Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management

Abstract

Objective: To integrate gene expression profiling into the management of high-risk cutaneous squamous cell carcinoma (cSCC) within the National Comprehensive Cancer Network (NCCN) guidelines to improve risk-aligned management recommendations.

Methods: A cohort of 300 NCCN-defined high-risk cSCC patients, along with the American Joint Committee on Cancer (AJCC) T stage, Brigham and Women’s Hospital (BWH) T stage, and known patient outcomes were analyzed. Risk classifications using a validated 40-gene expression profile (40-GEP) test and T stage were applied to NCCN patient management guidelines. Risk-directed patient management recommendations within the NCCN guidelines framework were aligned based on risk for metastasis.

Results: Of the 300 NCCN high-risk cSCC patients, 159 (53.0%) were 40-GEP Class 1 and AJCC T1-T2, and 173 (57.7%) were Class 1 and BWH T1-2a, indicating low risk for metastasis and, thereby, suggesting low management intensity. The 40-GEP integration suggested high intensity management for only 24 (8.0%) patients (all Class 2B), and moderate intensity management for the remainder of the cohort.

Conclusions: The 40-GEP test can be integrated within existing NCCN guideline recommendations for managing cSCC patients to help refine risk-directed management decisions. Integration of the 40-GEP test would allow >50% of this NCCN-defined high-risk cohort to be managed with the lowest intensity recommendations within the broad NCCN guidelines. High intensity management was deemed risk-appropriate for a small subpopulation (8.0%). This study demonstrates that the 40-GEP test, in combination with T stage, has clinical utility to impact patient management decisions in NCCN high-risk cSCC for improving risk-aligned management within the NCCN guidelines framework.     

Future desire for children among women living with HIV in Atlanta,Georgia

Little is known regarding family planning desires among women living with HIV in the United States. This study aimed to identify factors influencing desire for children in the future among HIV-infected women in Atlanta, Georgia. HIV-infected women ages 18–45 completed an ACASI (audio computer-assisted self-interview) questionnaire. Chi-square, t-tests, and multivariate logistic regression evaluated factors associated with desire for future children. Of 181 participants, 62 (34.3%) expressed desire for children in the future, with increased desire among younger women (age <26) and those with seronegative partners. Concerns for horizontal and vertical HIV transmission were deterrents to future childbearing. Condom use and overall knowledge of transmission risk was low. Over a third of women desiring a child never discussed their desire with a physician. Misinformation regarding HIV transmission risks persists and is a notable concern influencing desire for children. Providers should reassess family planning desires regularly through integrated HIV care.     

Maternal controlling feeding behaviours and child eating in preschool‐aged children

Aim: This paper explored the relationship between maternal controlling feeding behaviours and child eating and weight in preschool‐aged children. Methods: Ninety mothers of 2‐ to 5‐year‐old children (M = 3.48, SD = 0.84, 54.4% males) completed self‐report measures assessing maternal controlling feeding behaviours, child eating patterns and weight. Results: Univariate analyses indicated that child food neophobia was associated with authoritarian feeding (r= 0.29), pressure to eat (r= 0.28) and restriction (r= 0.34). Child food pickiness was associated with authoritarian feeding (r= 0.35). No association was found between maternal feeding strategies and child weight. Multivariate regression analyses indicated that authoritarian feeding, restriction and pressure to eat were significantly associated with the variance in child food neophobia (adjusted R²= 12.6%) and pickiness (adjusted R²= 12.0%). Conclusions: The findings suggest that maternal control in feeding is associated with undesirable eating patterns in preschool‐aged children. Interventions targeting reduction in maternal controlling feeding may promote desirable eating patterns in preschool‐aged children.     

Recent Developments in the Role of Coenzyme Q10 for Coronary Heart Disease: a Systematic Review

Purpose of Review

This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease.

Recent Findings

CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control.

Summary

Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.

     

Impact of Kaposi sarcoma-associated herpesvirus (KSHV) burden and HIV coinfection on the detection of T cell responses to KSHV ORF73 and ORF65 proteins

Cellular immune responses to Kaposi sarcoma-associated herpesvirus (KSHV), the etiological agent of KS and several other malignancies, are incompletely characterized. We assessed KSHV-specific interferon- gamma enzyme-linked immunospot responses in a cohort of 154 individuals, using overlapping peptide sets spanning the KSHV-encoded latency-associated nuclear antigen (ORF73) and the minor capsid glycoprotein (ORF65). Among KSHV-seropositive subjects, ORF73-specific responses dominated over responses to ORF65 and were preferentially detected in human immunodeficiency virus-coinfected individuals who had elevated levels of cell-associated KSHV DNA, indicating that the viral antigen burden may have been driving these responses. Responses to both ORF73 and ORF65 were also detected in several KSHV-seronegative subjects who were at increased risk for KSHV infection, which demonstrates that cellular immunity can be found in the absence of detectable humoral responses. These data have implications for the reliable identification of KSHV infection and may help guide the design of immune-based therapeutic and prophylactic interventions.     

Thrombophilic polymorphisms in Israel

Three thrombophilic polymorphisms, FV G1691A, FII G20210A and MTHFR C677T were investigated in Israeli populations by FRET, (fluorescence resonance energy transfer) real-time PCR. We observe extensive variability in the frequencies of each of the polymorphisms, as has been observed in the study of other polymorphisms in these populations. Very high allele frequencies for FV G1691A (the highest 0.087 in Turkish and Greek Jews) and FII G20210A (the highest 0.061 in Georgian Jews) in some of the Israeli populations justify a clinical investigation to assess their risk for venous thrombosis. Principal Coordinates Analysis demonstrates that the Jewish populations are interspersed among the non-Jewish populations. The resemblance of some Jewish populations to certain non-Jewish populations coincides with findings based on classical markers.