Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practice

Part 2 of the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) offers drug-specific consensus recommendations based on both evidence and practical experience. These recommendations build upon the kidney function assessment and classification guidelines established in Part 1 of ADDIKD. Here we illustrate how dosing recommendations differ between ADDIKD and existing guidance for four commonly used drugs: methotrexate, cisplatin, carboplatin and nivolumab. We then describe how the recommendations can be distilled into practice points for methotrexate and cisplatin. While ADDIKD is a significant improvement from previous guidelines, adoption of this new guideline requires further endorsement from key external stakeholders, ‘change championing’ by clinicians locally and encouraging its integration into existing reference sources, clinical trial protocols and electronic prescribing systems

Characterizing wing tears in common pipistrelles (Pipistrellus pipistrellus): investigating tear distribution, wing strength, and possible causes

Bats have large, thin wings that are particularly susceptible to tearing. Anatomical specializations, such as fiber reinforcement, strengthen the wing and increase its resistance to puncture, and an extensive vasculature system across the wing also promotes healing. We investigated whether tear positioning is associated with anatomy in common pipistrelles (Pipistrellus pipistrellus). Wing anatomy was described using histological techniques, imaging, and material testing. Tear information, including type, position, time in rehabilitation, and possible causes, was collected from rehabilitators of injured bats across the United Kingdom. Results suggest that the position of the plagiopatagium (the most proximal wing section to the body), rather than its anatomy, influenced the number, location, and orientation of wing tears. While material testing did not identify the plagiopatagium as being significantly weaker than the chiropatagium (the more distal sections of the wing), the plagiopatagium tended to have the most tears. The position of the tears, close to the body and toward the trailing edge, suggests that they are caused by predator attacks, such as from a cat (Felis catus), rather than collisions. Consistent with this, 38% of P. pipistrellus individuals had confirmed wing tears caused by cats, with an additional 38% identified by rehabilitators as due to suspected cat attacks. The plagiopatagium had the lowest number of blood vessels and highest amounts of elastin fibers, suggesting that healing may take longer in this section. Further investigations into the causes of tears, and their effect on flight capabilities, will help to improve bat rehabilitation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Libraries Supporting Open Access: An Environmental Scan

https://digitalrepository.unm.edu/hslic-posters-presentations/1176/thumbnail.jp

Relative Body Size Influences Breeding Propensity in Fathead Minnows: Implications for Ecotoxicology Testing Procedure

Abstract Numerous factors affect the ability or choice of fishes to breed. For example, studies demonstrate that the appropriate amount of light, temperature, and food must be present before many species will breed. For some species, we are also aware of social factors that affect breeding, such as the size or colour of one's potential mates. Although studies on mate choice (i.e., choice of one potential mate over another) and factors affecting breeding are extensive, there remain significant gaps in our knowledge with regard to scientifically important species. For instance, the fathead minnow (Pimephales promelas), used by numerous researchers as a test subject in reproductive toxicology and behavioural ecology, has well established physical parameters known to facilitate breeding. Conversely, there is very little data describing social factors which may influence breeding. The purpose of the current study was to examine some of the factors affecting mate choice in the fathead minnow. Results indicate a consistent relationship between male and female size length and mass), which can be used to predict the probability of a couple's breeding potential. Specifically, we found that female minnows prefer larger males. In successful pairs there was a greater difference in size between the male and female as compared with unsuccessful pairs. The findings of this study could substantially improve methods for reproductive studies in laboratories or artificial streams by decreasing both the number of pairs tested against baseline performance criteria and the time needed to establish actively breeding individuals. This will decrease the cost and increase the efficiency of future studies, as well as add ecologically interesting knowledge to the literature regarding a scientifically important, ubiquitous, and representative North American fish species.</jats:p