Publications

BACKGROUND

Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms.

CASE PRESENTATION

This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies. Upon manifestation of worsening metastatic disease, the patient was initiated on a combination of ipilimumab and nivolumab. Within 2 months of starting immunotherapy, a robust partial response was observed. During the treatment course, the patient developed immune-related adverse effects including new diabetes mellitus, colitis, and hypothyroidism. The disease-specific survival was 26 months.

CONCLUSION

Combination immunotherapy may be an attractive option for HPV-related small cell head and neck cancers resistant to other treatment modalities and thus warrants further evaluation.

BACKGROUND

Despite significant interest in the collection of patient-reported outcomes to make care more patient-centered, few studies have evaluated implementation efforts to collect patient-reported outcomes from diverse patient populations.

OBJECTIVE

We assessed the collection of patient-reported outcomes from rheumatoid arthritis patients in an academic rheumatology clinic, using a paper and an online form through the electronic health record patient portal.

METHODS

We identified patients seen between 2012-2016 with ≥2 face-to-face encounters with a rheumatology provider and International Classification of Diseases codes for RA, ≥30 days apart. In 2013, our clinic implemented a paper version of the Patient Reported Outcome Measurement Information System (PROMIS) physical function form that was administered to patients upon their check-in at the clinic. In 2015, an online version of the form became available by way of the electronic health record patient portal to patients with active portal accounts. We compared the proportion of visits with documented PROMIS scores across age, race and ethnicity, and language and examined trends over time using a control chart.

RESULTS

We included 1078 patients with rheumatoid arthritis with 7049 in-person encounters at the rheumatology clinic over 4 years, with an average of 168 visits per month. Of the included patients, 80.4% of patients (867/1078) were female and the mean age was 58 (SD 16) years. The overall PROMIS physical function score documentation increased from 60.4% (1081/1791) of visits in 2013 to 74.4% (905/1217) of visits in 2016. Online score documentation increased from 10.0% (148/1473) in 2015 to 19.3% (235/1217) in 2016. African American patients were least likely to have a PROMIS physical function score recorded (55/88, 62.5% compared to 792/990, 80.0% for other racial or ethnic groups; P<.001). Compared with white patients, both African American and Hispanic patients were less likely to have active online electronic health record portal accounts (44/88, 50% and 90/157, 57.3% respectively, compared to 437/521, 83.9% of white patients; P<.001) and, once activated, less likely to use the online survey (6/44, 13.6% and 16/90, 17.8% respectively, compared to 135/437, 30.9% of white patients; P=.02). There was no significant difference in the proportion of any PROMIS physical function forms recorded between non-English vs English preferred patients. No significant differences were found across age or gender.

CONCLUSIONS

PROMIS physical function form completion improved overall from 2012-2016 but lagged among racial and ethnic minorities and non-English preferred patients. Future studies should address issues of portal access, enrollment, satisfaction, and persistence and focus on developing PRO implementation strategies that accommodate the needs and preferences of diverse populations.

Older homeless-experienced adults have low engagement in advance care planning (ACP) despite high morbidity and mortality. We conducted a cross-sectional analysis of a cohort of 350 homeless-experienced adults aged 50 and older in Oakland, California. We assessed the prevalence of potential surrogate decision-makers, ACP contemplation, discussions, and ACP documentation (surrogate designation, advance directives). We used multivariable logistic regression to examine factors associated with ACP discussions and documentation. The median age of the cohort was 59 (range 52-82), 75.2% were male, and 82.1% were black. Sixty-one percent reported a potential surrogate, 21.5% had discussed ACP, and 19.0% reported ACP documentation. In multivariable models, having 1 to 5 confidants versus none (adjusted odds ratio (aOR)=5.8, 95% confidence interval (CI)=1.7-20.0), 3 or more chronic conditions versus none (aOR=2.3, 95% CI=0.9-5.6), and a recent primary care visit (aOR=2.1, 95% CI=1.0-4.4) were associated with higher odds of ACP discussions and each additional 5 years of homelessness (aOR=0.7, 95% CI=0.5-0.9) with lower odds. Having 1 to 5 confidants (aOR=5.0, 95% CI=1.4-17.5), being black (aOR=5.5, 95% CI=1.5-19.5), and having adequate versus limited literacy (aOR=7.0, 95% CI=1.5-32.4) were associated with higher odds of ACP documentation and illicit drug use (aOR=0.3, 95% CI=0.1-0.9) with lower odds. Although the majority of older homeless-experienced adults have a potential surrogate, few have discussed or documented their ACP wishes; the odds of both were greater with larger social networks. Future interventions must be customized for individuals with limited social networks and address the instability of homelessness, health literacy, and the constraints of safety-net healthcare settings.

Regulatory T cells (Tregs) are essential for the maintenance of tolerance and immune homeostasis. In allogeneic hematopoietic stem cell transplantation (aHSCT), transfer of appropriate Treg numbers is a promising therapy for the prevention of graft-versus-host disease (GVHD). We have recently reported a novel approach that induces the marked expansion and selective activation of Tregs in vivo by targeting tumor necrosis factor receptor superfamily 25 (TNFRSF25) and CD25. A potential advance to promote clinical application of Tregs to ameliorate GVHD and other disorders would be the generation of more potent Treg populations. Here we wanted to determine if very low doses of Tregs generated using the "2-pathway" stimulation protocol via TL1A-Ig fusion protein and low-dose IL-2 (targeting TNFRSF25 and CD25, respectively) could be used to regulate preclinical GVHD. Analysis of such 2-pathway expanded Tregs identified higher levels of activation and functional molecules (CD103, ICOS-1, Nrp-1, CD39, CD73, il-10, and tgfb1) versus unexpanded Tregs. Additionally, in vitro assessment of 2-pathway stimulated Tregs indicated enhanced suppressor activity. Notably, transplant of extremely low numbers of these Tregs (1:6 expanded Tregs/conventional T cells) suppressed GVHD after an MHC-mismatched aHSCT. Overall, these results demonstrate that 2-pathway stimulated CD4 FoxP3 Tregs were quantitatively and qualitatively more functionally effective than unexpanded Tregs. In total, the findings in this study support the notion that such 2-pathway stimulated Tregs may be useful for prevention of GVHD and ultimately promote more widespread application of aHSCT in the clinic.

Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19 T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19 TRCs, likely including cholesterol-25-hydroxylase cells located at the T-zone perimeter, Cxcl9 TRCs in the T-zone and interfollicular region, CD34 SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase SCs in the medullary cords, and Nr4a1 SCs in several niches. These data help define how transcriptionally distinct LN SCs support niche-restricted immune functions and provide evidence that many SCs are in an activated state.