Citations

PURPOSE Patients with Waldenström macroglobulinemia (WM) have disparate outcomes. Newer therapies have emerged since the development of International Prognostic Scoring System, and MYD88 L265P mutation is now frequently assessed at diagnosis, warranting reexamination of the prognostic parameters. PATIENTS AND METHODS We reviewed records of 889 treatment-naïve patients with active WM, consecutively seen between January 01, 1996, and December 31, 2017, to identify clinical predictors of overall survival (OS) in univariate analyses. Patients with complete data for the parameters significant on the univariate analyses (n = 341) were included in a multivariable analysis to derive a prognostic model, subsequently validated in a multi-institutional cohort. RESULTS In the derivation cohort (n = 341), age (hazard ratio [HR], 1.9 [95% CI, 1.2 to 2.1]; P = .0009), serum lactate dehydrogenase (LDH) above upper limit of normal (HR, 2.3 [95% CI, 1.3 to 4.5]; P = .007), and serum albumin <3.5 g/dL (HR, 1.5 [95% CI, 0.99 to 2.3]; P = .056) were independently prognostic. By assigning a score of 1 point each to albumin <3.5 g/dL (HR, 1.5) and age 66-75 years (HR 1.4) and 2 points for age >75 years (HR, 2.6) or elevated LDH (HR, 2.3), four groups with distinct outcomes were observed on the basis of the composite scores. Five-year OS was 93% for the low-risk (score 0), 82% for low-intermediate risk (score 1), 69% for intermediate-risk (score 2), and 55% for the high-risk (score ≥3; P < .0001) groups. In the validation cohort (N = 335), the model maintained its prognostic value, with a 5-year OS of 93%, 90%, 75%, and 57% for the four groups, respectively ( P < .0001). CONCLUSION Modified Staging System for WM (MSS-WM), utilizing age, albumin, and LDH is a simple, clinically useful, and externally validated prognostic model that reliably risk-stratifies patients with symptomatic WM into four groups with distinct prognosis.

Abstract Purpose The Optimizing Performance Through Intrinsic Motivation and Attention for Learning (OPTIMAL) theory postulates that directing attention to the intended movement effect or outcome (external focus) is more effective than directing attention to the internal body motion or body part (internal focus). This study compared external versus internal focus of attention as novice students learned ultrasound-guided peripheral cannulation. The authors hypothesized that conditions promoting an external (vs internal) focus of attention would result in better performance on immediate and delayed (retention) testing. Method The authors conducted a randomized, experimental study from October 2022 to February 2023 comparing external and internal focus using ultrasound-guided peripheral venous cannulation followed by practice using an ultrasound training block. Undergraduate health science students performed 4 practice trials with instructions to focus on the needle tip (external focus) or their hands (internal focus), followed by immediate and delayed (retention) assessment 2 weeks later. The primary outcome was time to successful cannulation. Results were compared using Kaplan-Meier curves and parametric survival analysis regression (accelerated failure time) models. Results Seventy participants completed the immediate assessment. The external focus group completed successful cannulation a mean of 2.33 times faster (95% confidence interval [CI], 1.47–3.67; P &lt; .001) than those in the internal focus group (median time, 12.0 vs 29.5 seconds). Results also favored the external focus group during practice, with the external focus group successfully completing the task a mean of 1.83 times faster (95% CI, 1.04–3.21; P = .04) than the internal focus group. In the retention assessment, the external focus group successfully completed the task a mean of 2.37 times faster (95% CI, 1.19–4.74; P = .02) than the internal focus group. Conclusions External focus of attention compared with internal focus of attention improves medical motor skill learning in novice learners.

Abstract Bone metastases occur frequently in common malignancies such as breast and prostate cancer. They are responsible for considerable morbidity and skeletal-related events. Fortunately, there are now several systemic, focal, and targeted therapies that can improve quality and length of life, including radionuclide therapies. It is therefore important that bone metastases can be detected as early as possible and that treatment can be accurately and sensitively monitored. Several bone-specific and tumor-specific single-photon emission computed tomography and positron emission tomography molecular imaging agents are available, for detection and monitoring response to systemic therapeutics, as well as theranostic agents to confirm target expression and predict response to radionuclide therapies.

AbstractSeveral tools exist for assessing frailty in multiple myeloma (MM), but most are based on clinical trial datasets. In this study, we evaluate the prognostic impact of frailty based on the cumulative deficit frailty index (FI), and the prognostic impact of relationship and socioeconomic status (SES) in newly diagnosed MM patients. This is a retrospective study including 515 patients with MM seen at Mayo Clinic (Rochester, MN) at diagnosis between 2005–2018. The FI was calculated using patient-reported data on activities of daily living and comorbidity data. Items were scored as 0/0.5/1, with 1 indicating deficit. The FI was calculated by adding individual scores and dividing that by the number of non-missing items. Frailty was defined as FI ≥ 0.15; 61% were non-frail and 39% were frail. Frailty and non-married/relationship status were associated with higher disease stage, decreased likelihood of early transplantation, and independently associated with decreased survival. SES was not independently associated with survival. Frail patients reported worse scores for fatigue, pain, and quality of life. In conclusion, a cumulative deficit FI was associated with higher symptom burden and decreased survival in a real-world cohort of newly diagnosed MM patients. Social support has prognostic value and should be assessed in clinical practice.

Abstract Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements (“double hit”; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated. Here, we used custom targeted capture and/or whole-genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, although BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because 1 IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B-cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

Abstract Purpose Learner engagement is the energy learners exert to remain focused and motivated to learn. The Learner Engagement Instrument (LEI) was developed to measure learner engagement in a short continuing professional development (CPD) activity. The authors validated LEI scores using validity evidence of internal structure and relationships with other variables. Method Participants attended 1 of 4 CPD courses (1 in-person, 2 online livestreamed, and 1 either in-person or livestreamed) in 2018, 2020, 2021, and 2022. Confirmatory factor analysis was used to examine model fit for several alternative structural models, separately for each course. The authors also conducted a generalizability study to estimate score reliability. Associations were evaluated between LEI scores and Continuing Medical Education Teaching Effectiveness (CMETE) scores and participant demographics. Statistical methods accounted for repeated measures by participants. Results Four hundred fifteen unique participants attended 203 different CPD presentations and completed the LEI 11,567 times. The originally hypothesized 4-domain model of learner engagement (domains: emotional, behavioral, cognitive in-class, cognitive out-of-class) demonstrated best model fit in all 4 courses, with comparative fit index ≥ 0.99, standardized root mean square residual ≤ 0.031, and root mean square error of approximation ≤ 0.047. The reliability for overall scores and domain scores were all acceptable (50-rater G-coefficient ≥ 0.74) except for the cognitive in-class domain (50-rater G-coefficient of 0.55 to 0.66). Findings were similar for both in-person and online delivery modalities. Correlation of LEI scores with teaching effectiveness was confirmed (rho=0.58), and a small correlation was found with participant age (rho=0.19); other associations were small and not statistically significant. Using these findings, we generated a shortened 4-item instrument, the LEI Short Form. Conclusions This study confirms a 4-domain model of learner engagement and provides validity evidence that supports using LEI scores to measure learner engagement in both in-person and livestreamed CPD activities.

Background: Peripheral artery disease (PAD) is a prevalent condition affecting one in four patients with end stage renal disease (ESRD). Intermittent pneumatic compression (IPC) has proven benefits in PAD. We are conducting a trial testing the utility of IPC in the ESRD population by assessing the improvement in quality of life (QOL), functional limitation and walking performance from PAD-related symptoms. We aim to present our pilot results. Methods: Prospective single cohort study undergoing recruitment of outpatients at the hemodialysis (HD) unit of John H. Stroger Hospital. The calculated sample size is 78. PAD is confirmed by ankle-brachial index (ABI) and demographics obtained from interview and chart review. At baseline and post intervention, a Six-minute Walk Test (6MWT), Peripheral Artery Questionnaire (PAQ) and Walking Impairment Questionnaire (WIQ) are administered. The IPC device (Bio Arterial Plus) is used for intervention during HD. We present continuous variables as median (IQR) and categorical variables as percentage. Wilcoxon signed rank test was performed for comparison of results. Results: So far, 9 patients have completed intervention for the pilot study, 44% are men, the majority hispanic (66%), with age 48 (41-63) years. At baseline 66% of ABI were abnormal, all due to non-compressible PAD 1.46 (1.20-1.62). All patients have HTN, 44% diabetes, 33% hyperlipidemia and 33% heart failure. The median time of intervention is 70 (60-83) days. There was a significant difference in QOL measured by the WIQ (Fig.1), PAQ physical limitation (p=0.011), and PAQ social limitation (p=0.018). Although there was a trend towards benefit, no statistical difference was found on rest of objective and subjective measured parameters (p>0.05) Conclusions: Preliminary, IPC shows to improve many subsets of QOL in patients with ESRD and PAD. Given the small sample, improvement of walking distance remains elusive but with trends towards benefit.