Search

Background: Plasma cell leukemia (PCL) is a rare monoclonal gammopathy, associated with short survival. Because of its very low incidence, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand the clinical features, prognostic factors, and efficacy of modern treatments in both primary PCL (pPCL) and secondary PCL (sPCL). Methods: We performed a retrospective, multicenter study of patients diagnosed with PCL, defined as circulating plasma cells ≥20% of total leukocytes and/or ≥2 × 109/L. Results: We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. The median progression‐free survival (PFS) to frontline treatment and overall survival (OS) were, respectively, 4.8 (95% CI, 0.4–9.2) and 18.3 months (95% CI, 0.0–39.0) for pPCL and 0.8 (95% CI, 0.5–1.1) and 1.2 months (95% CI, 0.9–1.5) for sPCL (both p < 0.001). We observed no improvement in OS over time (2005–2012 vs. 2013–2020, p = 0.629 for pPCL and p = 0.329 for sPCL). Finally, our data suggested that sPCL originates from a high‐risk multiple myeloma (MM) population with a short OS (median 30.2 months), early relapse after stem cell transplant (median 11.9 months) and a high proportion of patients with multiple cytogenetic abnormalities (36% with ≥2 abnormalities). Conclusions: This study is one of the largest PCL cohorts reported. We are also the first to investigate characteristics of MM before its transformation into sPCL and demonstrate that high‐risk biologic features already present at the time of MM diagnosis. Moreover, our data highlights the lack of improvement in PCL survival in recent years and the urgent need for better treatment options. [ABSTRACT FROM AUTHOR]

Fatigue at individual joints is known to affect interjoint coordination during repetitive multijoint tasks. However, how these coordination adjustments affect overall task stability is unknown. Twelve participants completed a repetitive pointing task at rest and after fatigue of the shoulder, elbow, and trunk. Upper-limb and trunk kinematics were collected. Uncontrolled manifold framework was applied to a kinematic model to link elemental variables to endpoint fingertip position. Mixed and one-way analysis of variances determined effects (phase and fatigue location) on variance components and synergy index, respectively. The shoulder fatigue condition had the greatest impact in causing increases in variance components and a decreased synergy index in the late phase of movement, suggesting more destabilization of the interjoint task caused by shoulder fatigue. [ABSTRACT FROM AUTHOR]

Females demonstrate greater fatigue resistance during a range of exercise modalities; however, this may be confounded by the lower mechanical work completed. Accordingly, this study examined the sex-specific peripheral and central fatigue mechanisms during repeated all-out cycling and whether they are affected by total mechanical work performed. A total of 26 healthy young adults (12 females) performed 10 × 10 s all-out cycling interspersed by 30 s passive recovery. Metabolic responses, peripheral and central fatigue, were quantified via changes in pre- to post-exercise blood lactate, potentiated quadriceps twitch force (and contractile properties) evoked via supramaximal electrical stimulation of the femoral nerve, and voluntary activation of the knee extensors, respectively. During exercise, mechanical work, vastus lateralis muscle activation (via surface electromyography), and deoxygenation (via near-infrared spectroscopy) were recorded. Sex comparison analyses were performed before and after statistically controlling for total mechanical work (via ANCOVA). Mechanical work and muscle activation plateaued at similar sprint repetition (sprint 5) and voluntary activation change (pre vs. post) was similar between the sexes. Females, however, showed lower %work decrement (i.e., fatigability; P = 0.037) and peripheral responses as evident by lower reductions in quadriceps twitch force (P < 0.001) and muscle deoxygenation (P = 0.001). Adjusting for total mechanical work did not change these sex comparison results. We show that females' greater fatigue resistance during repeated all-out cycling may not be attributed to the greater total mechanical work performed but could be mediated by lower peripheral fatigue in the knee extensor muscles. [ABSTRACT FROM AUTHOR]