BackgroundWhile much cancer research focuses on tumours and their microenvironment, malignancies cause widespread physiologic changes. Cancer and treatment‐related sarcopenia, measured with quantitative imaging or as a decrease in overall body mass, are indicative of poor prognosis in elderly diffuse large B‐cell lymphoma (DLBCL) patients, skeletal muscle radiodensity (SMD) may be a better prognostic marker. SMD, a measure of muscle radiation attenuation on CT imaging, is more prognostic than sarcopenia or International Prognostic Index (IPI) scores in follicular lymphoma and multiple solid organ malignancies. Low SMD appears to correlate with fat accumulation in muscle and is associated with inflammation. This study set out to examine SMD's prognostic ability in DLBCL.MethodsAll DLBCL patients treated with rituximab‐containing therapy between 2004 and 2009 were compared to determine SMD's prognostic ability in this single centre, retrospective study. Pre‐treatment CT scans were used to measure SMD and muscle cross‐sectional area. Primary endpoints included progression free (PFS) and overall survival (OS) while objective response rates (ORR) were secondary.ResultsOf 224 evaluable patients, 116 were identified as having low SMD. Low SMD predicted poorer 5 year PFS, 60 vs. 81% (p = 0.001) and OS, 58 vs. 86% (p < 0.0001). SMD's prognostic ability retained significance in multivariate analysis taking into consideration the Revised International Prognostic Index (R‐IPI) and sex. Although high SMD was not predictive of ORR (95.4 vs. 91.4%, p = 0.17), it was strongly associated with radiographic complete response (85 vs. 66%, p = 0.0007). Contrary to previous findings, sarcopenia did not predict for poorer OS but suggested improved OS in elderly DLBCL patients (HR 0.38, p = 0.01).ConclusionsSMD is a novel prognostic (and potentially treatment predictive) marker independent of R‐IPI in DLBCL. It presents an inexpensive yet complementary assessment to R‐IPI for prognosticating DLBCL outcomes.
Skeletal muscle radio-density (SMD) measures muscle radiation attenuation (in Hounsfield Units, HU) on computed tomography (CT) scans. Low SMD is prognostic of poor survival in melanoma, however its significance is unknown for hematologic malignancies. We performed a single institution, retrospective review of all follicular lymphoma (FL) patients who received chemoimmunotherapy from 2004–2009. Patient demographics, FL International Prognostic Index 1 (FLIPI-1), progression free (PFS) and overall survival (OS) were collected as primary endpoints. Objective response rates (ORR) were secondary. SMD was calculated using pre-treatment CT scans. In 145 patients reviewed, median values were age 59, FLIPI-1 of 2, stage III, and 8 chemoimmunotherapy cycles received. Median PFS for those with low SMD (<36.6 and <33.1 HU for patients with BMI ≤ 25 and > 25 kg/m2, respectively) compared to those with high SMD was profoundly worse, 69.6 vs. 106.7 months (hazard ratio [HR] 1.85; p = 0.01), respectively. Median OS was not reached in patients with high SMD vs. 92.7 months in low SMD patients (HR 4.02; p = 0.0002). Multivariate analysis supported lower SMD’s OS detriment (HR = 3.40; p = 0.002) independent of FLIPI-1 (HR 1.46–2.76, p = 0.05) or gender. Low SMD predicted lower ORR, 83 vs. 96% (p = 0.01). SMD predicts survival independent of FLIPI-1 and potentially chemoimmunotherapy response. SMD is an inexpensive and powerful tool that can complement FLIPI-1.
BackgroundT cell exhaustion compromises antitumor immunity, and a sustained elevation of co-inhibitory receptors is a hallmark of T cell exhaustion in solid tumors. Similarly, upregulation of co-inhibitory receptors has been reported in T cells in hematological cancers such as chronic lymphocytic leukemia (CLL). However, the role of CD160, a glycosylphosphatidylinositol-anchored protein, as one of these co-inhibitory receptors has been contradictory in T cell function. Therefore, we decided to elucidate how CD160 expression and/or co-expression with other co-inhibitory receptors influence T cell effector functions in patients with CLL.MethodsWe studied 56 patients with CLL and 25 age-matched and sex-matched healthy controls in this study. The expression of different co-inhibitory receptors was analyzed in T cells obtained from the peripheral blood or the bone marrow. Also, we quantified the properties of extracellular vesicles (EVs) in the plasma of patients with CLL versus healthy controls. Finally, we measured 29 different cytokines, chemokines or other biomarkers in the plasma specimens of patients with CLL and healthy controls.ResultsWe found that CD160 was the most upregulated co-inhibitory receptor in patients with CLL. Its expression was associated with an exhausted T cell phenotype. CD160+CD8+ T cells were highly antigen-experienced/effector T cells, while CD160+CD4+ T cells were more heterogeneous. In particular, we identified EVs as a source of CD160 in the plasma of patients with CLL that can be taken up by T cells. Moreover, we observed a dominantly proinflammatory cytokine profile in the plasma of patients with CLL. In particular, interleukin-16 (IL-16) was highly elevated and correlated with the advanced clinical stage (Rai). Furthermore, we observed that the incubation of T cells with IL-16 results in the upregulation of CD160.ConclusionsOur study provides a novel insight into the influence of CD160 expression/co-expression with other co-inhibitory receptors in T cell effector functions in patients with CLL. Besides, IL-16-mediated upregulation of CD160 expression in T cells highlights the importance of IL-16/CD160 as potential immunotherapy targets in patients with CLL. Therefore, our findings propose a significant role for CD160 in T cell exhaustion in patients with CLL.
Unoccupied aerial vehicles (UAVs or drones) are becoming valuable tools in ecological research, as they offer a safer, cheaper and quieter alternative to large aircraft and may be more accurate than conventional methods (Hodgson et al., 2018;Scholten et al., 2019).Additionally, the increasing clarity of airspace regulations on UAV activity in many regions has lifted restrictions and simplified UAV use for wildlife science (Chabot & Bird, 2015;Gonzalez et al., 2016).However, wildlife has had adverse reactions to UAV presence
Citizen science is filling important monitoring gaps and thus contributing to the conservation of rare or threatened animals. However, most researchers have used peer‐reviewed publications to evaluate citizen science contributions. We quantified a larger spectrum of citizen science's contributions to the monitoring of rare or threatened animals, including contributions to the peer‐reviewed publications, gray literature and to conservation measures (i.e., actions taken as a direct result of citizen science monitoring). We sought to provide broad information on how results of studies of citizen science monitoring is used. We also evaluated factors associated with success of citizen science projects. We conducted a web search to find citizen science projects focusing on rare and threatened species and surveyed citizen science project managers about their contributions and factors influencing their success. The number of projects increased rapidly after 2010. Almost one‐half of the citizen science projects produced at least 1 peer‐reviewed publication, 64% produced at least 1 gray literature publication, and 64% resulted in at least 1 conservation measure. Conservation measures covered a wide range of actions, including management and mitigation plans, modification of threat status, identification and establishment of protected areas, habitat restoration, control of invasive species, captive breeding programs, and awareness campaigns. Longevity, data quality, and collaboration type best explained quantities of all types of scientific contributions of citizen science. We found that citizen science contributed substantially to knowledge advancement and conservation, especially when programs were long term and had rigorous data collection and management standards, and multidisciplinary or transdisciplinary collaborations.
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