Citations

OBJECTIVEQuality and outcomes registry platforms lie at the center of many emerging evidence-driven reform models. Specifically, clinical registry data are progressively informing health care decision-making. In this analysis, the authors used data from a national prospective outcomes registry (the Quality Outcomes Database) to develop a predictive model for 12-month postoperative pain, disability, and quality of life (QOL) in patients undergoing elective lumbar spine surgery.METHODSIncluded in this analysis were 7618 patients who had completed 12 months of follow-up. The authors prospectively assessed baseline and 12-month patient-reported outcomes (PROs) via telephone interviews. The PROs assessed were those ascertained using the Oswestry Disability Index (ODI), EQ-5D, and numeric rating scale (NRS) for back pain (BP) and leg pain (LP). Variables analyzed for the predictive model included age, gender, body mass index, race, education level, history of prior surgery, smoking status, comorbid conditions, American Society of Anesthesiologists (ASA) score, symptom duration, indication for surgery, number of levels surgically treated, history of fusion surgery, surgical approach, receipt of workers’ compensation, liability insurance, insurance status, and ambulatory ability. To create a predictive model, each 12-month PRO was treated as an ordinal dependent variable and a separate proportional-odds ordinal logistic regression model was fitted for each PRO.RESULTSThere was a significant improvement in all PROs (p < 0.0001) at 12 months following lumbar spine surgery. The most important predictors of overall disability, QOL, and pain outcomes following lumbar spine surgery were employment status, baseline NRS-BP scores, psychological distress, baseline ODI scores, level of education, workers’ compensation status, symptom duration, race, baseline NRS-LP scores, ASA score, age, predominant symptom, smoking status, and insurance status. The prediction discrimination of the 4 separate novel predictive models was good, with a c-index of 0.69 for ODI, 0.69 for EQ-5D, 0.67 for NRS-BP, and 0.64 for NRS-LP (i.e., good concordance between predicted outcomes and observed outcomes).CONCLUSIONSThis study found that preoperative patient-specific factors derived from a prospective national outcomes registry significantly influence PRO measures of treatment effectiveness at 12 months after lumbar surgery. Novel predictive models constructed with these data hold the potential to improve surgical effectiveness and the overall value of spine surgery by optimizing patient selection and identifying important modifiable factors before a surgery even takes place. Furthermore, these models can advance patient-focused care when used as shared decision-making tools during preoperative patient counseling.

Abstract Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P &lt; 3.5 × 10−5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420–4. ©2016 AACR.

AbstractBackgroundA fundamental obstacle to using retroviral‐mediated gene transfer (GT) to treat human diseases is the relatively low transduction levels that have been achieved in clinically relevant human cells. We previously showed that performing GT in utero overcomes this obstacle and results in significant levels of transduction within multiple fetal organs, with different tissues exhibiting optimal transduction at different developmental stages. We undertook the present study aiming to elucidate the mechanism for this age‐dependent transduction, testing the two factors that we hypothesized could be responsible: (i) the proliferative status of the tissue at the time of GT and (ii) the expression level of the amphotropic PiT‐2 receptor.MethodsImmunofluorescence was performed on tissues from sheep of varying developmental stages to assess the proliferative status of the predominant cells within each organ as a function of age. After developing an enzyme‐linked immunosorbent assay (ELISA) and a quantitative reverse transcription chain reaction (qRT‐PCR) assay, we then quantified PiT‐2 expression at the protein and mRNA levels, respectively.ResultsThe results obtained indicate that the proliferative status of organs at the time of fetal GT is not the major determinant governing transduction efficiency. By contrast, our ELISA and qRT‐PCR analyses demonstrated that PiT‐2 mRNA and protein levels vary with gestational age, correlating with the observed differences in transduction efficiency.ConclusionsThe findings of the present study explain the age‐related differences that we previously observed in transduction efficiency after in utero GT. They also suggest it may be possible to achieve relatively selective GT to specific tissues by performing in utero GT when levels of PiT‐2 are maximal in the desired target organ. Copyright © 2012 John Wiley & Sons, Ltd.

Abstract ST6Gal-1 is a participant in regulating not only Th1 but also Th2 responses; ST6Gal-1 deficiency can lead to the development of more severe allergic inflammation with excessive eosinophil production. Cumulative evidence indicates that the sialyltransferase ST6Gal-1 and the sialyl-glycans, which it constructs, are functionally pleiotropic. Expression of the ST6Gal-1 gene is mediated by six distinct promoter/regulatory regions, and we hypothesized that these promoters may be used differentially to produce ST6Gal-1 for different biologic purposes. To examine this hypothesis, we compared a mouse with a complete deficiency in ST6Gal-1 (Siat1 null) with another mouse that we have created previously with a disruption only in the P1 promoter (Siat1ΔP1). We noted previously greater neutrophilic inflammation associated with ST6Gal-1 deficiency. Here, we report that ST6Gal-1-deficient mice also have significantly elevated eosinophilic responses. Upon i.p. thioglycollate elicitation, eosinophils accounted for over 20% of the total peritoneal inflammatory cell pool in ST6Gal-1-deficient animals, which was threefold greater than in corresponding wild-type animals. A principal feature of allergic respiratory inflammation is pulmonary eosinophilia, we evaluated the role of ST6Gal-1 in allergic lung inflammation. Using OVA and ABPA experimental models of allergic airways, we showed that ST6Gal-1 deficiency led to greater airway inflammation characterized by excessive airway eosinophilia. The severity of airway inflammation was similar between Siat1ΔP1 and Siat1 null mice, indicating a role for P1-generated ST6Gal-1 in regulating eosinophilic inflammation. Colony-forming assays suggested greater IL-5-dependent eosinophil progenitor numbers in the marrow of ST6Gal-1-deficient animals. Moreover, allergen provocation of wild-type mice led to a significant reduction in P1-mediated ST6Gal-1 mRNA and accompanied decline in circulatory ST6Gal-1 levels. Taken together, the data implicate ST6Gal-1 as a participant in regulating not only Th1 but also Th2 responses, and ST6Gal-1 deficiency can lead to the development of more severe allergic inflammation with excessive eosinophil production.

Object Stereotactic radiosurgery (SRS) has proven to be a safe and effective treatment for many patients with intracranial meningiomas. Nevertheless, the morbidity associated with radiosurgery of larger meningiomas is poorly understood. Methods The authors performed a retrospective review of 116 patients who underwent SRS for meningiomas (WHO Grade I) > 10 cm3 between 1990 and 2007, with a minimum follow-up of 12 months. Patients with atypical or malignant meningiomas and those who received prior radiotherapy were excluded. The average tumor volume was 17.5 cm3 (range 10.1–48.6 cm3); the average tumor margin dose was 15.1 Gy (range 12–18 Gy); and the mean follow-up duration was 70.1 months (range 12–199 months). Results Tumor control was 99% at 3 years and 92% at 7 years after radiosurgery. Thirty complications after radiosurgery were noted in 27 patients (23%), including 7 cases of seizures, 6 cases of hemiparesis, 5 cases of trigeminal injury, 4 cases of headaches, 3 cases of diplopia, 2 cases each of cerebral infarction and ataxia, and 1 case of hearing loss. Patients with supratentorial tumors experienced a higher complication rate compared with patients with skull base tumors (44% compared with 18%) (hazard ratio 2.9, 95% CI 1.3–6.7, p = 0.01). Conclusions The morbidity associated with SRS for patients with benign meningiomas > 10 cm3 is greater for supratentorial tumors compared with skull base tumors. Whereas radiosurgery is relatively safe for patients with large-volume skull base meningiomas, resection should remain the primary disease management for the majority of patients with large-volume supratentorial meningiomas.