Peripheral skin cooling during hyper-gravity: hemodynamic reactions.

Introduction: Orthostatic dysregulation occurs during exposure to an increased gravitational vector and is especially common upon re-entering standard Earth gravity (1 g) after an extended period in microgravity (0 g). External peripheral skin cooling (PSC) has recently been described as a potent countermeasure against orthostatic dysregulation during heat stress and in lower body negative pressure (LBNP) studies. We therefore hypothesized that PSC may also be an effective countermeasure during hyper-gravity exposure (+Gz). Methods: To investigate this, we designed a randomized short-arm human centrifuge (SAHC) experiment ("Coolspin") to investigate whether PSC could act as a stabilizing factor in cardiovascular function during +Gz. Artificial gravity between +1 g and +4 g was generated by a SAHC. 18 healthy male volunteers completed two runs in the SAHC. PSC was applied during one of the two runs and the other run was conducted without cooling. Each run consisted of a 10-min baseline trial followed by a +Gz step protocol marked by increasing g-forces, with each step being 3 min long. The following parameters were measured: blood pressure (BP), heart rate (HR), stroke volume (SV), total peripheral resistance (TPR), cardiac output (CO). Furthermore, a cumulative stress index for each subject was calculated. Results: +Gz led to significant changes in primary as well as in secondary outcome parameters such as HR, SV, TPR, CO, and BP. However, none of the primary outcome parameters (HR, cumulative stress-index, BP) nor secondary outcome parameters (SV, TPR, CO) showed any significant differences-whether the subject was cooled or not cooled. Systolic BP did, however, tend to be higher amongst the PSC group. Conclusion: In conclusion, PSC during +Gz did not confer any significant impact on hemodynamic activity or orthostatic stability during +Gz. This may be due to lower PSC responsiveness of the test subjects, or an insufficient level of body surface area used for cooling. Further investigations are warranted in order to comprehensively pinpoint the exact degree of PSC needed to serve as a useful countermeasure system during +Gz.

Feasibility and outcome of reproducible clinical interpretation of high-dimensional molecular data: a comparison of two molecular tumor boards.

BACKGROUND: Structured and harmonized implementation of molecular tumor boards (MTB) for the clinical interpretation of molecular data presents a current challenge for precision oncology. Heterogeneity in the interpretation of molecular data was shown for patients even with a limited number of molecular alterations. Integration of high-dimensional molecular data, including RNA- (RNA-Seq) and whole-exome sequencing (WES), is expected to further complicate clinical application. To analyze challenges for MTB harmonization based on complex molecular datasets, we retrospectively compared clinical interpretation of WES and RNA-Seq data by two independent molecular tumor boards. METHODS: High-dimensional molecular cancer profiling including WES and RNA-Seq was performed for patients with advanced solid tumors, no available standard therapy, ECOG performance status of 0-1, and available fresh-frozen tissue within the DKTK-MASTER Program from 2016 to 2018. Identical molecular profiling data of 40 patients were independently discussed by two molecular tumor boards (MTB) after prior annotation by specialized physicians, following independent, but similar workflows. Identified biomarkers and resulting treatment options were compared between the MTBs and patients were followed up clinically. RESULTS: A median of 309 molecular aberrations from WES and RNA-Seq (n = 38) and 82 molecular aberrations from WES only (n = 3) were considered for clinical interpretation for 40 patients (one patient sequenced twice). A median of 3 and 2 targeted treatment options were identified per patient, respectively. Most treatment options were identified for receptor tyrosine kinase, PARP, and mTOR inhibitors, as well as immunotherapy. The mean overlap coefficient between both MTB was 66%. Highest agreement rates were observed with the interpretation of single nucleotide variants, clinical evidence levels 1 and 2, and monotherapy whereas the interpretation of gene expression changes, preclinical evidence levels 3 and 4, and combination therapy yielded lower agreement rates. Patients receiving treatment following concordant MTB recommendations had significantly longer overall survival than patients receiving treatment following discrepant recommendations or physician's choice. CONCLUSIONS: Reproducible clinical interpretation of high-dimensional molecular data is feasible and agreement rates are encouraging, when compared to previous reports. The interpretation of molecular aberrations beyond single nucleotide variants and preclinically validated biomarkers as well as combination therapies were identified as additional difficulties for ongoing harmonization efforts.

Measuring Core Body Temperature Using a Non-invasive, Disposable Double-Sensor During Targeted Temperature Management in Post-cardiac Arrest Patients.

Background: Precisely measuring the core body temperature during targeted temperature management after return of spontaneous circulation is mandatory, as deviations from the recommended temperature might result in side effects such as electrolyte imbalances or infections. However, previous methods are invasive and lack easy handling. A disposable, non-invasive temperature sensor using the heat flux approach (Double Sensor), was tested against the standard method: an esophagus thermometer. Methods: The sensor was placed on the forehead of adult patients (n = 25, M/F, median age 61 years) with return of spontaneous circulation after cardiac arrest undergoing targeted temperature management. The recorded temperatures were compared to the established measurement method of an esophageal thermometer. A paired t-test was performed to examine differences between methods. A Bland-Altman-Plot and the intraclass correlation coefficient were used to assess agreement and reliability. To rule out possible influence on measurements, the patients' medication was recorded as well. Results: Over the span of 1 year and 3 months, data from 25 patients were recorded. The t-test showed no significant difference between the two measuring methods (t = 1.47, p = 0.14, n = 1,319). Bland-Altman results showed a mean bias of 0.02°C (95% confidence interval 0.00-0.04) and 95% limits of agreement of -1.023°C and 1.066°C. The intraclass correlation coefficient was 0.94. No skin irritation or allergic reaction was observed where the sensor was placed. In six patients the bias differed noticeably from the rest of the participants, but no sex-based or ethnicity-based differences could be identified. Influences on the measurements of the Double Sensor by drugs administered could also be ruled out. Conclusions: This study could demonstrate that measuring the core body temperature with the non-invasive, disposable sensor shows excellent reliability during targeted temperature management after survived cardiac arrest. Nonetheless, clinical research concerning the implementation of the sensor in other fields of application should be supported, as well as verifying our results by a larger patient cohort to possibly improve the limits of agreement.