59, 95% confidence interval [CI], 1.29 to 1.98, P < 0.001) and mechanical failure (HR = 1.56, 95% CI, 1.19 to 2.04, P = 0.020). Male sex was associated with a significantly reduced revision risk for DD (HR = 0.75, 95% CI, 0.62 to 0.91, P = 0.04). Age, race, and number of comorbidities had no notable effect on the overall or cause-specific risk of revision. DISCUSSION: In this large database analysis, DD and mechanical failure were the most common etiologies comprising a 5-year revision rate of 16.5% after elective multilevel lumbar instrumented fusion in older patients. Revision operations and female patients carried the strongest risks for revision.

Rates and risk factors associated with 30- and 90-day readmissions and reoperations after spinal fusions for adult lumbar degenerative pathology and spinal deformity.

PURPOSE: Analyze state databases to determine variables associated with of short-term readmissions and reoperations following thoracolumbar spine fusions for degenerative pathology and spinal deformity. METHODS: Retrospective study of State Inpatient Database (2005-13, CA, NE, NY, FL, NC, UT). INCLUSION CRITERIA: age > 45 years, diagnosis of degenerative spinal deformity, ≥ 3 level posterolateral lumbar spine fusion. EXCLUSION CRITERIA: revision surgery, cervical fusions, trauma, and cancer. Univariate and step-wise multivariate logistic regression analyses were performed to identify independent variables associated with of 30- and 90-day readmissions and reoperations. RESULTS: 12,641 patients were included. All-cause 30- and 90-day readmission rates were 14.6% and 21.1%, respectively. 90-day readmissions were associated with: age > 80 (OR: 1.42), 8 + level fusions (OR: 1.19), hospital length of stay (LOS) > 7 days (OR: 1.43), obesity (OR: 1.29), morbid obesity (OR: 1.66), academic hospital (OR: 1.13), cancer history (OR:1.21), drug abuse (OR: 1.31), increased Charlson Comorbidity index (OR: 1.12), and depression (OR: 1.20). Private insurance (OR: 0.64) and lumbar-only fusions (OR: 0.87) were not associated with 90-day readmissions. All-cause 30- and 90-day reoperation rates were 1.8% and 4.2%, respectively. Variables associated with 90-day reoperations were 8 + level fusions (OR: 1.28), LOS > 7 days (OR: 1.43), drug abuse (OR: 1.68), osteoporosis (OR: 1.26), and depression (OR: 1.23). Circumferential fusion (OR: 0.58) and lumbar-only fusions (OR: 0.68) were not associated with 90-day reoperations. CONCLUSIONS: 30- and 90-day readmission and reoperation rates in thoracolumbar fusions for adult degenerative pathology and spinal deformity may have been underreported in previously published smaller studies. Identification of modifiable risk factors is important for improving quality of care through preoperative optimization.

Antibody-receptor interactions mediate antibody-dependent cellular cytotoxicity.

Binding of antibodies to their receptors is a core component of the innate immune system. Understanding the precise interactions between antibodies and their Fc receptors has led to the engineering of novel mAb biotherapeutics with tailored biological activities. One of the most significant findings is that afucosylated monoclonal antibodies demonstrate increased affinity toward the receptor FcγRIIIa, with a commensurate increase in antibody-dependent cellular cytotoxicity. Crystal structure analysis has led to the hypothesis that afucosylation in the Fc region results in reduced steric hindrance between antibody-receptor intermolecular glycan interactions, enhancing receptor affinity; however, solution-phase data have yet to corroborate this hypothesis. In addition, recent work has shown that the fragment antigen-binding (Fab) region may directly interact with Fc receptors; however, the biological consequences of these interactions remain unclear. By probing differences in solvent accessibility between native and afucosylated immunoglobulin G1 (IgG1) using hydroxyl radical footprinting-MS, we provide the first solution-phase evidence that an IgG1 bearing an afucosylated Fc region appears to require fewer conformational changes for FcγRIIIa binding. In addition, we performed extensive molecular dynamics (MD) simulations to understand the molecular mechanism behind the effects of afucosylation. The combination of these techniques provides molecular insight into the steric hindrance from the core Fc fucose in IgG1 and corroborates previously proposed Fab-receptor interactions. Furthermore, MD-guided rational mutagenesis enabled us to demonstrate that Fab-receptor interactions directly contribute to the modulation of antibody-dependent cellular cytotoxicity activity. This work demonstrates that in addition to Fc-polypeptide and glycan-mediated interactions, the Fab provides a third component that influences IgG-Fc receptor biology.

Perioperative Serum 25-Hydroxyvitamin D Levels as a Predictor of Postoperative Opioid Use and Opioid Use Disorder: a Cohort Study.

IMPORTANCE: Vitamin D deficiency is associated with chronic pain syndromes and higher opioid use among cancer patients, but its association with opioid use among opioid-naïve subjects following a major surgical procedure with acute pain has not been explored. OBJECTIVE: To determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels, opioid use, and opioid use disorder. METHODS: We identified commercially insured subjects aged 18-64 years with available perioperative serum 25-hydroxyvitamin D (25D) levels who underwent one of nine major surgical procedures in 2000-2014. Primary outcomes were dose and duration of opioid use measured using pharmacy claims. Secondary outcome was opioid use disorder captured using diagnosis codes. Multivariable negative binomial models with generalized estimating equations were performed examining the association between 25D levels and postoperative opioid use measures, adjusting for age, sex, race/ethnicity, Charlson score, education, income, latitude, and season of blood draw. Adjusted Cox regression was used to examine the association with opioid use disorder. RESULTS: Among 5446 subjects, serum 25(OH)D was sufficient (≥ 20 ng/mL) among 4349 (79.9%) subjects, whereas 837 (15.4%) had insufficient (12 to < 20 ng/mL) and 260 (4.8%) had deficient (< 12 ng/mL) levels. On multivariable analysis, as compared with subjects with sufficient 25(OH)D levels, subjects with deficient 25(OH)D levels had 1.7 more days (95% CI 0.76, 2.58) of opioid use per year and had 98.7 higher morphine milligram equivalent dose (95% CI 55.7, 141.8) per year. Among 11,713 study cohort, subjects with deficient 25(OH)D levels were more likely to be diagnosed with opioid use disorders (HR 2.41; 95% CI 1.05, 5.52). CONCLUSION: Patients undergoing common surgical procedures with deficient 25D levels are more likely to have higher opioid use and an increased risk of opioid use disorder compared to those with sufficient levels. Serum 25D levels may serve as a biomarker to identify subjects at increased risk of opioid misuse.

Impact of high-deductible insurance on adjuvant hormonal therapy use in breast cancer.

OBJECTIVE: High-deductible health plans (HDHPs) have become the predominant commercial health insurance arrangement in the US. HDHPs require substantial out-of-pocket (OOP) costs for most services but often exempt medications from high cost sharing. We examined effects of HDHPs on OOP costs and utilization of adjuvant hormonal therapy (AHT), which are fundamental care for patients with breast cancer. METHODS: This controlled quasi-experimental study used claims data (2003-2012) from a large national health insurer. We included 986 women with incident early-stage breast cancer, age 25-64 years, insured by employers that mandated a transition from low-deductible (≤ $500/year) to high-deductible (≥ $1000/year) coverage, and 3479 propensity score-matched controls whose employers offered only low-deductible plans. We examined AHT utilization and OOP costs per person-year before and after the HDHP switch. RESULTS: At baseline, the OOP costs for AHT were $40.41 and $36.55 per person-year among the HDHP and control groups. After the HDHP switch, the OOP costs for AHT were $91.76 and $72.98 per person-year among the HDHP and control groups, respectively. AHT OOP costs increased among HDHP members relative to controls but the change was not significant (relative change 13.72% [95% CI - 9.25, 36.70%]). AHT use among HDHP members did not change compared to controls (relative change of 2.73% [95% CI - 14.01, 19.48%]); the change in aromatase inhibitor use was - 11.94% (95% CI - 32.76, 8.88%) and the change in tamoxifen use was 20.65% (95% CI - 8.01, 49.32%). CONCLUSION: We did not detect significant changes in AHT use after the HDHP switch. Findings might be related to modest increases in overall AHT OOP costs, the availability of low-cost generic tamoxifen, and patient awareness that AHT can prolong life and health. Minimizing OOP cost increases for essential medications might represent a feasible approach for maintaining medication adherence among HDHP members with incident breast cancer.

The Anesthesia Perioperative "Call for Help"-Experience at a Quaternary Pediatric Medical Center: Analysis of 67,564 Anesthesia Encounters.

BACKGROUND: During the past several decades, anesthesia has become increasingly safe. Truly major adverse events are rare, and anesthesia quality researchers have instituted programs to evaluate "near miss" or less critical adverse events to evaluate the safety of anesthesia delivery. In this study, we aimed to evaluate calls for emergency help in our institution as a surrogate for pending critical events. We hypothesized that calls would be more common in patients with high American Society of Anesthesiologists (ASA) physical status, history of prematurity, and children with recent respiratory illness compared to those without these characteristics. METHODS: We analyzed emergent calls for help initiated by perioperative personnel ("STAT" calls) between August 2011 and September 2015 at Boston Children's Hospital. Our analysis had 2 phases: (1) All 193 STAT calls that occurred during this time period were analyzed for demographic variables (age, ASA physical status, gender) and specific features of the STAT calls (provider who initiated the call, anesthetic phase, presence of recent respiratory illness, location). We further categorized the STAT calls as "complicated" or "uncomplicated" based on an unexpected change in patient disposition, and analyzed how demographic factors and specific features related to the likelihood of a STAT call being complicated. (2) A subset of the total calls (108), captured after introduction of electronic intraoperative medical record in July 2012, were analyzed for the incidence of STAT calls by comparing the number and nature of the STAT calls to the number of surgical/diagnostic procedures performed. RESULTS: Univariable and multivariable analysis of the entire cohort of STAT calls (193 cases) identified several characteristics that were more likely to be associated with a complicated STAT call: higher ASA physical status; history of respiratory illness; cardiac inciting event; occurrence during induction phase of general anesthesia; postanesthesia care unit location; and calls initiated by an attending physician or a pediatric anesthesia fellow. Multivariable analysis of the subset of 108 indicated that age <1 year and a history of prematurity were independent predictors of a higher incidence of STAT calls. Offsite anesthesia services were associated with a lower frequency of STAT calls independent of the other variables. CONCLUSIONS: Our study offers the most comprehensive analysis of emergent perioperative calls for help in pediatric anesthesia to date. We identified several characteristics, independently associated with more complicated and frequent perioperative STAT calls. Further research is required to evaluate the utility of this information in preventing and treating adverse events in children undergoing surgery and anesthesia.