Citations

Abstract Genome-wide association studies (GWAS) conducted among populations of European ancestry (EA) have identified 23 common single nucleotide polymorphisms (SNPs) associated with multiple myeloma (MM) risk. We hypothesize that the combination of these SNPs in a polygenic risk score (PRS) is likely to be a strong risk factor for MM. However, it is unclear whether the genetic variation associated with MM susceptibility also predisposes to monoclonal gammopathy of undetermined significance (MGUS). Thus, we calculated a PRS and evaluated the association with risk of MM and its precursor, MGUS. We pooled genotype data for 2434 MM and 3446 controls from ten MM GWAS of individuals of EA within the Interlymph Consortium, for 23 MM risk SNPs identified by prior GWAS. An additional 754 MGUS cases were ascertained from Mayo Clinic and MD Anderson clinical practices. To calculate the PRS, we used the risk estimates corresponding to the 23 SNP associations from the largest published MM GWAS. The log of the odds ratio (OR) for each SNP was multiplied by the respective number of risk alleles and summed to generate a PRS for each individual. The PRS was examined continuously, per one standard deviation (SD), and as quintiles, based on the PRS distribution in the controls. Associations of PRS with MM and MGUS risk were examined separately, using multivariable logistic regression assuming an additive model to assess ORs and 95% confidence intervals adjusted for age, sex, and site. We also evaluated age and sex stratified models. The distribution of sex within MM cases, MGUS cases and controls were each ~60% male and ~40% female. The median age was 61, 66, and 66 years for MM cases, MGUS cases and controls, respectively. PRS ranged from 1.52-4.91, with a median PRS of 3.21 for MM cases, 3.19 for MGUS cases, and 3.05 for controls. PRS was significantly associated with MM risk when assessed continuously (OR=1.19 per SD, p=2.2x10-16) and categorically; compared with the middle quintile (Q3), individuals in the highest quintile (Q5) had a 66% increased MM risk (OR=1.66, p=2.3x10-9) and those in the lowest quintile (Q1) had a 38% decreased MM risk (OR=0.62, p=1.3x10-6). PRS was also significantly associated with MGUS risk (OR=1.19 per SD, p=1.7x10-11); individuals with the highest PRS (Q5) had a 77% increased risk (OR=1.77, p=4.0x10-4) and those with lowest PRS (Q1) had 30% decreased risk (OR=0.70, p=0.04), compared with Q3. When stratified by age and sex, similar associations and trends were found. Using an independent sample of MM / MGUS cases and controls, we showed that a PRS constructed from 23 common genetic variants for MM risk is associated with risk of both MM and MGUS, regardless of age or sex. A future direction of this work is testing associations with PRS and clinical characteristics of the MM cases, as well as differences between MGUS cases that progress and those that do not. Our results suggest that common genetic variation may predispose to MGUS as the precursor to MM. Citation Format: Alyssa I. Clay-Gilmour, Michelle A. Hildebrandt, Nicola J. Camp, Elad Ziv, Elizabeth E. Brown, Jonathan N. Hofmann, John J. Spinelli, Graham G. Giles, Parveen Bhatti, Wendy Cozen, Xifeng Wu, Dennis P. Robinson, Aaron D. Norman, Jason P. Sinnwell, Shaji K. Kumar, S Vincent Rajkumar, Susan L. Slager, Celine M. Vachon. Associations between a polygenic risk score and risk of multiple myeloma and its precursor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2686.

Abstract Proliferative glomerulonephritis (GN) with monoclonal immunoglobulin deposits (PGNMIDs) is a recently described entity among the spectrum of monoclonal gammopathy of renal significance (MGRS). The disease is renal limited and manifests with chronic glomerular disease, altered renal function and albuminuria, sometimes in the nephrotic range. Acute nephritic syndrome is rare. PGNMID occurs mostly in the sixth decade, but it may affect young adults. Histologically, PGNMID is characterized predominantly by membranoproliferative GN and less frequently by diffuse endocapillary GN, mesangioproliferative GN or atypical membranous GN. Immunofluorescence and electron microscopic studies are the cornerstone of diagnosis, showing granular deposits involving glomeruli only, and composed of monotypic immunoglobulin G (IgG), with a single heavy chain subclass (most commonly IgG3) and light chain (LC) restriction (usually κ), admixed with complement deposits. PGNMID variants with monotypic LC-only, IgA or IgM deposits are uncommon. Ultrastructurally, deposits are amorphous with predominant subendothelial and mesangial distribution. PGNMID should be distinguished from type 1 cryoglobulinemic GN and immunotactoid GN, which share some common pathological features. Contrary to other MGRS lesions, the rate of detection of the nephrotoxic monoclonal Ig in the serum or urine, and of an abnormal bone marrow B-cell clone, is only ∼30%. Renal prognosis is poor, with progression to end-stage renal disease in 25% of patients within 30 months and frequent early recurrence on the renal allograft. The pathophysiology of PGNMID is unclear and its treatment remains challenging. However, recent studies indicate that clone-targeted chemotherapy may significantly improve renal outcomes, opening future perspectives for the management of this rare disease.

Background: Hamstring strains are the most common injury for professional baseball players and can result in significant time on the disabled list. To date, no study has reported the current trends in hamstring strains in professional baseball. Hypothesis: Professional baseball players would have an increased incidence of hamstring strains from 2011 through 2016. Study Design: Descriptive epidemiology study. Methods: Injury data were prospectively collected from 2011 through 2016 for every Major League Baseball (MLB) and Minor League Baseball (MiLB) team and was recorded in the MLB Health and Injury Tracking System. Data collected for this study included date of injury, activity during injury, time lost, primary injury or reinjury status, and imaging findings as well as player demographic information related to level of play, age, and position for all hamstring injury events. Injury rates were reported as hamstring injuries per number of games. Results: From 2011 to 2016, there were 2633 hamstring strains in professional baseball players. The rate of hamstring strains increased in MLB from a low of 1 injury every 39 games in 2011 to a high of 1 injury every 30 games in 2016. In MiLB, there were 2192 hamstring strains, with 1 injury every 35 games in 2011 compared with 1 injury every 30 games in 2016. The majority of injuries occurred in the infielder positions (37.5%) and resulted from base running (>50%), most commonly from home to first base. The most common hamstring injury was a grade 2 injury to the distal biceps femoris. The mean time missed after a hamstring injury was 14.5 days. Grade 3 and grade 2 hamstring strains resulted in significantly more days missed compared with grade 1 injuries ( P = .005 and P = .002, respectively). The rate of recurrent hamstring injuries was 16.3% for MLB and 14.2% for MiLB. Recurrent hamstring injuries resulted in more time lost than primary injuries (mean, 16.4 vs 14.5 days, respectively; P = .02). A total of 42 injuries were treated with platelet-rich plasma, and 19 were treated with surgery. The number of injuries treated with platelet-rich plasma increased in successive years. Conclusion: The rate of hamstring strains in professional baseball players has increased over the past 6 years and has resulted in a significant loss of playing time. Study results indicated that these injuries are affected by injury characteristics, position played, running to first base, seasonal timing, and history of hamstring injuries.

Background Preliminary clinical studies on the safety and efficacy of the pipeline embolization device (PED) for the treatment of small/medium aneurysms have demonstrated high occlusion rates with low complications. Objective To evaluate the safety and effectiveness of the PED for treatment of wide necked small and medium intracranial aneurysms. Methods PREMIER is a prospective, multicenter, single arm trial. Patients were treated with the PED for unruptured wide necked aneurysms, measuring ≤12 mm along the internal carotid artery or vertebral artery, between July 2014 and November 2015. At 1 year post-procedure, the primary effectiveness endpoint was complete occlusion (Raymond grade 1) without major parent vessel stenosis (≤50%) or retreatment, and the primary safety endpoint was major stroke in the territory supplied by the treated artery or neurologic death. Results A total of 141 patients were treated with PEDs (mean age 54.6±11.3 years, 87.9% (124/141) women). Mean aneurysm size was 5.0±1.92 mm, and 84.4% (119/141) measured <7 mm. PED placement was successful in 99.3% (140/141) of patients. Mean number of PEDs implanted per patient was 1.1±0.26; a single PED was used in 92.9% (131/141) of patients. At 1 year, 97.9% (138/141) of patients underwent follow-up angiography with 76.8% (106/138) of patients having met the study’s primary effectiveness endpoint. The combined major morbidity and mortality rate was 2.1% (3/140). Conclusions Treatment of wide necked small/medium aneurysms with the PED results in high rates of complete occlusion without significant parent vessel stenosis and low rates of permanent neurologic complications. Trial registration NCT02186561 .

Summary Improvement in survival in Light chain (AL) amyloidosis has been seen over recent decades, enabling more patients to achieve long‐term survival. Patients with AL amyloidosis who survived ≥10 years from time of diagnosis ( n = 186) were the subject of this study. Ten‐year survivors represented 22% of the total population. These patients were characterized by favourable patient, organ and plasma cell features. Of note, trisomies were less common among 10‐year survivors compared to those who did not survive to 10 years. All‐time best haematological response was complete response in 67%, very good partial response in 30%, partial response in 2% and no response in 1%, with 11% having received a consolidative strategy for inadequate response to first line therapy. The overall organ response rate to first‐line therapy was 76%, which increased to 86% when considering subsequent line(s) of therapy. Forty‐seven percent of the 10‐year survivors did not require a second‐line therapy. The median treatment‐free survival (TFS) among the 10‐year survivors was 10·5 years (interquartile range 7·4‐12·2). On multivariate analysis independent predictors for TFS were the achievement of complete haematological response and lack of cardiac involvement. Long‐term survivors are increasingly seen in AL amyloidosis and present distinct patient, organ and clonal disease features.

Pseudoaneurysm (PSA) formation is a potential complication of breast biopsies. Ultrasound is the most common imaging modality used for evaluation and treatment of a PSA. Color Doppler images show a cystic structure with swirling flow inside in a “to‐and‐fro” pattern. Treatment options for PSA include observation, ultrasound‐guided focused compression, thrombin injection, open surgical repair, and percutaneous embolization. The risks and benefits of these treatment options will be discussed in the following cases.

BackgroundThere exist insufficient data characterizing patients with multiple myeloma (MM) who experienced prolonged survival. A population‐based analysis of long‐term survivors was conducted to investigate the roles of sociodemographic factors and upfront stem cell transplantation (SCT).MethodsThe National Cancer Data Base is a US cancer database of approximately 34 million patients from >1500 cancer centers. Patients with MM were identified using the International Classification of Diseases for Oncology (ICD‐O) code 9732 from January 2004 to December 2006 and were divided into 4 groups based on overall survival (OS). Sociodemographic characteristics, treatment facility, and use of SCT were recorded. The univariate and multivariate analyses were performed using multiple logistic regression and Pearson chi‐square tests.ResultsA total of 26,986 patients with MM were identified. The median OS was 2.74 years. The majority of patients were male (54%), white (77%), insured (93%) and otherwise healthy (78%), lived in a metropolitan area (82%), were of high income (66%) and educational (58%) levels, and received treatment at nonacademic facilities (63%). Upfront SCT was used in 10% of patients. One in 6 patients (16%) were long‐term survivors (group 4). When comparing group 4 (OS of ≥8.22 years) with the other groups (OS of <8.22 years), young age, female sex, high income and educational levels, residence in a rural area, insured status, no comorbidity, receipt of upfront SCT, and treatment at high‐volume facilities were associated with long‐term survival.ConclusionsKey differences in sociodemographic characteristics, patient volume at treatment facilities, and upfront SCT were associated with long‐term survival. Improvements in health care access and health literacy, upfront SCT, and treatment at high‐volume facilities might prolong patient survival.

Abstract The high-risk abnormality del(17p) can be detected by fluorescence in situ hybridization on malignant plasma cells (PCs) and has an adverse prognostic impact in patients with multiple myeloma (MM). Patients with del(17p) have reduced overall survival (OS). Patients who acquire del(17p) later during the disease course are not well described. The disease characteristics at diagnosis predicting for acquired del(17p) and its overall impact on patient survival is not known. We compared 76 patients with MM who were negative for del(17p) at diagnosis and acquired it later with 152 control MM patients who did not acquire del(17p) at a comparable time point. Patients acquired del(17p) at a median of 35.6 months (range, 4.6-116.1 months) from diagnosis of MM after a median of 2 lines of therapy (range, 1-10 lines of therapy). When compared with controls, patients with acquired del(17p) had shorter median progression-free survival (PFS) (30.1 vs 23.0 months; P = .032) and OS (106.1 vs 68.2 months; P &lt; .001) from diagnosis. After the detection of del(17p), the median PFS was 5.4 months and the median OS was 18.1 months. High lactate dehydrogenase level (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.11-12.24) and presence of t(4;14) (OR, 2.66; 95% CI, 1.09-6.48) or any high-risk translocation (OR, 2.23; 95% CI, 1.00-4.95) at diagnosis predicted acquisition of del(17p). High PC proliferative rate predicted shorter OS from detection of del(17p) (hazard ratio, 2.28; 95% CI, 1.31-3.96; P = .004). Our study shows that acquisition of del(17p) is an important molecular event associated with reduction in OS in MM. Certain baseline factors may predict acquisition of del(17p). This needs validation in prospective data sets.