Recent Publications by CFE Educators

Patients with T1 hepatocellular carcinoma (HCC; 1 lesion 2 cm) are currently not eligible for priority listing for liver transplantation (LT). A common practice is to wait without locoregional therapy (LRT) until tumor growth occurs from T1 to T2 (1 lesion 2-5 cm or 2-3 lesions ≤ 3 cm) to be eligible for listing with Model for End-Stage Liver Disease exception. We aimed to evaluate the intention to treat outcome of the "wait and not ablate" approach for nonresection candidates with T1 HCC until tumor growth to T2. The study included 114 patients with T1 HCC 1.0-1.9 cm followed by serial imaging every 3 months. Two investigators performed independent imaging reviews to confirm the diagnosis. Median increase in total tumor diameter was 0.14 cm/month. Probabilities of progression from T1 to directly beyond T2 without LT listing were 4.4% at 6 months and 9.0% at both 12 and 24 months. The 1- and 3-year survival was 94.5% and 75.5%. In multivariate analysis, predictors of rapid tumor progression, defined as a > 1 cm increase in total tumor diameter over 3 months, included alcoholic liver disease (odds ratio [OR], 6.52; P = 0.02) and Hispanic race (OR, 3.86; P = 0.047), whereas hepatitis B appeared to be protective (OR, 0.09; P = 0.04). By competing risks regression, predictors of exclusion from LT (with or without listing for LT under T2) were alpha-fetoprotein (AFP) ≥ 500 ng/mL (HR, 12.69; 95% confidence interval, 2.8-57.0; P = 0.001) and rapid tumor progression (HR, 5.68; P 0.001). In conclusion, the "wait and not ablate" approach until tumor growth from T1 to T2 before LT listing is associated with a 10% risk of tumor progression to directly beyond T2 criteria. However, patients with AFP ≥ 500 ng/mL and rapid tumor progression are at high risk for wait-list dropout and should receive early LRT.

IMPORTANCE

Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction.

OBJECTIVE

To estimate familial risk and heritability of cancer types in a large twin cohort.

DESIGN, SETTING, AND PARTICIPANTS

Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up.

EXPOSURES

Shared environmental and heritable risk factors among pairs of twins.

MAIN OUTCOMES AND MEASURES

The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death.

RESULTS

A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%).

CONCLUSIONS AND RELEVANCE

In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

OBJECTIVE

Infection is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Therapeutic practices have evolved over the past 15 years, but effects on infectious complications of SLE are unknown. We evaluated trends in hospitalizations for severe and opportunistic infections in a population-based SLE study.

METHODS

Data derive from the 2000 to 2011 United States National Inpatient Sample, including individuals who met a validated administrative definition of SLE. Primary outcomes were diagnoses of bacteremia, pneumonia, opportunistic fungal infection, herpes zoster, cytomegalovirus, or pneumocystis pneumonia (PCP). We used Poisson regression to determine whether infection rates were changing in SLE hospitalizations and used predictive marginals to generate annual adjusted rates of specific infections.

RESULTS

We identified 361,337 SLE hospitalizations from 2000 to 2011 meeting study inclusion criteria. Compared to non-SLE hospitalizations, SLE patients were younger (51 vs. 62 years), predominantly female (89% vs. 54%), and more likely to be racial/ethnic minorities. SLE diagnosis was significantly associated with all measured severe and opportunistic infections. From 2000 to 2011, adjusted SLE hospitalization rates for herpes zoster increased more than non-SLE rates: 54 to 79 per 10,000 SLE hospitalizations compared with 24 to 29 per 10,000 non-SLE hospitalizations. Conversely, SLE hospitalizations for PCP disproportionately decreased: 5.1 to 2.5 per 10,000 SLE hospitalizations compared with 0.9 to 1.3 per 10,000 non-SLE hospitalizations.

CONCLUSIONS

Among patients with SLE, herpes zoster hospitalizations are rising while PCP hospitalizations are declining. These trends likely reflect evolving SLE treatment strategies. Further research is needed to identify patients at greatest risk for infectious complications.

We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6-12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p = 0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p = 0.06). The average decrease in corticosteroid dose at follow-up was 20.3 mg ± 25.2 (p = 0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids.

BACKGROUND

Individuals with limited English proficiency (LEP) constitute an increasing share of the patient population in American healthcare settings. Few studies have described the patient's perspective on barriers to medical interpretation and experiences in the clinical setting.

METHODS

We conducted focus groups with 22 LEP Spanish-speaking adults. Focus groups were transcribed and analyzed in their original Spanish.

RESULTS

LEP patients face significant challenges when accessing health care services due to inadequate or insufficient access to professional interpreters. Predominant themes include: lack of interpreter availability, fear of disclosing limited English skills, and language discordant providers overestimating LEP patients' understanding of English. Many participants felt they had received poorer quality care.

CONCLUSIONS

LEP patients face multiple barriers to accessing adequate interpretation leading to a perceived worsening in the quality of care. In order to improve health outcomes for LEP patients, routine provision of adequate interpretation is essential.