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Background The California End of Life Option Act (EOLOA), which legalized physician-assisted death (PAD), became effective in 2016. The EOLOA does not require a mental health consultation in all cases nor does it state the standards for the mental health assessment. University of California, San Francisco Medical Center (UCSFMC) policy makers decided to require a mental health assessment of all patients seeking PAD under the EOLOA. Objectives The Department of Psychiatry was tasked with developing a standard protocol for the mental health assessment of patients seeking PAD. Methods Members of the consultation-liaison (C-L) service developed a document to guide members in completing the mental health evaluations for patients requesting PAD. Results A committee at UCSFMC developed a clinical protocol informed by the law with an additional local expectation of an evaluation by a psychiatrist or clinical psychologist. The C-L psychiatry group at UCSF developed a standard protocol for the psychiatric assessment for use by clinicians performing these assessments. Attention to the cognitive, mood, and decisional capacity status pertinent to choosing PAD is required under the clinical guidance document. Case vignettes of 6 patients evaluated for PAD are presented. Conclusions The local adoption of the California EOLOA by UCSFMC requires a mental health assessment of all patients requesting EOL services at UCSF. The clinical guideline for these assessments was locally developed, informed by the literature on EOL in other jurisdictions where it has already been available.

Background. The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention. Methods. To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX). Results. We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 Conclusion. Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.

Natural killer (NK) cells contribute to clinical responses in patients treated with rituximab, but the rules determining NK-cell responsiveness to mAb therapies are poorly defined. A deeper understanding of the mechanisms responsible for antibody-dependent cellular cytotoxicity (ADCC) could yield useful biomarkers for predicting clinical responses in patients. Unlicensed NK cells, defined as NK cells lacking expression of an inhibitory KIR for self-HLA class I ligands, are hyporesponsive in steady state, but are potent effectors in inflammatory conditions. We hypothesized that antitumor antibodies such as rituximab can overcome NK-cell dependence on licensing, making unlicensed NK cells important for clinical responses. Here, we examined the influences of variations in KIR and HLA class I alleles on in vitro responses to rituximab. We tested the clinical significance in a cohort of patients with follicular lymphoma treated with rituximab-containing mAb combinations, and show that rituximab triggers responses from all NK-cell populations regardless of licensing. Neither IL2 nor accessory cells are required for activating unlicensed NK cells, but both can augment rituximab-mediated ADCC. Moreover, in 101 patients with follicular lymphoma treated with rituximab-containing mAb combinations, a “missing ligand” genotype (predictive of unlicensed NK cells) is associated with a higher rate of progression-free survival. Our data suggest that the clinical efficacy of rituximab may be driven, in part, by its ability to broaden the NK-cell repertoire to include previously hyporesponsive, unlicensed NK cells. A “missing ligand” KIR and HLA class I genotype may be predictive of this benefit and useful for personalizing treatment decisions in lymphomas and other tumors. Cancer Immunol Res; 2(9); 878–89. ©2014 AACR.

Proceedings of the 4th Annual Meeting of the Berkeley Linguistics Society (1978), pp. 352-359