In lung transplant candidates, palliative care and opioids in particular can be safely provided without compromising eligibility for transplantation. Palliative care should not be delayed until a patient is deemed ineligible for transplant.

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The Sclerotiniaceae (Ascomycotina, Leotiomycetes) is a relatively recently evolved lineage of necrotrophic host generalists, and necrotrophic or biotrophic host specialists, some latent or symptomless. We hypothesized that they inherited a basic toolbox of genes for plant symbiosis from their common ancestor. Maintenance and evolutionary diversification of symbiosis could require selection on toolbox genes or on timing and magnitude of gene expression. The genes studied were chosen because their products have been previously investigated as pathogenicity factors in the Sclerotiniaceae. They encode proteins associated with cell wall degradation: acid protease 1 (acp1), aspartyl protease (asps), and polygalacturonases (pg1, pg3, pg5, pg6), and the oxalic acid (OA) pathway: a zinc finger transcription factor (pac1), and oxaloacetate acetylhydrolase (oah), catalyst in OA production, essential for full symptom production in Sclerotinia sclerotiorum. Site-specific likelihood analyses provided evidence for purifying selection in all 8 pathogenicity-related genes. Consistent with an evolutionary arms race model, positive selection was detected in 5 of 8 genes. Only generalists produced large, proliferating disease lesions on excised Arabidopsis thaliana leaves and oxalic acid by 72 hours in vitro. In planta expression of oah was 10–300 times greater among the necrotrophic host generalists than necrotrophic and biotrophic host specialists; pac1 was not differentially expressed. Ability to amplify 6/8 pathogenicity related genes and produce oxalic acid in all genera are consistent with the common toolbox hypothesis for this gene sample. That our data did not distinguish biotrophs from necrotrophs is consistent with 1) a common toolbox based on necrotrophy and 2) the most conservative interpretation of the 3-locus housekeeping gene phylogeny – a baseline of necrotrophy from which forms of biotrophy emerged at least twice. Early oah overexpression likely expands the host range of necrotrophic generalists in the Sclerotiniaceae, while specialists and biotrophs deploy oah, or other as-yet-unknown toolbox genes, differently.

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BackgroundPrimary cardiac sarcoma (PCS) is a rare but often fatal disease. The current study aimed to analyze the impact of baseline demographics, local and systemic therapies in a contemporary cohort.MethodsClinical records of PCS across six institutions in three continents were reviewed. Kaplan‐Meier method was used to estimate survival. Cox proportional hazard model was used to determine variables impacting progression‐free survival (PFS) or overall survival (OS).ResultsSixty‐one patients with PCS (1996‐2016) were identified. The median age at diagnosis was 46 (range 18‐79); 36% (n = 22) presented with metastatic disease. The most common histology was angiosarcoma (n = 24, 39%). A total of 46 patients received surgery (75%) but only 5 (8%) patients achieved R0 resection. Multi‐modality treatment to the primary tumor was given to 28 patients (46%; localized disease 23/39 (59%); metastatic disease 5/22 (23%)). The median OS for the entire cohort was 17.5 months (95% CI 9.5‐20.6), with seven (11%) patients surviving longer than 36 months. On multi‐variate analysis, age <65 (P = 0.01) was the only significant favorable prognostic factor. For first‐line palliative chemotherapy, the median PFS was 4.4 months (95% CI 2.9‐7.7 months). The best response for first‐line chemotherapy was 32% (CR = 1, PR = 9). No significant improvement in OS was identified in patients presenting throughout the 20‐year period of this review.ConclusionYounger age at diagnosis was associated with improved outcome although the prognosis of PCS remains poor. Given the lack of improvement in survival, further dedicated research is required.

LT recipients referred for PC co-management typically receive comfort medications and avoid the aggressive end-of-life care usually reported for this population. The effect of PC interventions on patient quality of life requires further study.

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