A quantitative polymerase chain reaction based method for molecular subtype classification of urinary bladder cancer-Stromal gene expressions show higher prognostic values than intrinsic tumor genes.

Transcriptome-based molecular subtypes of muscle-invasive bladder cancer (MIBC) have been shown to be both prognostic and predictive, but are not used in routine clinical practice. We aimed to develop a feasible, reverse transcription quantitative polymerase chain reaction (RT-qPCR)-based method for molecular subtyping. First, we defined a 68-gene set covering tumor intrinsic (luminal, basal, squamous, neuronal, epithelial-to-mesenchymal, in situ carcinoma) and stromal (immune, extracellular matrix, p53-like) signatures. Then, classifier methods with this 68-gene panel were developed in silico and validated on public data sets with available subtype class information (MD Anderson [MDA], The Cancer Genome Atlas [TCGA], Lund, Consensus). Finally, expression of the selected 68 genes was determined in 104 frozen tissue samples of our MIBC cohort by RT-qPCR using the TaqMan Array Card platform and samples were classified by our newly developed classifiers. The prognostic value of each subtype classification system and molecular signature scores were assessed. We found that the reduced marker set combined with the developed classifiers were able to reproduce the TCGA II, MDA, Lund and Consensus subtype classification systems with an overlap of 79%, 76%, 69% and 64%, respectively. Importantly, we could successfully classify 96% (100/104) of our MIBC samples by using RT-qPCR. Neuronal and luminal subtypes and low stromal gene expressions were associated with poor survival. In conclusion, we developed a robust and feasible method for the molecular subtyping according to the TCGA II, MDA, Lund and Consensus classifications. Our results suggest that stromal signatures have a superior prognostic value compared to tumor intrinsic signatures and therefore underline the importance of tumor-stroma interaction during the progression of MIBC.

Accuracy of Vital Signs Measurements by a Smartwatch and a Portable Health Device: Validation Study.

BACKGROUND: New consumer health devices are being developed to easily monitor multiple physiological parameters on a regular basis. Many of these vital sign measurement devices have yet to be formally studied in a clinical setting but have already spread widely throughout the consumer market. OBJECTIVE: The aim of this study was to investigate the accuracy and precision of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen saturation (SpO2) measurements of 2 novel all-in-one monitoring devices, the BodiMetrics Performance Monitor and the Everlast smartwatch. METHODS: We enrolled 127 patients (>18 years) from the Thomas Jefferson University Hospital Preadmission Testing Center. SBP and HR were measured by both investigational devices. In addition, the Everlast watch was utilized to measure DBP, and the BodiMetrics Performance Monitor was utilized to measure SpO2. After 5 min of quiet sitting, four hospital-grade standard and three investigational vital sign measurements were taken, with 60 seconds in between each measurement. The reference vital sign measurements were calculated by determining the average of the two standard measurements that bounded each investigational measurement. Using this method, we determined three comparison pairs for each investigational device in each subject. After excluding data from 42 individuals because of excessive variation in sequential standard measurements per prespecified dropping rules, data from 85 subjects were used for final analysis. RESULTS: Of 85 participants, 36 (42%) were women, and the mean age was 53 (SD 21) years. The accuracy guidelines were only met for the HR measurements in both devices. SBP measurements deviated 16.9 (SD 13.5) mm Hg and 5.3 (SD 4.7) mm Hg from the reference values for the Everlast and BodiMetrics devices, respectively. The mean absolute difference in DBP measurements for the Everlast smartwatch was 8.3 (SD 6.1) mm Hg. The mean absolute difference between BodiMetrics and reference SpO2 measurements was 3.02%. CONCLUSIONS: Both devices we investigated met accuracy guidelines for HR measurements, but they failed to meet the predefined accuracy guidelines for other vital sign measurements. Continued sale of consumer physiological monitors without prior validation and approval procedures is a public health concern.

The accuracy of blood pressure measurement by a smartwatch and a portable health device.

Objectives: Handheld medical devices and smartwatches that measure BP without a cuff have recently become available. Since these measurements are relatively more user-friendly than conventional cuff-based measurements they may aid in more frequent BP monitoring. We investigated the accuracy and precision of two popular cuff-less devices: the Everlast smartwatch and the BodiMetrics Performance Monitor.Methods: We enrolled 127 patients from the Thomas Jefferson University Hospital Preadmission Testing Center. Research staff were trained to measure BP according to manufacturer guidelines for the investigational devices. The Everlast smartwatch provides measurements of systolic (SBP) and diastolic (DBP) BP, whereas the Bodimetrics only provides SBP. Reference BP measurements were obtained using a hospital-grade automated sphygmomanometer. After 5 minutes of quiet sitting, four standard and three investigational BP measurements were taken with sixty seconds in between each measurement. The reference BP value was calculated by determining the average of the 2 standard BP measurements that bounded the investigational measurements. We thus determined 3 comparison pairs for each investigational device in each subject. We calculated the mean (SD) of the absolute difference between the respective investigational devices and the reference for SBP and DBP.Results: Data from 42 individuals was excluded because of variation in standard BP measurements per prespecified rules. Of 85 participants used for analysis, 36 (42%) were women, the mean (SD) age was 53 (21) years, 32 (38%) self-reported hypertension, and 97% of these (n = 31) reported taking antihypertensive medications. The average differences between the Everlast watch and reference were 16.9 (13.5) mm Hg for SBP and 8.3 (6.1) mm Hg for DBP. The average difference between the Bodimetrics performance monitor and the reference was 5.3 (4.7) mm Hg for SBP.Conclusions: The Everlast smartwatch and the BodiMetrics Performance Monitor we tested are not accurate enough to be used as BP measurement devices.

[Blood pressure measurement using pulse transit time]. / Bloeddrukmeting op basis van de polsgolf-transittijd.

Blood pressure has been measured with a cuff for over a 100 years. Recently, various devices and smart phone applications that measure blood pressure without a cuff using pulse transit time (PTT) have become available. These measurements are based on the inverse relationship between blood pressure and PTT. PTT constitutes the time delay between the QRS complex on ECG and the onset of a photoplethysmography pulse wave, for example in the finger. Since these measurements are relatively more user-friendly than conventional cuff-based measurements, they may aid in more frequent blood pressure monitoring by patients themselves. Initial validation studies, however, seem to suggest that blood pressure measurement using PTT is not accurate. Given the current pace of development in PTT-based blood pressure monitors it seems likely that physicians will be increasingly confronted with measurements from these devices. For the time being, it seems wise to not recommend these types of monitors to patients and to avoid using any of their measurements when making diagnostic or therapeutic decisions.