Citations

Over the past decade, a number of changes have occurred in the diagnostic evaluation, management, and long‐term follow‐up of patients with POEMS syndrome at our institution. This study included 291 patients with POEMS syndrome diagnosed at the Mayo Clinic between 1974 and 2014. Patients diagnosed after 2003 had more features of the syndrome identified at diagnosis and were more likely to receive an autologous transplant (49% versus 8%, P < 0.0001) and to have achieved a hematologic complete response (CR) to treatment (41% vs 25%, P < 0.0001). With 2273 person‐years of follow‐up, 10‐year overall survival (OS) was 62% (95% C.I., 56%, 67%). On multivariate analysis, the three factors associated with superior OS were younger age (RR 0.98 [0.96–1.00]), albumin greater‐than 3.2 g/dL (RR 0.5 [0.32–0.89]) and attainment of complete hematologic response (RR 0.4 [0.2, 0.9]). This study confirms the very good long‐term outcomes of patients with POEMS syndrome and identifies two new prognostic risk factors: albumin at diagnosis and attainment of complete hematologic response. Am. J. Hematol. 91:585–589, 2016. © 2016 Wiley Periodicals, Inc.

ABSTRACTPreservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA‐seq) and real‐time reverse transcription quantitative polymerase chain reaction (RT‐qPCR) to assess genome‐wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM‐related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950–1959, 2016.

A single monoclonal protein typically characterizes monoclonal gammopathies, but a small proportion may have more than one M protein identifiable. In the setting of symptomatic multiple myeloma (MM), the development of a new monoclonal protein following therapy is associated with better outcomes. As for the precursor conditions, monoclonal gammopathy undetermined significance (MGUS) and smoldering multiple myeloma (SMM), there is limited information on the impact of a second monoclonal protein on the disease course, including progression and response to treatment. The outcomes of patients with MGUS and SMM with more than one monoclonal protein, after identifying 539 patients with biclonal proteins on electrophoresis and/or immunofixation, were reported. About 22 of 393 patients with MGUS/biclonal gammopathy of undetermined significance (BGUS) progressed to SMM (6), MM (11), AL (3), or WM (2), and 5 of 16 patients with biclonal SMM progressed to MM. The rate of progression for BGUS was approximately 1% per year, which is similar to MGUS with one monoclonal protein. The median estimated time of progression of biclonal SMM was 2.6 years; similar to monoclonal SMM. For patients with biclonal MM, both M spikes responded to treatment and, upon relapse, the original dominant M protein remained dominant as the disease progressed. In conclusion, the presence of a second monoclonal protein does not appear to affect the progression of precursor states and suggests multiple monoclonal proteins do not clinically impact one another in the course of the disease. Am. J. Hematol. 91:473–475, 2016. © 2016 Wiley Periodicals, Inc.

Abstract Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). Methods: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). Results: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E−6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E−6; Pcorrected = 0.01). Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. Impact: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446–54. ©2016 AACR.

Complementary and alternative medicine (CAM) has gained acceptance throughout the industrialized world. The present study was performed to provide information about the use of CAM at Mayo Clinic, an academic medical center in Northern Midwest of the US. We retrospectively reviewed the electronic medical records of 2680 patients visiting the CAM program at Mayo Clinic, Rochester, between 1 July 2006 and 31 March 2011. Services provided included acupuncture, massage, integrative medical consultations and executive stress management training. Data including age, gender, race, diagnosis and the number of treatment/consultation sessions were collected to describe the use of CAM in our institute over the last several years. It was found that the mean (standard deviation) age of patient was 52.6 (15.5) years. Of those, 73.1% were female and 26.9% were male. Most patients were white. The number of patients referred to CAM increased significantly from 2007 to 2010. The three most common diagnostic categories were back pain (12.9%), psychological disorders (11.8%), and joint pain (9.6%). Back pain was the most common diagnosis for patients receiving acupuncture, and fibromyalgia was the most common for patients receiving massage therapy. Psychological disorders (i.e., stress) were the major diagnosis referred to both integrative medical consults and executive stress management training. These results suggest that the diseases related to pain and psychological disorders are the main fields of CAM use. It also shows the increasing trend of the use of CAM at an academic medical center in the US.