A second-generation microRNA-based assay for diagnosing tumor tissue origin

Background.

Cancers of unknown primary origin (CUP) constitute 3%–5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%–15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. Cancers of unknown/uncertain primary origins present major diagnostic and clinical challenges because the tumor tissue of origin is crucial for selecting optimal treatment. MicroRNAs are a family of noncoding, regulatory RNA genes involved in carcinogenesis. MicroRNAs that are highly stable in clinical samples and tissue specific serve as ideal biomarkers for cancer diagnosis. Our first-generation assay identified the tumor of origin based on 48 microRNAs measured on a quantitative real-time polymerase chain reaction platform and differentiated 25 tumor types.

Methods.

We present here the development and validation of a second-generation assay that identifies 42 tumor types using a custom microarray. A combination of a binary decision-tree and a k-nearest-neighbor classifier was developed to identify the tumor of origin based on the expression of 64 microRNAs.

Results.

Overall assay sensitivity (positive agreement), measured blindly on a validation set of 509 independent samples, was 85%. The sensitivity reached 90% for cases in which the assay reported a single answer (>80% of cases). A clinical validation study on 52 true CUP patients showed 88% concordance with the clinicopathological evaluation of the patients.

Conclusion.

The abilities of the assay to identify 42 tumor types with high accuracy and to maintain the same performance in samples from patients clinically diagnosed with CUP promise improved utility in the diagnosis of cancers of unknown/uncertain primary origins.     

Sources of information on the health effects of environmental tobacco smoke among African-American children and adolescents

Purpose: To determine the common sources of information regarding the effects of smoking on health and their relationship to knowledge, attitudes, and preventative efforts regarding exposure to environmental tobacco smoke (ETS) among urban African-American children and adolescents.

Methods: All students who were enrolled in Grades 5–12 in an urban public school district located in the greater metropolitan area of Detroit, Michigan were surveyed using a structured, written questionnaire that assessed sources of information on the health effects of smoking, as well as knowledge, attitudes, and preventive efforts with respect to exposure to ETS. The primary analytic procedures utilized in the study were correlation analysis and analysis of variance.

Results: The African-American students surveyed in this study received information regarding the health effects of smoking from many sources, most notably television, family, and teachers. Second, students who received information on the effects of smoking on health from family and external sources (teacher, parent’s friend, and religious leader) had higher overall knowledge, attitude, and preventive efforts scores than students who received information from other sources (friends, electronic media, and printed media). Finally, family influence was greater when parents were not smokers, and influenced elementary students more than middle school or high school students.

Conclusions: The active involvement of teachers, religious leaders, parents, and other influential adults should be elicited in tobacco education and prevention efforts to maximize their effectiveness.     

Cytogenetic status in newborns and their parents in Madrid: The BioMadrid study

Monitoring cytogenetic damage is frequently used to assess population exposure to environmental mutagens. The cytokinesis‐block micronucleus assay is one of the most widely used methods employed in these studies. In the present study we used this assay to assess the baseline frequency of micronuclei in a healthy population of father‐pregnant woman‐newborn trios drawn from two Madrid areas. We also investigated the association between micronucleus frequency and specific socioeconomic, environmental, and demographic factors collected by questionnaire. Mercury, arsenic, lead, and cadmium blood levels were measured by atomic absorption spectrometry. The association between micronucleated cell frequency and the variables collected by questionnaire, as well as, the risk associated with the presence of elevated levels of metals in blood, was estimated using Poisson models, taking the number of micronucleated cells in 1,000 binucleated cells (MNBCs) as the dependent variable. Separate analyses were conducted for the 110 newborns, 136 pregnant women, and 134 fathers in whom micronuclei could be assessed. The mean number of micronucleated cells per 1,000 binucleated cells was 3.9, 6.5, and 6.1 respectively. Our results show a statistically significant correlation in MNBC frequency between fathers and mothers, and between parents and newborns. Elevated blood mercury levels in fathers were associated with significantly higher MNBC frequency, compared with fathers who had normal mercury levels (RR:1.21; 95%CI:1.02–1.43). This last result suggests the need to implement greater control over populations which, by reason of their occupation or life style, are among those most exposed to this metal. Environ. Mol. Mutagen., 2010. © 2009 Wiley‐Liss, Inc.     

A comparison of mortality rates for buprenorphine versus methadone treatments for opioid use disorder

Introduction

In offending populations, prevalence rates of mental disorders are much higher than in the general population. Nevertheless, it is unclear whether mental disorders can improve the prediction of recidivism beyond actuarial risk assessment tools.

Methods

The present prospective-longitudinal study was conducted between 2001 and 2021 and included 1066 men convicted of sexual offenses in Austria. All participants were evaluated with actuarial risk assessment tools for the prediction of sexual and violent recidivism and the Structured Clinical Interview for Axis I and Axis II disorders. Sexual and violent reconvictions were assessed.

Results

Exhibitionism and an exclusive pedophilia showed the strongest correlations with sexual recidivism in the total sample. In the child related offense subsample additionally a narcissistic personality disorder was correlated with sexual recidivism. The strongest correlation with violent recidivism was found for an antisocial and borderline personality disorder. None of the mental disorders could improve the prediction of recidivism beyond actuarial risk assessment tools.

Conclusion

Common current actuarial risk assessment tools revealed good predictive accuracy in men convicted of sexual offenses. With few exceptions mental disorders were only weakly associated with recidivism, suggesting that there is no direct link between mental disorders and violent and sexual reoffending. Mental disorders should nevertheless be considered in treatment issues.     

Selective photothermolysis with a novel 1726 nm laser beam: A safe and effective solution for acne vulgaris

Background

Selective photothermolysis on sebaceous glands is an effective method for treating acne vulgaris (AV); however, safety, efficacy, and discomfort hinder its utilization in clinical settings.

Aims

The primary objective is to evaluate the safety and efficacy of a novel 1726 nm laser with contact cooling to treat AV.

Methods

Seventeen patients aged 18 to 36 were enrolled and treated in this IRB-approved, single-center, open-label study. Patients received up to three facial laser sessions up to seven weeks apart. Follow-up visits happened ten days post-session and at the 4 and 12 weeks following the final session. The investigator assessed the severity of device-related adverse events (AEs). Investigator Global Assessment (IGA) and inflammatory lesion counts (ILC) were used as metrics to evaluate acne resolution and skin condition enhancement. Patients' perspectives on satisfaction and comfort using this technology were assessed using Subject Experience Questionnaires (SEQ).

Results

Safety assessment showed mild and transient AEs. All subjects tolerated anesthetics-free treatments well, with a mean treatment discomfort score of 4.9 ± 1.5. Compared to baseline, a statistically significant reduction in ILC (p = 0.003) of 52% to 56% is achieved four to twelve weeks following treatment. Long-term follow-ups showed progressive improvement 24 months post-treatment with a 97% reduction in ILC. SEQs revealed high subject satisfaction (71%) with psychosocial improvement three months post-treatment.

Conclusion

The novel 1726 nm laser appears safe and effective for treating mild-to-severe acne. Acne resolution is apparent within the first month and progresses beyond the study duration.     

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for digestive neuroendocrine carcinoma

This ENETS guidance paper, developed by a multidisciplinary working group, provides up-to-date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11–12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first-line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second-line treatment. Immunotherapy plays a minor role in biomarker-unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease.