Citations

Study Design. This study retrospectively analyzes prospectively collected data. Objective. The primary aim of this study is to present a scheme for patient-reported outcome (PRO)-based, risk-adjusted rankings of spine surgeons and sites that perform elective lumbar surgery, using the Quality and Outcomes Database (QOD). Summary of Background Data. There is currently no means of determining which spine surgeons or centers are positive or negative outliers with respect to PROs for elective lumbar surgery. This is a critical gap as we move toward a value-based model of health care in which providers assume more accountability for the effectiveness of their treatments. Methods. Random effects regression models were fit for the following outcomes, with QOD site as a fixed effect but surgeon ID as a random effect: Oswestry Disability Index, EQ-5D, back pain and leg pain, and satisfaction. Hierarchical Bayesian models were also fit for each outcome, with QOD site as a random effect and surgeon as a nested random effect. Results. Our study cohort consists of 8834 patients who underwent surgery by 124 QOD surgeons, for the degenerative lumbar diseases. Nonoverlapping Bayesian credible intervals demonstrate that the variance attributed to QOD site was greater than the nested variance attributed to surgeon ID for the included PROs. Conclusion. This study presents a novel strategy for the risk-adjusted, PRO-based ranking of spine surgeons and practices. This can help identify positive and negative outliers, thereby forming the basis for large-scale quality improvement. Assuming adequate coverage of baseline risk adjustment, the choice of surgeon matters when considering PROs after lumbar surgery; however, the choice of site appears to matter more. Level of Evidence: 3

BACKGROUND: Previous studies on readmissions after left ventricular assist device (LVAD) implantation have focused on hospital readmissions after dismissal from the index hospitalization. Because few data exist, the purpose of this study was to examine intensive care unit (ICU) readmissions in patients during their initial hospitalization for LVAD implantation to determine reasons for, factors associated with, and incidence of mortality after ICU readmission. METHODS: A retrospective analysis was performed from February 2007 to March 2015 of patients at our institution receiving first-time LVAD implantation. After LVAD implantation, patients dismissed from the ICU who then required ICU readmission before hospital dismissal were compared to those not requiring ICU readmission before hospital dismissal with respect to preoperative, intraoperative, and postoperative factors. RESULTS: Among 287 LVAD patients, 266 survived their initial ICU admission, of which 49 (18.4%) required ICU readmission. The most common reasons for readmission were bleeding and respiratory failure. Factors found to be univariably associated with ICU readmission were preoperative hemoglobin, preoperative aspartate aminotransferase, preoperative atrial fibrillation, preoperative dialysis, longer cardiopulmonary bypass times, and higher intraoperative allogeneic blood transfusion requirements. Multivariable analysis revealed ICU readmission to be independently associated with preoperative dialysis (odds ratio, 12.86; 95% confidence interval, 3.16–52.28; P < .001). Overall mortality at 1 year was 22.6%. Survival after hospital dismissal was worse for patients who required ICU readmission during the index hospitalization (adjusted hazard ratio, 2.35; 95% confidence interval, 1.15–4.81; P = .019). CONCLUSIONS: ICU readmission after LVAD implantation occurred relatively frequently and was significantly associated with 1-year mortality after hospital dismissal. These data can perhaps be used to identify subsets of LVAD patients at risk for ICU readmission and may lead to implementation of practice changes to mitigate ICU readmissions. Future larger and prospective studies are warranted.

Study Design. This study retrospectively analyzes prospectively collected data. Objective. Here we aim to develop predictive models for 3-month medical and surgical readmission after elective lumbar surgery, based on a multi-institutional, national spine registry. Summary of Background Data. Unplanned readmissions place considerable stress on payers, hospitals, and patients. Medicare data reveals a 30-day readmission rate of 7.8% for lumbar-decompressions and 13.0% for lumbar-fusions, and hospitals are now being penalized for excessive 30-day readmission rates by virtue of the Hospital Readmissions Reduction Program. Methods. The Quality and Outcomes Database (QOD) was queried for patients undergoing elective lumbar surgery for degenerative diseases. The QOD prospectively captures 3-month readmissions through electronic medical record (EMR) review and self-reported outcome questionnaires. Distinct multivariable logistic regression models were fitted for surgery-related and medical readmissions adjusting for patient and surgery-specific variables. Results. Of the total 33,674 patients included in this study 2079 (6.15%) reported at least one readmission during the 90-day postoperative period. The odds of medical readmission were significantly higher for older patients, males versus females, African Americans versus Caucasion, those with higher American Society of Anesthesiologists (ASA) grade, diabetes, coronary artery disease, higher numbers of involved levels, anterior only or anterior–posterior versus posterior approach; also, for patients who were unemployed compared with employed patients and those with high baseline Oswestry Disability Index (ODI). The odds of surgery-related readmission were significantly greater for patients with a higher body mass index (BMI), a higher ASA grade, female versus male, and African Americans versus Caucasians; also, for patients with severe depression, more involved spinal levels, anterior-only surgical approaches and higher baseline ODI scores. Conclusion. In this study we present internally validated predictive models for medical and surgical readmission after elective lumbar spine surgery. These findings set the stage for targeted interventions with a potential to reduce unnecessary readmissions, and also suggest that medical and surgical readmissions be treated as distinct clinical events. Level of Evidence: 3

Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-transcriptional regulators of senescence-associated (SA) genes. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet ( n = 6 each). Next-generation miRNA sequencing (miRNA-seq) was performed to identify miRNAs up-or down-regulated in MetS-MSCs compared with Lean-MSCs. Functional pathways of SA genes targeted by miRNAs were analyzed using gene ontology. MSC senescence was evaluated by p16 and p21 immunoreactivity, H2AX protein expression, and SA-β-Galactosidase activity. In addition, gene expression of p16, p21, MAPK3 (ERK1) and MAPK14, and MSC migration were studied after inhibition of SA-miR-27b. Senescence biomarkers were significantly elevated in MetS-MSCs. We found seven upregulated miRNAs, including miR-27b, and three downregulated miRNAs in MetS-MSCs, which regulate 35 SA genes, particularly MAPK signaling. Inhibition of miR-27b in cultured MSCs downregulated p16 and MARP3 genes, and increased MSC migration. MetS modulates MSC expression of SA-miRNAs that may regulate their senescence, and the p16 pathway seems to play an important role in MetS-induced MSC senescence.

Abstract CCGA [NCT02889978] is the largest study of cfDNA-based early cancer detection; the first CCGA learnings from multiple cfDNA assays are reported here. This prospective, multi-center, observational study has enrolled 10,012 of 15,000 demographically-balanced participants at 141 sites. Blood was collected from participants with newly diagnosed therapy-naive cancer (C, case) and participants without a diagnosis of cancer (noncancer [NC], control) as defined at enrollment. This preplanned substudy included 878 cases, 580 controls, and 169 assay controls (n=1627) across 20 tumor types and all clinical stages. All samples were analyzed by: 1) Paired cfDNA and white blood cell (WBC)-targeted sequencing (60,000X, 507 gene panel); a joint caller removed WBC-derived somatic variants and residual technical noise; 2) Paired cfDNA and WBC whole-genome sequencing (WGS; 35X); a novel machine learning algorithm generated cancer-related signal scores; joint analysis identified shared events; and 3) cfDNA whole-genome bisulfite sequencing (WGBS; 34X); normalized scores were generated using abnormally methylated fragments. In the targeted assay, non-tumor WBC-matched cfDNA somatic variants (SNVs/indels) accounted for 76% of all variants in NC and 65% in C. Consistent with somatic mosaicism (i.e., clonal hematopoiesis), WBC-matched variants increased with age; several were non-canonical loss-of-function mutations not previously reported. After WBC variant removal, canonical driver somatic variants were highly specific to C (e.g., in EGFR and PIK3CA, 0 NC had variants vs 11 and 30, respectively, of C). Similarly, of 8 NC with somatic copy number alterations (SCNAs) detected with WGS, 4 were derived from WBCs. WGBS data revealed informative hyper- and hypo-fragment level CpGs (1:2 ratio); a subset was used to calculate methylation scores. A consistent “cancer-like” signal was observed in &lt;1% of NC participants across all assays (representing potential undiagnosed cancers). An increasing trend was observed in NC vs stages I-III vs stage IV (nonsyn. SNVs/indels per Mb [Mean±SD] NC: 1.01±0.86, stages I-III: 2.43±3.98; stage IV: 6.45±6.79; WGS score NC: 0.00±0.08, I-III: 0.27±0.98; IV: 1.95± 2.33; methylation score NC: 0±0.50; I-III: 1.02±1.77; IV: 3.94±1.70). These data demonstrate the feasibility of achieving &gt;99% specificity for invasive cancer, and support the promise of cfDNA assay for early cancer detection. Additional data will be presented on detected plasma:tissue variant concordance and on multi-assay modeling. Citation Format: Alexander A. Aravanis, Geoffrey R. Oxnard, Tara Maddala, Earl Hubbell, Oliver Venn, Arash Jamshidi, Ling Shen, Hamed Amini, John A. Beausang, Craig Betts, Daniel Civello, Konstantin Davydov, Saniya Fazullina, Darya Filippova, Sante Gnerre, Samuel Gross, Chenlu Hou, Roger Jiang, Byoungsok Jung, Kathryn Kurtzman, Collin Melton, Shivani Nautiyal, Jonathan Newman, Joshua Newman, Cosmos Nicolaou, Richard Rava, Onur Sakarya, Ravi Vijaya Satya, Seyedmehdi Shojaee, Kristan Steffen, Anton Valouev, Hui Xu, Jeanne Yue, Nan Zhang, Jose Baselga, Rosanna Lapham, Daron G. Davis, David Smith, Donald Richards, Michael V. Seiden, Charles Swanton, Timothy J. Yeatman, Robert Tibshirani, Christina Curtis, Sylvia K. Plevritis, Richard Williams, Eric Klein, Anne-Renee Hartman, Minetta C. Liu. Development of plasma cell-free DNA (cfDNA) assays for early cancer detection: first insights from the Circulating Cell-Free Genome Atlas Study (CCGA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-343.

The rodent model of folic acid (FA)-induced acute kidney injury (AKI) provides a useful model for studying human AKI, but little is known about longitudinal changes in renal hemodynamics and evolution of renal fibrosis in vivo. In this work, we aimed to longitudinally assess renal structural and functional changes using multiparametric magnetic resonance imaging (MRI). Ten adult mice were injected with FA, after which a multiparametric MRI was used to measure kidney volume, hypoxia index R2*, magnetization transfer ratio (MTR), perfusion, T1, and glomerular filtration rate (GFR) at 2 wk posttreatment. Then five mice were euthanized for histology, and the other five underwent MRI again at 4 wk, followed by histology. Control mice ( n = 5) were injected with vehicle and studied with MRI at 2 wk. Trichrome and hematoxylin-eosin staining were performed to assess FA-induced tissue injuries. Whereas kidney size and oxygenation showed progressive deterioration, a transient impairment in renal perfusion and normalized GFR slightly improved by 4 wk. Kidney fluid content, as reflected by T1, was prominent at 2 wk and tended to regress at 4 wk, consistent with observed tubular dilation. Trichrome staining revealed patchy necrosis and mild interstitial fibrosis at 2 wk, which exacerbated at 4 wk. MTR detected increased fibrosis at 4 wk. In conclusion, multiparametric MRI captured the longitudinal progression in kidney damage evolving within the first month after treatment with folic acid and may provide a useful tool for assessment of therapeutic strategies.

Abstract BACKGROUND Reducing length of stay (LOS) in a safe manner has the potential to save significant costs for the care of patients undergoing elective lumbar spine surgery. Due to the relative absence on weekends of staff required for discharging patients to rehabilitation or nursing facilities, we hypothesize that patients undergoing lumbar surgery later in the week have a longer LOS than their counterparts. OBJECTIVE To analyze the effect of day of the week for lumbar surgery on LOS. METHODS Patients undergoing surgery for lumbar degenerative disease were prospectively enrolled in the multicenter quality and outcomes database registry. A multivariable proportional odds regression model was built with LOS as the outcome of interest and patient and surgical variables as covariates. RESULTS A total of 11 897 patients were analyzed. Among those discharged home, the regression analysis demonstrated significantly higher odds of longer LOS for patients undergoing surgery on Friday as compared to Monday ( P < .001). Among those discharged to a facility, there were significantly higher odds of longer LOS for patients undergoing surgery on Wednesday ( P < .001), Thursday ( P < .001), and Friday ( P = .002) as compared to Monday. CONCLUSION The findings of this study suggest that lumbar patients undergoing fusions and those discharged to a facility have longer LOS when surgery is later in the week. Scheduling these patients for surgery earlier in the week and ensuring adequate resources for patient disposition on weekends may lead to LOS reduction and cost savings for hospitals, payers, and patients alike.