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OBJECTIVE Primary spinal osteosarcomas are rare and aggressive neoplasms. Poor outcomes can occur, as obtaining marginal margins is technically demanding; further Enneking-appropriate en bloc resection can have significant morbidity. The goal of this study is to identify prognostic variables for local recurrence and mortality in surgically treated patients diagnosed with a primary osteosarcoma of the spine. METHODS A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by AOSpine Knowledge Forum Tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified in 2 cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI), as defined by pathology margin matching Enneking-recommended surgical margins. Prognostic variables were analyzed in reference to local recurrence and survival. RESULTS Between 1987 and 2012, 58 patients (32 female patients) underwent surgical treatment for primary spinal osteosarcoma. Patients were followed for a mean period of 3.5 ± 3.5 years (range 0.5 days to 14.3 years). The median survival for the entire cohort was 6.7 years postoperative. Twenty-four (41%) patients died, and 17 (30%) patients suffered a local recurrence, 10 (59%) of whom died. Twenty-nine (53%) patients underwent EA resection while 26 (47%) patients underwent EI resection with a postoperative median survival of 6.8 and 3.7 years, respectively (p = 0.048). EI patients had a higher rate of local recurrence than EA patients (p = 0.001). Patient age, previous surgery, biopsy type, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. CONCLUSIONS Osteosarcoma of the spine presents a significant challenge, and most patients die in spite of aggressive surgery. There is a significant decrease in recurrence and an increase in survival with en bloc resection (EA) when compared with intralesional resection (EI). The effect of adjuvant and neoadjuvant chemotherapeutics, as well as method of biopsy, requires further exploration.

ABSTRACT The health care-associated pneumonia (HCAP) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. We aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of HCAP criteria. A derivation cohort of 200 microbiologically confirmed pneumonia cases in 2011 and 2012 was identified retrospectively. Risk factors for pneumonia due to drug-resistant pathogens were evaluated by logistic regression, and a novel prediction score (the drug resistance in pneumonia [DRIP] score) was derived. The score was then validated in a prospective, observational cohort of 200 microbiologically confirmed cases of pneumonia at four U.S. centers in 2013 and 2014. The DRIP score (area under the receiver operator curve [AUROC], 0.88 [95% confidence interval {CI}, 0.82 to 0.93]) performed significantly better ( P = 0.02) than the HCAP criteria (AUROC, 0.72 [95% CI, 0.64 to 0.79]). At a threshold of ≥4 points, the DRIP score demonstrated a sensitivity of 0.82 (95% CI, 0.67 to 0.88), a specificity of 0.81 (95% CI, 0.73 to 0.87), a positive predictive value (PPV) of 0.68 (95% CI, 0.56 to 0.78), and a negative predictive value (NPV) of 0.90 (95% CI, 0.81 to 0.93). By comparison, the performance of HCAP criteria was less favorable: sensitivity was 0.79 (95% CI, 0.67 to 0.88), specificity was 0.65 (95% CI, 0.56 to 0.73), PPV was 0.53 (95% CI, 0.42 to 0.63), and NPV was 0.86 (95% CI, 0.77 to 0.92). The overall accuracy of the HCAP criteria was 69.5% (95% CI, 62.5 to 75.7%), whereas that of the DRIP score was 81.5% (95% CI, 74.2 to 85.6%) ( P = 0.005). Unnecessary extended-spectrum antibiotics were recommended 46% less frequently by applying the DRIP score (25/200, 12.5%) than by use of HCAP criteria (47/200, 23.5%) ( P = 0.004), without increasing the rate at which inadequate treatment recommendations were made. The DRIP score was more predictive of the risk of pneumonia due to drug-resistant pathogens than HCAP criteria and may have the potential to decrease antibiotic overutilization in patients with pneumonia. Validation in larger cohorts of patients with pneumonia due to all causes is necessary.

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE‐PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE‐PGx data release includes sequence‐derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation‐Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

SummaryThe Wood's lamp aids in the diagnosis of multiple infectious, inflammatory and neoplastic dermatologic conditions. Although the Wood's lamp has many applications, which have improved both the diagnosis and management of disease, the man credited for its invention is relatively unknown in medicine. Robert Williams Wood, a prominent physicist of the early 20th century, is credited for the invention of the Wood's lamp. Wood was the father of infrared and ultraviolet photography and made significant contributions to other areas in optics and spectroscopy. Wood's work encompassed the formative years of American Physics; he published over 200 original papers over his lifetime. A few years after the invention of the Wood's lamp for ultraviolet photography, physicians in Europe adopted the Wood's lamp for dermatologic applications. Wood's lamp remains popular in clinics globally, given its ease of use and ability to improve diagnostic precision.

OBJECT A chordoma is an indolent primary spinal tumor that has devastating effects on the patient's life. These lesions are chemoresistant, resistant to conventional radiotherapy, and moderately sensitive to proton therapy; however, en bloc resection remains the preferred treatment for optimizing patient outcomes. While multiple small and largely retrospective studies have investigated the outcomes following en bloc resection of chordomas in the sacrum, there have been few large-scale studies on patients with chordomas of the mobile spine. The goal of this study was to review the outcomes of surgically treated patients with mobile spine chordomas at multiple international centers with respect to local recurrence and survival. This multiinstitutional retrospective study collected data between 1988 and 2012 about prognosis-predicting factors, including various clinical characteristics and surgical techniques for mobile spine chordoma. Tumors were classified according to the Enneking principles and analyzed in 2 treatment cohorts: Enneking-appropriate (EA) and Enneking-inappropriate (EI) cohorts. Patients were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation; otherwise, they were categorized as EI. METHODS Descriptive statistics were used to summarize the data (Student t-test, chi-square, and Fisher exact tests). Recurrence and survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazard modeling. RESULTS A total of 166 patients (55 female and 111 male patients) with mobile spine chordoma were included. The median patient follow-up was 2.6 years (range 1 day to 22.5 years). Fifty-eight (41%) patients were EA and 84 (59%) patients were EI. The type of biopsy (p < 0.001), spinal location (p = 0.018), and if the patient received adjuvant therapy (p < 0.001) were significantly different between the 2 cohorts. Overall, 58 (35%) patients developed local recurrence and 57 (34%) patients died. Median survival was 7.0 years postoperative: 8.4 years postoperative for EA patients and 6.4 years postoperative for EI patients (p = 0.023). The multivariate analysis showed that the EI cohort was significantly associated with an increased risk of local recurrence in comparison with the EA cohort (HR 7.02; 95% CI 2.96–16.6; p < 0.001), although no significant difference in survival was observed. CONCLUSIONS EA resection plays a major role in decreasing the risk for local recurrence in patients with chordoma of the mobile spine.

Autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders, is characterized by kidney failure caused by bilateral renal cyst growth. MicroRNAs (miRs) have been implicated in numerous diseases, but the role of these noncoding RNAs in ADPKD pathogenesis is still poorly defined. Here, we investigated the role of miR-21, an oncogenic miR, in kidney cyst growth. We found that transcriptional activation of miR-21 is a common feature of murine PKD. Furthermore, compared with renal tubules from kidney samples of normal controls, cysts in kidney samples from patients with ADPKD had increased levels of miR-21. cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and promoted miR-21 expression in cystic kidneys of mice. Genetic deletion of miR-21 attenuated cyst burden, reduced kidney injury, and improved survival of an orthologous model of ADPKD. RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likely through direct repression of its target gene programmed cell death 4 . Thus, miR-21 functions downstream of the cAMP pathway and promotes disease progression in experimental PKD. Our results suggest that inhibiting miR-21 is a potential new therapeutic approach to slow cyst growth in PKD.

Background: Limited information exists on the clinical use of a synthetic osteochondral scaffold plug for cartilage restoration in the knee. Purpose/Hypothesis: The purpose of this study was to compare the early magnetic resonance imaging (MRI) appearance, including quantitative T2 values, between cartilage defects treated with a scaffold versus a scaffold with platelet-rich plasma (PRP) or bone marrow aspirate concentrate (BMAC). The hypothesis was that the addition of PRP or BMAC would result in an improved cartilage appearance. Study Design: Cohort study; Level of evidence, 3. Methods: Forty-six patients with full-thickness cartilage defects of the femur were surgically treated with a control scaffold (n = 11), scaffold with PRP (n = 23), or scaffold with BMAC (n = 12) and were followed prospectively. Patients underwent MRI with a qualitative assessment and quantitative T2 mapping at 12 months after surgery. An image assessment was performed retrospectively by a blinded musculoskeletal radiologist. The cartilage phase was measured by cartilage fill and quantitative T2 values on MRI. A comparison between groups after cartilage repair was performed. Results: The control scaffold group consisted of 8 male and 3 female patients (mean age, 38 years; mean body mass index [BMI], 25 kg/m 2 ), the PRP group had 15 male and 8 female patients (mean age, 39 years; mean BMI, 26 kg/m 2 ), and the BMAC group consisted of 8 male and 4 female patients (mean age, 36 years; mean BMI, 26 kg/m 2 ). The PRP-treated ( P = .002) and BMAC-treated ( P = .03) scaffolds had superior cartilage fill compared with the control group. With quantitative methods, the PRP group demonstrated a mean T2 value (49.1 ms) that was similar to that of the control scaffold group (42.7 ms; P = .07), but the BMAC group demonstrated a mean T2 value (60.5 ms) closer to that of superficial hyaline cartilage ( P = .01). The stratification of T2 values between the deep and superficial zones was not observed in any of the groups. Conclusion: In this comparative study, patients treated with scaffold implantation augmented with BMAC had improved cartilage maturation with greater fill and mean T2 values closer to that of superficial native hyaline cartilage at 12 months. Further work will determine if this translates into improved clinical outcomes.

Abstract Purpose: Preclinical studies suggest that SNPs in the Fc gamma receptor (FCGR) genes influence response to rituximab, but the clinical relevance of this is uncertain. Experimental Design: We prospectively obtained specimens for genotyping in the rituximab extended schedule or re-treatment trial (RESORT) study, in which 408 previously untreated, low tumor burden follicular lymphoma (FL) patients were treated with single agent rituximab. Patients received rituximab in 4 weekly doses and responders were randomized to rituximab re-treatment (RR) upon progression versus maintenance rituximab (MR). SNP genotyping was performed in 321 consenting patients. Results: Response rates to initial therapy and response duration were correlated with the FCGR3A SNP at position 158 (rs396991) and the FCGR2A SNP at position 131 (rs1801274). The response rate to initial rituximab was 71%. No FCGR genotypes or grouping of genotypes were predictive of initial response. A total of 289 patients were randomized to RR (n = 143) or to MR (n = 146). With a median follow-up of 5.5 years, the 3-year response duration in the RR arm and the MR arm was 50% and 78%, respectively. Genotyping was available in 235 of 289 randomized patients. In patients receiving RR (n = 115) or MR (n = 120), response duration was not associated with any FCGR genotypes or genotype combinations. Conclusions: Based on this analysis of treatment-naïve, low tumor burden FL, we conclude that the FCGR3A and FCGR2A SNPs do not confer differential responsiveness to rituximab. Clin Cancer Res; 22(4); 821–6. ©2015 AACR. See related commentary by Cartron et al., p. 787