Metastatic Myxofibrosarcoma with Durable Response to Temozolomide Followed by Atezolizumab: A Case Report.

Myxofibrosarcoma (MFS) is a well-recognized histotype of soft tissue sarcomas that generally presents with localized disease. Herein, we describe the case of a patient with metastatic MFS who experienced durable response to sixth-line therapy with temozolomide. Upon further progression, his tumor was notable for a high tumor mutational burden, and he was subsequently treated with seventh-line immunotherapy, atezolizumab, achieving a second durable response. This case highlights the role of immunotherapy after administration of alkylating agents. Review of the literature indicates that recurrent tumors treated with alkylating agents often experience hypermutation as a means of developing resistance and that checkpoint inhibitors are subsequently effective in these tumors. KEY POINTS: To the authors' knowledge, this is the first report of a patient with myxofibrosarcoma with high tumor mutational burden after administration of temozolomide monotherapy. Hypermutation may be a resistance mechanism for patients with soft tissue sarcoma who develop resistance to alkylating agents. Checkpoint inhibition may be effective therapy in patients with soft tissue sarcoma with high tumor mutational burden as a consequence of alternate systemic therapy resistance.

Biomass and productivity of trematode parasites in pond ecosystems.

1. Ecologists often measure the biomass and productivity of organisms to understand the importance of populations and communities in the flow of energy through ecosystems. Despite the central role of such studies in the advancement of freshwater ecology, there has been little effort to incorporate parasites into studies of freshwater energy flow. This omission is particularly important considering the roles that parasites sometimes play in shaping community structure and ecosystem processes. 2. Using quantitative surveys and dissections of over 1600 aquatic invertebrate and amphibian hosts, we calculated the ecosystem-level biomass and productivity of trematode parasites alongside the biomass of free-living aquatic organisms in three freshwater ponds in California, USA. 3. Snails and amphibian larvae, which are both important intermediate trematode hosts, dominated the dry biomass of free-living organisms across ponds (snails = 3.2 g m(-2); amphibians = 3.1 g m(-2)). An average of 33.5% of mature snails were infected with one of six trematode taxa, amounting to a density of 13 infected snails m(-2) of pond substrate. Between 18% and 33% of the combined host and parasite biomass within each infected snail consisted of larval trematode tissue, which collectively accounted for 87% of the total trematode biomass within the three ponds. Mid-summer trematode dry biomass averaged 0.10 g m(-2), which was equal to or greater than that of the most abundant insect orders (coleoptera = 0.10 g m(-2), odonata = 0.08 g m(-2), hemiptera = 0.07 g m(-2) and ephemeroptera = 0.03 g m(-2)). 4. On average, each trematode taxon produced between 14 and 1660 free-swimming larvae (cercariae) infected snail(-1) 24 h(-1) in mid-summer. Given that infected snails release cercariae for 3-4 months a year, the pond trematode communities produced an average of 153 mg m(-2) yr(-1) of dry cercarial biomass (range = 70-220 mg m(-2) yr(-1)). 5. Our results suggest that a significant amount of energy moves through trematode parasites in freshwater pond ecosystems, and that their contributions to ecosystem energetics may exceed those of many free-living taxa known to play key roles in structuring aquatic communities.

Association of Perceived Futile or Potentially Inappropriate Care With Burnout and Thoughts of Quitting Among Health-Care Providers.

BACKGROUND: Futile or potentially inappropriate care (futile/PIC) has been suggested as a factor contributing to clinician well-being; however, little is known about this association. OBJECTIVE: To determine whether futile/PIC provision is associated with measures of clinician well-being. DESIGN: Cross-sectional, self-administered, online questionnaire. SETTING: Two New York City Hospitals. PARTICIPANTS: Attending physicians, residents, nurses, and physician assistants in the fields of internal medicine, surgery, neurology, or intensive care. EXPOSURE(S): Provision of perceived futile/PIC. MEASUREMENTS: Main outcomes included (1) clinician burnout, measured using the Physician Worklife Study screen; (2) clinician depression, measured using the Patient Health Questionnaire; and (3) intention to quit, measured using questions assessing thoughts of quitting and how seriously it is being considered. RESULTS: Of 1784 clinicians who received surveys, 349 participated. Across all clinicians, 91% reported that they either had or had possibly provided futile/PIC to a patient. Overall, 43.4% of clinicians screened positive for burnout syndrome, 7.8% screened positive for depression, and 35.5% reported thoughts of leaving their job as a result of futile/PIC. The amount of perceived futile/PIC provided was associated with burnout (odds ratio [OR] 3.8 [16-30 patients vs 1-2 patients]; 95% confidence interval [CI]: 1.1-12.8) and having thoughts of quitting (OR, 7.4 [16-30 patients vs 1-2 patients]; 95% CI: 2.0-27), independent of depression, position, department, and the number of dying patients cared for. CONCLUSIONS: A large majority of clinicians report providing futile/PIC, and such care is associated with measures of clinician well-being, including burnout and intention to quit.