Citations

Abstract Purpose: Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in patients with newly diagnosed multiple myeloma. Experimental Design: This is a retrospective study including 1,342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, who had cytogenetic testing by FISH at diagnosis, including MYC testing using the break apart FISH probe (8q24.1). Results: A rearrangement involving MYC was found in 8% of patients and was associated with elevated β2-microglobulin, ≥50% bone marrow plasma cells, IgA multiple myeloma, and the cooccurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)-based or PI + IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared with patients without MYC rearrangement (5.3 vs. 8.0 years, P < 0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5; P = 0.007). Conclusions: MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in patients with newly diagnosed multiple myeloma.

This is the first sham-controlled study to investigate the effects of leg heat therapy (HT) on walking performance, vascular function, and quality of life in patients with peripheral artery disease (PAD). Adherence to HT was high, and the treatment was well tolerated. Our findings revealed that HT applied with water-circulating trousers evokes a clinically meaningful increase in perceived physical function and reduces the serum concentration of the potent vasoconstrictor endothelin-1 in patients with PAD.

Abstract Objective Image-guided breast biopsies are safe, efficient, and reliable. However, patients are often anxious about these procedures, particularly those who have never undergone a prior biopsy. Methods This prospective IRB-approved study surveyed 163 patients undergoing their first breast biopsy. Participants provided informed consent and completed a short written survey prior to and immediately after their procedure. Level of anxiety as well as anticipated and actual levels of pain prior to and following the procedure were assessed using a 0–10-point Likert scale. Correlation, bivariate, and regression analyses were performed. Results Regarding the biopsy experience, 133/163 (81.6%) of patients reported it as better than expected. Anxiety decreased significantly from a prebiopsy mean score of 5.52 to a postbiopsy mean score of 2.25 (P < 0.001). Average and greatest pain experienced during the procedure had mean scores of 2.03 and 2.77, respectively, both significantly lower compared to preprocedural expectation (mean 4.53) (P < 0.001). Lower pain scores were reported in US-guided procedures compared to stereotactic- and MRI-guided biopsies (P < 0.001). No significant differences in pain scores were seen in those undergoing single versus multiple biopsies, or when benign, elevated-risk, or malignant lesions were sampled. Positive correlations were seen with prebiopsy anxiety levels and procedural pain as well as with anticipated pain and actual procedural pain. Conclusion Image-guided biopsies are often better tolerated by patients than anticipated. We stress the benefit of conveying this information to patients prior to biopsy, as decreased anxiety correlates with lower levels of pain experienced during the procedure.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( p < 0.001), predominantly female ( p = 0.01) and had higher mean Charlson scores ( p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.

Abstract Central giant cell granuloma (CGCG) is a relatively uncommon benign bony lesion accounting for approximately 7% of all non-neoplastic lesions of the jaw. The clinical behavior of CGCG can vary from a slow-growing, painless lesion to fast-growing and locally destructive. When such a lesion involves the mandible, this can be quite debilitating for the patient, inhibiting oral intake and requiring an extensive resection and bone graft reconstruction. The authors present a case of effectively decreasing the surgical morbidity associated with a large and rapidly growing CGCG of the mandible in a pediatric patient. Neoadjuvant immunotherapy with denosumab (human monoclonal antibody) facilitated treatment of the tumor without the need for a large resection which would have otherwise necessitated a vascularized bony mandibular reconstruction. Consideration of neoadjuvant medical management of CGCG as the primary treatment is advocated.

AbstractWe previously demonstrated that cancer‐associated fibroblasts (CAFs) promoted the proliferation of gallbladder cancer (GBC) cells, but the mechanism is not clear. Neuropilin‐1 (NRP‐1) plays an important role in various malignancies as transmembrane glycoprotein. Our goal was to reveal the relationship between CAFs and NRP‐1 and their potential functions in GBC. In this study, we found NRP‐1 was overexpressed in GBC tissue, associated with poor survival and was up‐regulated by CAFs. The cytokine array cluster analysis revealed IL‐8 secreted by CAFs facilitated the up‐regulation of NRP‐1 in tumour cells. NRP‐1 knockdown suppressed tumour growth in vivo. Gene expression microarray analysis showed 581 differentially regulated genes under NRP‐1 knockdown conditions. Ingenuity pathway analysis demonstrated that NRP‐1 knockdown may inhibit tumour progression by affecting cell proliferation. We then confirmed that NRP‐1 knockdown in NOZ and GBC‐SD cells significantly inhibited cell proliferation. Additionally, the IL‐8 mediated MDM2 and CCNA2 expression were affected by NRP‐1 knockdown. Our findings suggested that NRP‐1 was up‐regulated by CAF‐secreted IL‐8, which subsequently promoted GBC cell proliferation, and these molecules may serve as useful prognostic biomarkers and therapeutic targets for GBC.

Abstract Aim Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches. Methods This is a multi‐institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan–Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence. Results Two‐hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% ( n = 115/180) of women remained recurrence free at median follow‐up of 14.6 months (IQR, 3–37). In unadjusted analysis, recurrence‐free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence. Conclusion This retrospective multi‐institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.

Key Points An incidental histologic diagnosis of DLBCL was identified during temporary interruption of ibrutinib treatment in patients with CLL. In contrast to an aggressive clinical course typical of Richter transformation, these patients responded to reinitiation of ibrutinib alone.

PurposeIn quantitative susceptibility mapping (QSM) using magnetic resonance imaging, image reconstruction methods usually aim at suppressing streaking artifacts. In this study, a streaking detection method is proposed for evaluating and optimizing quantitative susceptibility maps.MethodsNine healthy subjects participated in this study and underwent three‐dimensional multi‐echo gradient echo scans. Regularized iterative algorithm was used for reconstruction of tissue susceptibility maps in all subjects. Streaking detection was applied to evaluate streaking artifact in tissue susceptibility maps. In addition, an optimization process for QSM reconstruction by streaking detection was applied and was compared with matching noise level method.ResultsIt is shown that the proposed streaking detection technique effectively delineates streaking artifact in tissue susceptibility maps. In QSM reconstruction, optimization by streaking detection successfully determines the regularization factor that balances between streaking artifact suppression and tissue texture preservation. ROI analyses of brain tissue susceptibility show that optimization by streaking detection achieves results in good agreement with that from matching noise level method.ConclusionsStreaking detection enables direct visualization of streaking patterns in tissue susceptibility maps. It can be applied both for evaluating QSM reconstruction quality and for comparing different reconstruction algorithms. Furthermore, streaking detection can be incorporated into an optimization process of QSM reconstruction. Therefore, we conclude that the proposed method will add value to reconstruction of QSM.