Publications

BACKGROUND

Autoimmune hepatitis causes chronic hepatitis and often leads to cirrhosis and death without treatment. We wanted to see if having access to primary care or insurance prior to diagnosis is associated with better outcomes for patients in an urban, public hospital with mostly socioeconomically disadvantaged Hispanic patients.

METHODS

We did a retrospective study at our institution. Kaplan Meier survival analysis was done looking at transplant-free overall survival for patients diagnosed at our institution. The log-rank test was done to compare survival between patients with and without prior access to primary care, and between patients with and without insurance at diagnosis.

RESULTS

Overall 5- and 10-year transplant-free overall survival was 91% (95% CI, 83-100%) and 75% (95% CI, 50-99%), respectively. Patients with primary care prior to diagnosis had significantly better transplant-free overall survival than those without (log rank test p = 0.019). Patients with primary care also had better clinical markers at diagnosis. Having insurance at diagnosis was not associated with better outcomes.

CONCLUSIONS

Outcomes of autoimmune hepatitis are poor in our setting but access to primary care prior to diagnosis was associated with better outcomes. This is likely due to the important role that primary care plays in detecting disease and initiating treatment earlier. With the expansion of access to healthcare that the Affordable Care Act provides, future patients are likely to do better with even rare diseases like autoimmune hepatitis.

OBJECTIVE

Despite looming rheumatologist shortages and a growing number of patients with arthritis and other rheumatic conditions, nationwide estimates of access to rheumatology care have never been reported. We aimed to measure travel times as a proxy to access to care and to determine the individual and area-level factors associated with long travel times to rheumatologists in the U.S.

METHODS

We used Medicare Part B claims for the 2009 Medicare Chronic Condition Warehouse 5% rheumatoid arthritis/osteoarthritis cohort. Using Google Maps we estimated driving time from the center of a beneficiary's home ZIP code to the center of their rheumatologist's office ZIP code. We examined predictors of travel time ≥90 min in a series of generalized linear mixed models adjusting for rheumatologist supply, rurality, and individual patient characteristics including age, race, gender, and income.

RESULTS

We included 41,693 Medicare beneficiaries with 1 or more visits to a rheumatologist in 2009. The median estimated beneficiary travel time to a rheumatologist was 22 min [interquartile range (IQR): 12-40 min]. Overall, 7% of beneficiaries traveled 90 min or longer to visit a rheumatologist. Even after adjusting for covariates, independent predictors of long travel times included living in areas with no or low supply of rheumatologists and living in the Mountain region of the U.S.

CONCLUSIONS

A small but significant proportion of patients in the U.S. traveled very long distances to visit a rheumatologist, and most of these individuals resided in areas with no or low supplies of rheumatologists. These data suggest that addressing shortages in rheumatology care for patients in low-supply areas is a key target for improving access to rheumatologists.

BACKGROUND

Hepatitis C virus (HCV) infection may increase the risk of cardiovascular disease (CVD). We evaluated the association of chronic HCV infection and coronary atherosclerosis among participants in the Multicenter AIDS Cohort Study.

METHODS

We assessed 994 men with or without human immunodeficiency virus (HIV) infection (87 of whom had chronic HCV infection) for coronary plaque, using noncontrast coronary computed tomography (CT); 755 also underwent CT angiography. We then evaluated the associations of chronic HCV infection and HIV infection with measures of plaque prevalence, extent, and stenosis.

RESULTS

After adjustment for demographic characteristics, HIV serostatus, behaviors, and CVD risk factors, chronic HCV infection was significantly associated with a higher prevalence of coronary artery calcium (prevalence ratio, 1.29; 95% confidence interval [CI], 1.02-1.63), any plaque (prevalence ratio, 1.26; 95% CI, 1.09-1.45), and noncalcified plaque (prevalence ratio, 1.42; 95% CI, 1.16-1.75). Chronic HCV infection and HIV infection were independently associated with the prevalence of any plaque and of noncalcified plaque, but there was no evidence of a synergistic effect due to HIV/HCV coinfection. The prevalences of coronary artery calcium, any plaque, noncalcified plaque, a mixture of noncalcified and calcified plaque, and calcified plaque were significantly higher among men with an HCV RNA load of ≥2 × 10(6) IU/mL, compared with findings among men without chronic HCV infection.

CONCLUSIONS

Chronic HCV infection is associated with subclinical CVD, suggesting that vigilant assessments of cardiovascular risk are warranted for HCV-infected individuals. Future research should determine whether HCV infection duration or HCV treatment influence coronary plaque development.

T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently "knock out" genes and "knock in" targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4(+) T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ∼40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ∼20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.