High-dose chemotherapy with autologous stem-cell transplantation for relapsed metastatic germ cell tumors The Alberta experience.

INTRODUCTION: High-dose chemotherapy with autologous stem-cell transplantation (HDC-ASCT) is standard therapy for metastatic germ cell tumors (mGCTs) in patients whose disease progresses during or after conventional chemotherapy. We conducted a retrospective review of HDC-ASCT in relapsed mGCT patients in the province of Alberta, Canada, over the past two decades. METHODS: Patients with mGCTs who received HDC-ASCT at two provincial cancer referral centers from 2000-2018 were identified from institutional databases. Baseline clinical and treatment characteristics were collected, as well as overall survival (OS ) and disease-free survival (DFS). Relevant prognostic variables were analyzed. RESULTS: Forty-three patients were identified. The median age was 28 years (range 19-56). A majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty patients (47%) had poor-risk disease, as per The International Germ Cell Consensus Classification (IGCCC), at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% of patients, and 58% of ASCT patients received tandem transplants. Median followup after ASCT was 22 months (range 2-181). At last followup, 42% of patients were alive without disease, including 3/7 (43%) of patients with primary mediastinal disease. Two-year and five-year DFS/OS ratios were 44%/65% and 38%/45%, respectively. Median OS and DFS for all patients were 30.0 months (13.3-46.6) and 8.0 months (0.9-15.1), respectively. CONCLUSIONS: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Patients appeared to benefit regardless of primary site. Although limited by small sample size, we found a numerical difference in DFS and OS between second- and third-line HDC-ASCT and single vs. tandem ASCT.

Scientific contributions of citizen science applied to rare or threatened animals.

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.

La ciencia ciudadana contribuye a llenar vacíos en el monitoreo, lo que ayuda a la conservación de animales raros o amenazados. Sin embargo, la mayoría de los investigadores han usado publicaciones revisadas por pares para evaluar las contribuciones de la ciencia ciudadana. Cuantificamos un mayor espectro de las contribuciones de la ciencia ciudadana al monitoreo de animales raros y amenazados, incluyendo las contribuciones a la literatura gris, a las publicaciones revisada por pares y a las medidas de conservación (es decir, las acciones tomadas como resultado directo del monitoreo ciudadano). Buscamos proporcionar información generalizada sobre cómo los resultados de los estudios de monitoreo ciudadano es usado. También evaluamos los factores asociados con el éxito de los proyectos de ciencia ciudadana. Realizamos una búsqueda en línea para encontrar proyectos de ciencia ciudadana enfocados en especies raras o amenazadas y encuestamos a los gestores de estos proyectos sobre sus contribuciones y los factores que influyen sobre su éxito. El número de proyectos incrementó rápidamente a partir de 2010. De los proyectos de ciencia ciudadana, casi la mitad produjo al menos 1 publicación revisada por pares, el 64% produjo al menos una publicación en la literatura gris y el 64% derivó en al menos 1 medida de conservación. Las medidas de conservación abarcaron una gama extensa de acciones que incluyeron planes de gestión y mitigación, modificación del estado de amenaza, identificación y establecimiento de áreas protegidas, restauración del hábitat, control de especies invasoras, programas de reproducción en cautiverio y campañas de concientización. La longevidad, calidad de los datos y el tipo de colaboración explicaron de mejor manera las cantidades de todos los tipos de contribuciones científicas hechas por la ciencia ciudadana. Descubrimos que la ciencia ciudadana contribuyó sustancialmente al avance del conocimiento y la conservación, especialmente cuando los programas eran a largo plazo y contaban con estándares rigurosos de recolección y gestión de datos, y con colaboraciones multi o transdisciplinarias.

Expanded antigen-experienced CD160+CD8+effector T cells exhibit impaired effector functions in chronic lymphocytic leukemia.

BACKGROUND: T 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Our 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.

Using mounting, orientation, and design to improve bat box thermodynamics in a northern temperate environment.

Wildlife managers design artificial structures, such as bird houses and bat boxes, to provide alternative nesting and roosting sites that aid wildlife conservation. However, artificial structures for wildlife may not be equally efficient at all sites due to varying climate or habitat characteristics influencing thermal properties. For example, bat boxes are a popular measure employed to provide compensatory or supplementary roost sites for bats and educate the public. Yet, bat boxes are often thermally unstable or too cold to fulfill reproductive females needs in northern temperate environments. To help improve the thermodynamics of bat boxes, we tested the effect of (1) three mountings, (2) four orientations, and (3) twelve bat box designs on the internal temperature of bat boxes. We recorded temperatures in bat boxes across a climate gradient at seven sites in Quebec, Canada. Bat boxes mounted on buildings had warmer microclimates at night than those on poles and those facing east warmed sooner in the morning than those facing west or south. Our best new model based on passive solar architecture (Ncube PH1) increased the time in the optimal temperature range (22-40 °C) of targeted species by up to 13% compared to the most commonly used model (Classic 4-chamber) when mounted on a building with an east orientation (other designs presented in the Supplementary Information). Based on bioenergetic models, we estimated that bats saved up to 8% of their daily energy using the Ncube PH1 compared to the Classic 4-chamber when mounted on a building with an east orientation. We demonstrate that the use of energy-saving concepts from architecture can improve the thermal performance of bat boxes and potentially other wildlife structures as well.

Skeletal muscle density is an independent predictor of diffuse large B-cell lymphoma outcomes treated with rituximab-based chemoimmunotherapy.

BACKGROUND: While 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. METHODS: All 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. RESULTS: Of 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). CONCLUSIONS: SMD 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 is an independent predictor of response and outcomes in follicular lymphoma treated with chemoimmunotherapy.

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.