Magnetic Resonance Imaging in Patients With Hearing Implants - Follow-up on Prevalence and Complications.

OBJECTIVE: To examine the number of magnetic resonance imaging (MRI) examinations performed in patients with hearing implants and to quantify side effects or complications related to this procedure. STUDY DESIGN: Questionnaire. SETTING: Tertiary referral center, academic hospital. PATIENTS: One thousand four hundred sixty-onepatients with an implanted hearing system. INTERVENTION: Patients were asked to complete a questionnaire either during a visit to the clinic (304) or by mail contact (1,157) between February 2018 and March 2019. MAIN OUTCOME MEASURES: Number of examinations by means of MRI per patient and number of side effects or complications. RESULTS: A total of 711 questionnaires were returned. After excluding nonvalid information on the questionnaire, 12.8% of patients were identified who had undergone an MRI after having received their hearing implant. Within this group of 91 patients, the most common precaution undertaken was a head bandage (69%). Side effects were mainly pain (37%), followed by anxiety (15%) and tinnitus (9%). The MRI had to be aborted in 14% and dislocation of the magnet occurred in 7% of examinations. CONCLUSIONS: Our data indicate that patients undergoing hearing implant surgery need better information about the limitations and requirements of MRI. The occurrence of side effects is likely as only half of the patients in our study group were completely free of symptoms. Dislocation of the implant magnet was observed in several cases, hence patients and physicians need to be educated about this potential complication.

Patient-reported outcomes feedback report for knee arthroplasty patients should present selective information in a simple design - findings of a qualitative study.

BACKGROUND: Technical innovation to assess patient-reported outcomes (PROs) facilitates their implementation in clinical practice. In particular, mobile applications (apps) allow PROs to be assessed outside of the clinical setting. A patient's health status can be remotely monitored and evaluated after discharge, and their recovery process tracked. This is of particular interest for patients after knee arthroplasty, as the recovery phase after surgery usually takes place in an outpatient setting and requires a high level of patient engagement. Providing results of PRO assessments to patients in the form of a feedback report could increase patient engagement and may improve communication between health care professionals and patients. The aim of the study is to develop a PRO feedback report for mobile devices that is comprehensible and provides valuable information for patients after knee arthroplasty. RESULTS: In an iterative development process, our expert group developed two preliminary feedback reports (a text-based version and a graphical display) based on previous research results and practical experience. In a second step, we discussed these reports with orthopedic patients (n = 8) in terms of comprehensibility and value using semi-structured interviews and cognitive debriefing methods. Participants assessed the reports as informative, but had some difficulties in fully comprehending all of the information provided. Based on the feedback from patients, we modified both versions and reduced complexity to increase comprehensibility. CONCLUSIONS: A PRO feedback report for patients for mobile app use has to take account of the heterogeneous user group, particularly demographics such as age and experience with mobile devices. Information should be presented in a simple way to be comprehensible and of value to patients. Technological advancements allow a simple default report to be set, something which enables patients interested in additional information to make customizations.

Putative Breast Cancer Driver Mutations in TBX3 Cause Impaired Transcriptional Repression.

The closely related T-box transcription factors TBX2 and TBX3 are frequently overexpressed in melanoma and various types of human cancers, in particular, breast cancer. The overexpression of TBX2 and TBX3 can have several cellular effects, among them suppression of senescence, promotion of epithelial-mesenchymal transition, and invasive cell motility. In contrast, loss of function of TBX3 and most other human T-box genes causes developmental haploinsufficiency syndromes. Stephens and colleagues (1), by exome sequencing of breast tumor samples, identified five different mutations in TBX3, all affecting the DNA-binding T-domain. One in-frame deletion of a single amino acid, p.N212delN, was observed twice. Due to the clustering of these mutations to the T-domain and for statistical reasons, TBX3 was inferred to be a driver gene in breast cancer. Since mutations in the T-domain generally cause loss of function and because the tumorigenic action of TBX3 has generally been attributed to overexpression, we determined whether the putative driver mutations had loss- or gain-of-function properties. We tested two in-frame deletions, one missense, and one frameshift mutant protein for DNA-binding in vitro, and for target gene repression in cell culture. In addition, we performed an in silico analysis of somatic TBX mutations in breast cancer, collected in The Cancer Genome Atlas (TCGA). Both the experimental and the in silico analysis indicate that the observed mutations predominantly cause loss of TBX3 function.

A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro.

The close resemblance of carbon nanotubes to asbestos fibers regarding their high aspect ratio, biopersistence and reactivity increases public concerns on the widespread use of these materials. The purpose of this study was not only to address the acute adverse effects of industrially produced multiwalled carbon nanotubes (MWCNTs) on human lung and immune cells in vitro but also to further understand if their accumulation and biopersistence leads to long-term consequences or induces adaptive changes in these cells. In contrast to asbestos fibers, pristine MWCNTs did not induce overt cell death in A549 lung epithelial cells and Jurkat T lymphocytes after acute exposure to high doses of this material (up to 30 µg/ml). Nevertheless, very high levels of reactive oxygen species (ROS) and decreased metabolic activity were observed which might affect long-term viability of these cells. However, the continuous presence of low amounts of MWCNTs (0.5 µg/ml) for 6 months did not have major adverse long-term effects although large amounts of nanotubes accumulated at least in A549 cells. Moreover, MWCNTs did not appear to induce adaptive mechanisms against particle stress in long-term treated A549 cells. Our study demonstrates that despite the high potential for ROS formation, pristine MWCNTs can accumulate and persist within cells without having major long-term consequences or inducing adaptive mechanisms.

Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation.

Azoles are used as fungicides in agriculture or antifungal drugs in medicine. Their therapeutic activity is based on the inhibition of fungal lanosterol-14alpha-demethylase (CYP51). Azoles are also used for the treatment of estrogen-dependent diseases, e.g. in breast cancer therapy. Inhibition of CYP19 (aromatase) is the working principle for tumor therapy, but is an unwanted side effect of azoles used as fungicides or antifungal drugs. The inhibition of recombinant human CYP19 by 21 azoles in use for the three different purposes was investigated using the natural substrate testosterone. Estradiol product formation was measured by a newly developed and fully validated analytical method based on liquid chromatography-tandem mass spectrometry utilizing photospray ionization (APPI). Potency of enzyme inhibition was expressed in terms of IC50 concentrations. The two cytostatic drugs fadrozole and letrozole were the most potent inhibitors. However, azoles used as fungicides, e.g. prochloraz, or as antifungal drugs, e.g. bifonazole, were almost as potent inhibitors of aromatase as the drugs used in tumor therapy. Comparison of plasma concentrations that may be reached in antifungal therapy do not allow for large safety factors for bifonazole and miconazole. The IC50 values were compared to data obtained with other substrates, such as the pseudo-substrate dibenzylfluorescein (DBF). A high correlation was found, indicating that the fluorescence assay with DBF can well be used for potency ranking and screening of chemicals for aromatase inhibition. The data for antifungal drugs show that side effects on steroid hormone synthesis in humans due to inhibition of aromatase should be considered.