Recent Publications by CFE Educators

OBJECTIVES

To understand how prioritization of treatment attributes and treatment choice varies by patient characteristics, we sought to specifically determine how demographic variables affect patient treatment preference.

PATIENTS AND METHODS

Male patients with urethral stricture disease participated in a choice-based conjoint (CBC) analysis exercise evaluating six treatment attributes associated with internal urethrotomy and urethroplasty. Demographic and past symptom data were collected. Stratified analysis of demographic variables, including age, education, income, was conducted using a mixed effect logistic regression model to evaluate the coefficient size and confidence intervals between the treatments attribute preferences of each strata.

RESULTS

169 patients completed the CBC exercise and were included in our analysis. Overall success of the procedure is the most important treatment attribute to patients and this persists across strata. Older patients (≥65) express preferences for better success rates and fewer future procedures, whereas younger patients prefer a less invasive approach and are more willing to accept additional procedures if needed. Patients with lower levels of education preferred open reconstruction and had a stronger preference against multiple future procedures, whereas those with higher levels of education preferred endoscopic treatment and had a less strong preference against multiple future procedures. Low-income individuals express statistically significant stronger negative preferences against high copay costs compared to high-income individuals.

CONCLUSION

These results can help to inform physicians' counseling about surgical management of urethral stricture disease to better align patient preferences with treatment selection and encourage shared decision making.

Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC) in carefully selected patients. Risk factors for tumors with poor prognostic features on explant have not been well described in a national cohort. We performed a retrospective cohort study of adult LT recipients with HCC transplanted from April 8, 2012 (when explant pathology in United Network for Organ Sharing [UNOS] became available) until September 30, 2014. We evaluated the association between listing diagnosis and other demographic factors with tumor features on explant using logistic regression. High-risk tumor features included the following: > 3 tumors, largest tumor > 5 cm, presence of vascular invasion, presence of metastases, and poor differentiation of tumor. In total, 3733 LT recipients with HCC who had complete explant data in UNOS were included. The median age was 60 years; 78% were male; and 68% were white. Of the primary non-HCC listing diagnoses, 2608 (70%) had hepatitis C virus (HCV); 271 (7%) had nonalcoholic steatohepatitis (NASH); 246 (7%) had alcoholic cirrhosis; and 189 (5%) had hepatitis B virus. Also, 1140 (31%) had evidence of ≥ 1 high-risk explant feature(s). The presence of ≥ 1 high-risk explant feature(s) was associated with HCC recurrence after transplant (odds ratio [OR], 5.00; P  0.001). Compared with HCV-associated HCC transplant recipients, individuals with NASH had lower likelihood of high-risk explant features (OR, 0.71; P = 0.02) after adjusting for covariables. Women were more likely to have high-risk explant features (OR, 1.23; P = 0.04). Diabetes mellitus (DM) was not associated with high-risk explant features. In conclusion, LT recipients with NASH-associated HCC had fewer high-risk tumor features on explant compared with HCV-associated HCC, despite having higher rates of DM and other potential risk factors for the development of HCC. Women had a higher likelihood of high-risk tumor features. Further study is warranted whether these differences are due to disease-specific or sex-specific influences on tumor biology or due to selection criteria for transplant. Liver Transplantation 23 1015-1022 2017 AASLD.

BACKGROUND

Ionizing radiation is a well-known carcinogen. Chromosome aberrations, and in particular micronuclei represent an early biological predictor of cancer risk. There are well-documented associations of micronuclei with ionizing radiation dose in some radiation-exposed groups, although not all. That associations are not seen in all radiation-exposed groups may be because cells with micronuclei will not generally pass through mitosis, so that radiation-induced micronuclei decay, generally within a few years after exposure.

METHODS

Buccal samples from a group of 111 male workers in Ukraine exposed to ionizing radiation during the cleanup activities at the Chornobyl nuclear power plant were studied. Samples were taken between 12 and 18 years after their last radiation exposure from the Chornobyl cleanup. The frequency of binucleated micronuclei was analyzed in relation to estimated bone marrow dose from the cleanup activities along with a number of environmental/occupational risk factors using Poisson regression adjusted for overdispersion.

RESULTS

Among the 105 persons without a previous cancer diagnosis, the mean Chornobyl-related dose was 59.5 mSv (range 0-748.4 mSv). There was a borderline significant increase in micronuclei frequency among those reporting work as an industrial radiographer compared with all others, with a relative risk of 6.19 (95% CI 0.90, 31.08, 2-sided p = 0.0729), although this was based on a single person. There was a borderline significant positive radiation dose response for micronuclei frequency with increase in micronuclei per 1000 scored cells per Gy of 3.03 (95% CI -0.78, 7.65, 2-sided p = 0.1170), and a borderline significant reduction of excess relative MN prevalence with increasing time since last exposure (p = 0.0949). There was a significant (p = 0.0388) reduction in MN prevalence associated with bone X-ray exposure, but no significant trend (p = 0.3845) of MN prevalence with numbers of bone X-ray procedures.

CONCLUSIONS

There are indications of increasing trends of micronuclei prevalence with Chornobyl-cleanup-associated dose, and indications of reduction in radiation-associated excess prevalence of micronuclei with time after exposure. There are also indications of substantially increased micronuclei associated with work as an industrial radiographer. This analysis adds to the understanding of the long-term effects of low-dose radiation exposures on relevant cellular structures and methods appropriate for long-term radiation biodosimetry.

OBJECTIVE

To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for chordoma and chondrosarcoma.

METHODS

Twenty consecutive patients with a histopathologic diagnosis of chordoma ( = 16) or chondrosarcoma ( = 4) treated between 2010 and 2016 were retrospectively identified. All patients underwent FSRT in five fractions to a median dose of 37.5 Gy (range: 25-40 Gy) and followed with serial magnetic resonance imaging. Overall survival (OS), local recurrence-free survival (LRFS), and event-free survival (EFS) were estimated using the Kaplan-Meier method.

RESULTS

With a median follow-up of 28 months after FSRT and 40 months after initial surgery, crude OS and LRFS were 90%. Nine patients (45%) reported grade 1-3 acute toxicity, and two patients (10%) experienced grade 4, 5 late toxicity. One patient previously treated with proton therapy died from radiation vasculopathy 9 months after FSRT. The use of FSRT for recurrent disease or in patients with prior radiation therapy was associated with significantly decreased EFS.

CONCLUSION

FSRT for chordoma and chondrosarcoma is associated with high rates of OS and local control. Although many patients experience acute toxicity, there is a low incidence of late toxicity or irreversible treatment related morbidity despite the frequency of prior radiotherapy in this population. FSRT is an effective adjuvant or salvage treatment for chordoma and chondrosarcoma.

BACKGROUND

Cardiovascular disease (CVD) is the number 1 killer of women in the United States, yet few younger women are aware of this fact. CVD campaigns focus little attention on physicians and their roles in assessing risk.

OBJECTIVES

In 2014, the Women's Heart Alliance (WHA) conducted a nationwide survey to determine barriers and opportunities for women and physicians with regard to CVD.

METHODS

From September 18 to 26, 2014, a total of 1,011 U.S. women (age 25 to 60 years) were interviewed using the GfK ("Gesellschaft für Konsumforschung" Knowledge Panel). From May 6 to 12, 2014, the e-Rewards Inc. Physician and Healthcare Professional Panel surveyed 200 primary care physicians (PCPs) and 100 cardiologists.

RESULTS

Overall, 45% of women were unaware that CVD is the number 1 killer of women; only 11% knew a woman who died from CVD. Overall, 45% of women reported it was common to cancel or postpone a physician appointment until losing weight. CVD was rated as the top concern by only 39% of PCPs, after weight and breast health. Only 22% of PCPs and 42% of cardiologists (p = 0.0477) felt extremely well prepared to assess CVD risk in women, while 42% and 40% felt well-prepared (p = NS), respectively. Few comprehensively implemented guidelines.

CONCLUSIONS

CVD was rated as the top concern less frequently than weight issues by both women and physicians. Social stigma particularly regarding body weight appeared to be a barrier. Physicians reported limited training and use of guideline assessment, whereas most supported a campaign and improved physician education. Campaigns should make CVD "real" to U.S. women, countering stereotypes with facts and validated assessments. Both community women and physicians endorsed investment in women's CVD research and physician education.

Intensive care unit (ICU) admission is a risk for multidrug-resistant (MDR) Pseudomonas aeruginosa, but factors specific to critically ill pneumonia patients are not fully characterized. Objective was to determine risk factors associated with MDR P. aeruginosa pneumonia among ICU patients. This was a retrospective case-control study of P. aeruginosa pneumonia in the ICU; cystic fibrosis and colonizers were excluded. Risk factors included comorbid conditions and prior healthcare exposure (anti-pseudomonal antibiotics, hospitalizations, nursing home, P. aeruginosa colonization/infection, mechanical ventilation). Of 200 patients, 47 (23.5%) had MDR P. aeruginosa pneumonia. Independent predictors for MDR were ≥24h antibiotics in the preceding 90days (carbapenems, fluoroquinolones, and piperacillin-tazobactam) (odds ratio, 3.6 [95% CI, 1.6-8.1]) and nursing home residence (2.3 [1.1-4.9]). MDR P. aeruginosa remains prevalent among ICU patients with pneumonia. Given poor outcomes with delayed therapy, patients should be thoroughly assessed for prior anti-pseudomonal antibiotic exposure and nursing home residency.

CONTEXT

A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown.

OBJECTIVE

We sought to identify new mechanistic indices that could inform more personalized management of PHPT.

DESIGN

Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables.

PATIENTS OR OTHER PARTICIPANTS

An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled.

MAIN OUTCOME MEASURES

Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior.

RESULTS

Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC503.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02).

CONCLUSIONS

Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT.

BACKGROUND

Evidence from adult psoriasis studies implicates an imbalance between regulatory and effector T cells, particularly T-17-producing T cells, in the pathogenesis of psoriasis. Little is known about the immunopathology of psoriasis in children.

OBJECTIVE

We sought to functionally characterize the inflammatory cell profiles of psoriatic plaques from pediatric patients and compare them with healthy, age-matched controls and adult psoriasis patients.

METHODS

Skin samples from pediatric psoriasis patients and healthy controls were analyzed by multiparameter flow cytometry to determine the dominant immune cell subsets present and cytokines produced.

RESULTS

Lesional tissue from pediatric psoriasis patients had significantly increased interleukin (IL) 22 derived from CD4 and CD8 cells compared with the tissues from healthy pediatric controls and adult psoriasis patients. Tissue from pediatric psoriasis patients had significantly less elevation of IL-17 derived from CD4 and CD8 cells compared with the tissue from adult psoriasis patients. In contrast with the lesions from adult patients, lesional skin in pediatric patients with psoriasis did not have increases in regulatory T cells.

LIMITATIONS

This is a pilot study, thus the sample size is small.

CONCLUSION

Significant differences in IL-17 and IL-22 expression were observed in the pediatric psoriasis patients compared with pediatric healthy controls and adult psoriasis patients. IL-22 might be relevant in the pathogenesis of pediatric psoriasis and represents a potential treatment target unique to pediatric psoriasis.

A 4-year-old boy with Goldenhar syndrome and severe obstructive sleep apnea does not tolerate nasal continuous positive airway pressure. Evaluation with imaging showed nasal obstruction with an inverted tooth. This case illustrates the importance of personalized evaluation and treatment plan in a child with Goldenhar syndrome.