Publications

OBJECTIVE

The rising incidence of oral tongue squamous cell carcinoma (OTSCC) in patients who have never smoked and the paucity of knowledge of its biological behavior prompted us to develop a new cell line originating from a never-smoker.

MATERIALS AND METHODS

Fresh tumor tissue of keratinizing OTSCC was collected from a 44-year-old woman who had never smoked. Serum-free media with a low calcium concentration were used in cell culture, and a multifaceted approach was taken to verify and characterize the cell line, designated UCSF-OT-1109.

RESULTS

UCSF-OT-1109 was authenticated by STR DNA fingerprint analysis, presence of an epithelial marker EpCAM, absence of human papilloma virus (HPV) DNA, and SCC-specific microscopic appearance. Sphere-forming assays supported its tumorigenic potential. Spectral karyotype (SKY) analysis revealed numerical and structural chromosomal abnormalities. Whole-exome sequencing (WES) identified 46 non-synonymous and 13 synonymous somatic single-nucleotide polymorphisms (SNPs) and one frameshift deletion in the coding regions. Specifically, mutations of CDKN2A, TP53, SPTBN5, NOTCH2, and FAM136A were found in the databases. Copy number aberration (CNA) analysis revealed that the cell line loses chromosome 3p and 9p, but lacks amplification of 3q and 11q (as does HPV-negative, smoking-unrelated OTSCC). It also exhibits four distinctive focal amplifications in chromosome 19p, containing 131 genes without SNPs. Particularly, 52 genes showed >3- to 4-fold amplification and could be potential oncogenic drivers.

CONCLUSION

We have successfully established a novel OTSCC cell line from a never-smoking patient. UCSF-OT-1109 is potentially a robust experimental model of OTSCC in never-smokers.

The Food and Drug Administration recommends rosuvastatin dosage reductions in Asian patients because pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects compared with Caucasian controls. Yet, no explanation for this ethnic difference has been confirmed. Here we show that rosuvastatin exposure in Asians and Whites does not differ significantly when all subjects are wild-type carriers for both solute carrier organic anion transporter 1B1 *1a and ATP-binding cassette subfamily G member 2 c.421 transporters in a 2-arm, randomized, cross-over rosuvastatin pharmacokinetics study in healthy white and Asian volunteers. For single rosuvastatin doses, AUC were 92.5 (±36.2) and 83.5 (±32.2) ng/mL × h and C were 10.0 (±4.1) and 7.6 (±3.0) ng/mL for Asians and Whites, respectively. When transporters were inhibited by intravenous rifampin, rosuvastatin AUC and C also showed no ethnic differences. Our study suggests that both SLCO1B1 and ABCG2 polymorphisms are better predictors of rosuvastatin exposure than ethnicity alone and could be considered in precision medicine dosing of rosuvastatin.

BACKGROUND

Hospital readmissions are common, expensive, and increasingly used as a metric for assessing quality of care. The relationship between index hospitalizations and specific outcomes among those readmitted remains largely unknown.

OBJECTIVES

Identify risk factors present during the index hospitalization associated with death or transition to hospice care during 30-day readmissions and examine the contribution of infection in readmissions resulting in death.

RESEARCH DESIGN

Retrospective cohort study.

SUBJECTS

A total of 17,716 30-day readmissions in an academic health system.

MEASURES

We used mixed-effects multivariable logistic regression models to identify risk factors associated with the primary outcome, in-hospital death, or transition to hospice during 30-day readmissions.

RESULTS

Of 17,716 30-day readmissions, 1144 readmissions resulted in death or transition to hospice care (6.5%). Risk factors identified included: age, burden, and type of comorbid conditions, recent hospitalizations, nonelective index admission type, outside hospital transfer, low discharge hemoglobin, low discharge sodium, high discharge red blood cell distribution width, and disposition to a setting other than home. Sepsis (OR=1.33; 95% CI, 1.02-1.72; P=0.03) and shock (OR=1.78; 95% CI, 1.22-2.58; P=0.002) during the index admission were associated with the primary outcome, and in-hospital mortality specifically. In patients who died, infection was the primary cause for readmission in 51.6% of readmissions after sepsis and 28.6% of readmissions after a nonsepsis hospitalization (P=0.009).

CONCLUSIONS

We identified factors, including sepsis and shock during the index hospitalization, associated with death or transition to hospice care during readmission. Infection was frequently implicated as the cause of a readmission that ended in death.

The National HIV/AIDS Strategy emphasizes rapid care linkage and engagement for HIV-infected individuals, though many adolescents are never tested, delay entering care, and frequently drop out. We conducted 183 staff interviews at 15 adolescent medicine clinics (baseline, n = 64; Year 1, n = 60; Year 2, = 59). We used a constant comparative thematic method to examine how providers approached and discussed care linkage/engagement. Qualitative analyses revealed differences in providers' conceptualizations of linkage and engagement. Providers saw linkage as mechanistic and health system driven. It was defined by number of clinic visits and involved relatively little youth agency. In contrast, providers defined engagement by youths' responsibility and participation in their own care. Linkage and engagement are related but distinct aspects of care that require different resources and levels of staff involvement. Integrating an understanding of these differences into future interventions will allow clinic staff to help youth improve long-term health outcomes.