Publications

OBJECTIVES

The healthcare burden of autoimmune hepatitis (AIH) in the United States has not been characterized. We previously showed that AIH disproportionately affects people of color in a single hospital system. The current study aimed to determine whether the same disparity occurs nationwide.

METHODS

We analyzed hospitalizations with a primary discharge diagnosis corresponding to the ICD-9 code for AIH in the National Inpatient Sample between 2008 and 2012. For each racial/ethnic group, we calculated the AIH hospitalization rate per 100,000 population and per 100,000 all-cause hospitalizations, then calculated a risk ratio compared to the reference rate among whites. We used multivariable logistic regression models to assess for racial disparities and to identify predictors of in-hospital mortality during AIH hospitalizations.

RESULTS

The national rate of AIH hospitalization was 0.73 hospitalizations per 100,000 population. Blacks and Latinos were hospitalized for AIH at a rate 69% (P<0.001) and 20% higher (P<0.001) than whites, respectively. After controlling for age, gender, payer, residence, zip code income, region, and cirrhosis, black race was a statistically significant predictor for mortality during AIH hospitalizations (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.43, 5.47).

CONCLUSIONS

Hospitalizations for AIH disproportionately affect black and Latino Americans. Black race is independently associated with higher odds of death during hospitalizations for AIH. This racial disparity may be related to biological, genetic, environmental, socioeconomic, and healthcare access and quality factors.

Despite achieving human immunodeficiency virus type 1 (HIV-1) RNA suppression below levels of detection and, for most, improved CD4+ T-cell counts, those aging with HIV experience excess low-level inflammation, hypercoagulability, and immune dysfunction (chronic inflammation), compared with demographically and behaviorally similar uninfected individuals. A host of biomarkers that are linked to chronic inflammation are also associated with HIV-associated non-AIDS-defining events, including cardiovascular disease, many forms of cancer, liver disease, renal disease, neurocognitive decline, and osteoporosis. Furthermore, chronic HIV infection may interact with long-term treatment toxicity and weight gain after ART initiation. These observations suggest that future biomarker-guided discovery and treatment may require attention to multiple biomarkers and, possibly, weighted indices. We are clinical trialists, epidemiologists, pragmatic trialists, and translational scientists. Together, we offer an operational definition of a biomarker and consider how biomarkers might facilitate progress along the translational pathway from therapeutic discovery to intervention trials and clinical management among people aging with or without HIV infection.

BACKGROUND

Nivolumab is approved for patients with metastatic renal cell carcinoma (mRCC) refractory to prior antiangiogenic therapy. The clinical activity of nivolumab in patients with non-clear cell RCC subtypes remains unknown as these patients were excluded from the original nivolumab trials.

METHODS

Patients from 6 centers in the United States who received at least one dose of nivolumab for non-clear cell mRCC between 12/2015 and 06/2017 were identified. A retrospective analysis including patient characteristics, objective response rate according to RECIST v1.1 and treatment-related adverse events (TRAEs) was undertaken.

RESULTS

Forty-one patients were identified. Median age was 58 years (33-82), 71% were male, and majority had ECOG PS 0 (40%) or 1 (47%). Histology included 16 papillary, 14 unclassified, 5 chromophobe, 4 collecting duct, 1 Xp11 translocation and 1 MTSCC (mucinous tubular and spindle cell carcinoma). Among 35 patients who were evaluable for best response, 7 (20%) had PR and 10 (29%) had SD. Responses were observed in unclassified, papillary and collecting duct subtypes. In the entire cohort, median follow-up was 8.5 months and median treatment duration was 3.0 months. Median PFS was 3.5 months and median OS was not reached. Among responders, median time to best response was 5.1 months, and median duration of response was not reached as only 2 out of 7 responders had disease progression during follow-up. TRAEs of any grade were noted in 37% and most commonly included fatigue (12%), fever (10%) and rash (10%). Nivolumab treatments were postponed in 34% and discontinued in 15% of patients due to intolerance. No treatment-related deaths were observed.

CONCLUSIONS

Nivolumab monotherapy demonstrated objective responses and was well tolerated in a heterogeneous population of patients with non-clear cell mRCC. In the absence of other data in this treatment setting, this study lends support to the use of nivolumab for patients with metastatic non-clear cell renal cell carcinoma.

OBJECTIVE

International guidelines recommend the use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI). The recommended duration of DAPT varies between guidelines. In this two-part study, we (1) performed a structured survey of 45 TAVI centres from around the world to determine if there is consensus among clinicians regarding antiplatelet therapy after TAVI; and then (2) performed a systematic review of all suitable studies (randomised controlled trials (RCTs) and registries) to determine if aspirin monotherapy can be used instead of DAPT.

METHODS

A structured electronic survey regarding antiplatelet use after TAVI was completed by 45 TAVI centres across Europe, Australasia and the USA. A systematic review of TAVI RCTs and registries was then performed comparing DAPT duration and incidence of stroke, bleeding and death. A variance weighted least squared metaregression was then performed to determine the relationship of antiplatelet therapy and adverse events.

RESULTS

82.2% of centres routinely used DAPT after TAVI. Median duration was 3 months. 13.3% based their practice on guidelines. 11 781 patients (26 studies) were eligible for the metaregression. There was no benefit of DAPT over aspirin monotherapy for stroke (P=0.49), death (P=0.72) or bleeding (P=0.91).

DISCUSSION

Aspirin monotherapy appears to be as safe and effective as DAPT after TAVI.