TMPRSS2-ERG Fusions Are Strongly Linked to Young Patient Age in Low-grade Prostate Cancer

Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes—such as transmembrane protease, serine 2 (TMPRSS2)–v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion—and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11 152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2–ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ≤3 + 4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non–androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients.     

Delayed presentation of deep penetrating trauma to the subaxial cervical spine

Purpose

To present a rare case of deep penetrating neck trauma in which a retained foreign body in the cervical spine (a broken knife blade) resulted in delayed radicular injury. We describe the surgical management using a retrojugular approach.

Case report

Our patient sustained a stab wound to the supraclavicular triangle from a small pocketknife. He was initially managed in a local hospital by simple primary wound closure without any radiological examinations, and was discharged home. The patient re-consulted in a delayed fashion with mild local persistent neck pain. Subsequent radiological investigations revealed a foreign body (the broken blade of a pocket knife) embedded in the left neural foramen between the C6 and C7 vertebrae penetrating the disc space. The blade was lying between the left C7 nerve root and the ipsilateral vertebral artery (VA) at the transition of V1 and V2 segments. Initial neurological evaluation was normal. Some days later, the patient developed a delayed left C7 radicular deficit. We undertook urgent exploration along the wound corridor through a retrojugular, transforaminal approach with successful removal of the blade.

Discussion

To our knowledge, this is a unique case where a retained foreign body penetrated the soft tissues of the neck, embedding deep in the vertebral column without vascular, aerodigestive or significant primary neurological injury, while causing delayed neck pain and delayed onset radicular injury. We describe our surgical management for removal of the retained blade. The retrojugular approach gives excellent access to all of the important anatomical structures of the neck from an anterolateral approach.

     

Home Telehealth Uptake and Continued Use Among Heart Failure and Chronic Obstructive Pulmonary Disease Patients: a Systematic Review

Background

Home telehealth has the potential to benefit heart failure (HF) and chronic obstructive pulmonary disease (COPD) patients, however large-scale deployment is yet to be achieved.

Purpose

The aim of this review was to assess levels of uptake of home telehealth by patients with HF and COPD and the factors that determine whether patients do or do not accept and continue to use telehealth.

Methods

This research performs a narrative synthesis of the results from included studies.

Results

Thirty-seven studies met the inclusion criteria. Studies that reported rates of refusal and/or withdrawal found that almost one third of patients who were offered telehealth refused and one fifth of participants who did accept later abandoned telehealth. Seven barriers to, and nine facilitators of, home telehealth use were identified.

Conclusions

Research reports need to provide more details regarding telehealth refusal and abandonment, in order to understand the reasons why patients decide not to use telehealth.     

Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk prostate cancer

ObjectivesTreating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP.Materials and methodsThe Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level >20 ng/ml or Gleason score 8–10 or stage>cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy.ResultsCompared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56–0.64; P<0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P_interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27–0.54, P<0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57–0.66, P<0.001) among insured men.ConclusionsAA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers.     

23Na-magnetic resonance imaging of the human lumbar vertebral discs: in vivo measurements at 3.0 T in healthy volunteers and patients with low back pain

Background context¹H magnetic resonance imaging (MRI) of the spine can rule out common causes of low back pain (LBP), such as disc protrusions or nerve root compression; however, no significant causal relation exists between morphology and the extent of symptoms. Functional MRI techniques, such as ²³Na, may provide additional information, allowing indirect assessment of vertebral glycosaminoglycan concentrations, decreases in which are associated with early degenerative changes.PurposeTo evaluate ²³Na-MRI of asymptomatic healthy volunteers and symptomatic patients with LPB and correlate the results to the Pfirrmann classification of MRI disc morphology.Study designRetrospective cohort study at an academic medical center.Patient sampleTwo groups were studied: (1) 55 healthy volunteers (31 men, 24 women; mean age 28.8 years) and (2) 12 patients (6 men, 6 women; mean age: 35.3 years) with a recent history of LBP.MethodsLumbar spines of the aforementioned groups were examined on a 3.0 T MRI scanner with morphological ¹H and ²³Na imaging. Intervertebral disc (IVD) ²³Na at each level was normalized (²³Na_norm). Distribution and differences between mean ²³Na_norm corresponding to each Pfirrmann classification were evaluated in the two study groups (analysis of variance). Linear correlations between ²³Na_norm, body mass index (BMI), and age were assessed (Pearson correlation coefficient). Gender-dependent differences were evaluated (paired t test).Outcome measuresPhysiological measure: IVD ²³Na_norm as determined by ²³Na-MRI.ResultsA normal distribution of ²³Na_norm was confirmed for both groups (p=.072 and p=.073, respectively). The mean Pfirrmann score statistically significantly differed between them (p<.0001). ²³Na_norm was statistically significantly reduced in degenerated IVDs (Pfirrmann scores 4+5) (p<.0001). No statistically significant differences were seen for the mean ²³Na_norm of IVDs with the same Pfirrmann score in healthy volunteers and patients (.469<p<.967). Age (0.007<R²<0.202) and BMI (0.074<R²<0.288) showed either weak or no correlation to ²³Na_norm. Mean ²³Na_norm was significantly (p=.0002) greater in women relative to men.ConclusionsThe results underline the feasibility and robustness of ²³Na-MRI of human IVDs and affirm, in a large cohort, decreases in ²³Na IVD content seen with disc degeneration.     

Comparison of xenobiotic metabolizing enzyme activities in ex vivo human skin and reconstructed human skin models from SkinEthic

Skin function is not limited to a physical barrier. According to its total surface area, it is also considered as an extra-hepatic metabolizing organ. In vitro engineered human skins have been developed to replace limited ex vivo normal human skin samples (NHS). Thus, assessing and comparing skin models from SkinEthic [Episkin?, RHE? and the full thickness model (FTM)] with NHS in terms of metabolic capability are essential. The apparent activities of main cutaneous isoforms of cytochrome P450-dependent monooxygenases (CYP1A1/1B1, 2B6/2C18/2E1, 3A5/3A7), esterase, glutathione-S-[(GST), A, M, P, T], N-acetyl-(NAT1), uridinyl-diphosphate glucuronyl-(UDPGT 1A family) and sulfo-(SULT1A1) transferases were determined using probe substrates. Mean activities indicative of CYP1A1/1B1 (expressed as pmol/mg protein/6 h) in RHE? (2.8) and FTM (2.6) were very similar to NHS (3.0) while Episkin? showed a higher activity (9.1). Activities of CYP3A5/3A7 in FTM (3.3) and Episkin? (3.6) were similar to NHS (3.8) while activity in RHE? (13.3) was higher. CYP2B6/2C18/2E1 activity was below LOQ (0.5) in all skin models and NHS. Comparable intrinsic metabolic clearances were measured between NHS and skin models for esterase, UDPGT, GST and NAT1 activities. SULT1A1 activity toward probe substrates was not detected in skin models and observed at the limit of detection in NHS. Weak cytochrome P450-dependent monooxygenases, high esterase and transferase activities suggested that NHS and skin models exhibited limited functionalization and much greater detoxification (hydrolytic and conjugating) capacities. These results demonstrate that skin models are similar to NHS in terms of metabolic functionality toward xenobiotics investigated and useful tools to assess both the local efficiency and safety of cosmetics.