Citations

Abstract Purpose: Pathologic fractures could be prevented if reliable methods of fracture risk assessment were available. A multicenter prospective study was conducted to identify significant predictors of physicians' treatment plan for skeletal metastasis based on clinical fracture risk assessments and the proposed CT-based Rigidity Analysis (CTRA). Experimental Design: Orthopedic oncologists selected a treatment plan for 124 patients with 149 metastatic lesions based on the Mirels method. Then, CTRA was performed, and the results were provided to the physicians, who were asked to reassess their treatment plan. The pre- and post-CTRA treatment plans were compared to identify cases in which the treatment plan was changed based on the CTRA report. Patients were followed for a 4-month period to establish the incidence of pathologic fractures. Results: Pain, lesion type, and lesion size were significant predictors of the pre-CTRA plan. After providing the CTRA results, physicians changed their plan for 36 patients. CTRA results, pain, and primary source of metastasis were significant predictors of the post-CTRA plan. Follow-up of patients who did not undergo fixation resulted in 7 fractures; CTRA predicted these fractures with 100% sensitivity and 90% specificity, whereas the Mirels method was 71% sensitive and 50% specific. Conclusions: Lesion type and size and pain level influenced the physicians' plans for the management of metastatic lesions. Physicians' treatment plans and fracture risk predictions were significantly influenced by the availability of CTRA results. Due to its high sensitivity and specificity, CTRA could potentially be used as a screening method for pathologic fractures. Clin Cancer Res; 21(11); 2514–9. ©2015 AACR.

BACKGROUND Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion‐related acute lung injury (TRALI), transfusion‐associated circulatory overload (TACO), and possible TRALI. STUDY DESIGN AND METHODS In a nested case‐control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147). Cytokines measured included granulocyte‐macrophage–colony‐stimulating factor, interleukin (IL)‐6, IL‐8, IL‐10, and tumor necrosis factor‐α. Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical predictors and laboratory markers in differentiating TACO, TRALI, and possible TRALI. RESULTS Before and after transfusion, IL‐6 and IL‐8 were elevated in patients with TRALI and possible TRALI relative to controls, and IL‐10 was elevated in patients with TACO and possible TRALI relative to that of TRALI and controls. For all pulmonary transfusion reactions, the combination of clinical variables and cytokine measurements displayed optimal diagnostic performance, and the model comparing TACO and TRALI correctly classified 92% of cases relative to expert panel diagnoses. CONCLUSIONS Before transfusion, there is evidence of systemic inflammation in patients who develop TRALI and possible TRALI but not TACO. A predictive model incorporating readily available clinical and cytokine data effectively differentiated transfusion‐related respiratory complications such as TRALI and TACO.

Abstract Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3′ untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P < 2.3 × 10−5) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. Cancer Discov; 5(4); 368–79. ©2015 AACR. See related commentary by Yousef, p. 351 This article is highlighted in the In This Issue feature, p. 333

SummarySixty‐four transplant‐eligible patients with newly diagnosed multiple myeloma (NDMM) received carfilzomib (days 1, 2, 8, 9, 15, 16), 300 mg/m2 cyclophosphamide (days 1, 8, 15), 100 mg thalidomide (days 1–28) and 40 mg dexamethasone (days 1, 8, 15, 22) in 28‐day cycles (CYKLONE regimen). Carfilzomib was dose‐escalated to 15/20, 20/27, 20/36 and 20/45 mg/m2 to determine the maximum tolerated dose (MTD), which was 20/36 mg/m2. Regardless of attribution, common Grade 3 or higher adverse events were lymphopenia (38%), neutropenia (23%) and anaemia (20%). All peripheral neuropathy (31%) was Grade 1 and considered most likely to be thalidomide‐related. Common cardiac or pulmonary events of any grade in ≥5% of patients included dyspnoea (20%) and cough (6%). Overall (N = 64), 91% of patients achieved a best response of partial response or better across all cycles of treatment, including five patients with complete responses. At the MTD (n = 29), 59% of patients achieved a very good partial response or better after four cycles (primary end point). Stem cell collection was successful in all patients in whom it was attempted (n = 42). Progression‐free survival and overall survival at 24 months was 76% and 96%, respectively (median follow‐up of 17·5 months). CYKLONE appears highly efficacious in NDMM patients, with manageable toxicities.

Objective: This study examines characteristics of individuals with bipolar disorder who sought psychotherapy versus those who did not. Methods: Bipolar CHOICE was an 11-site comparative effectiveness study of lithium versus quetiapine in symptomatic outpatients ( N = 482) with bipolar disorder. At baseline, participants’ psychotherapy use within the past 3 months, mood, functioning, and overall health were assessed. Logistic regressions were used to test whether psychotherapy users and non-users differed on various demographic and clinical variables at baseline. Mixed-effects regression was used to determine whether psychotherapy groups differed on response to treatment over the 6-month study. Kaplan-Meier plots and log-rank tests were employed to test whether there were any differences in time to recovery (CGI-BP ≤ 2 for at least 8 weeks) between the groups. Results: Thirty one percent of participants reported using psychotherapy services. Psychotherapy users reported greater medication side effect burden than non-users and were more likely to have moderate to high suicide risk and at least one anxiety disorder. Participants not utilizing medications or psychotherapy had greater mania symptom severity, were younger, and less educated than medication only users. Medication only users were more likely to be married than the other participants. Conclusions: These data suggest that a minority of individuals with bipolar disorder attend psychotherapy services, and those that do have greater illness burden.

BackgroundDetailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy.Study Design and MethodsTen US hospitals collected detailed medical information from the electronic health records for 1 year (2010‐2011) for all adult patients transfused with plasma.ResultsA total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2‐4; range 1‐72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5‐12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%‐75% interquartile range, 1.6‐2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4‐2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%).ConclusionThis large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used.