Behavior of glioblastoma brain tumor stem cells following a suborbital rocket flight: reaching the "edge" of outer space.

The emerging arena of space exploration has created opportunities to study cancer cell biology in the environments of microgravity and hypergravity. Studying cellular behavior in altered gravity conditions has allowed researchers to make observations of cell function that would otherwise remain unnoticed. The patient-derived QNS108 brain tumor initiating cell line (BTIC), isolated from glioblastoma (GBM) tissue, was launched on a suborbital, parabolic rocket flight conducted by EXOS Aerospace Systems & Technologies. All biologicals and appropriate ground controls were secured post-launch and transported back to our research facility. Cells from the rocket-flight and ground-based controls were isolated from the culture containers and expanded on adherent flasks for two weeks. In vitro migration, proliferation, and stemness assays were performed. Following cell expansion, male nude mice were intracranially injected with either ground-control (GC) or rocket-flight (RF) exposed cells to assess tumorigenic capacity (n = 5 per group). Patient-derived QNS108 BTICs exposed to RF displayed more aggressive tumor growth than the GC cells in vitro and in vivo. RF cells showed significantly higher migration (p < 0.0000) and stemness profiles (p < 0.01) when compared to GC cells. Further, RF cells, when implanted in vivo in the brain of rodents had larger tumor-associated cystic growth areas (p = 0.00029) and decreased survival (p = 0.0172) as compared to those animals that had GC cells implanted.

Real versus simulated galactic cosmic radiation for investigating cancer risk in the hematopoietic system - are we comparing apples to apples?

Deep space exploration missions need strategies to mitigate the potentially harmful exposure to galactic cosmic radiation. This form of radiation can cause significant damage to biological systems and organisms, which include radiation-induced carcinogenesis in the hematopoietic system. Ongoing studies investigate these effects using cell- and animal-based studies in low earth orbit. The logistic challenges and costs involved with sending biological specimens to space have prompted the development of surrogate ground-based radiation experiments to study the mechanisms of biological injury and cancer risk. However, simulating galactic cosmic radiation has proven difficult and current studies are only partially succeeding at replicating the complexity of this radiation and its downstream injury pathways. Accurate simulation of chronic, low dose galactic radiation will improve our ability to test mitigation strategies such as drug development and improved shielding materials that could be crucial and essential for successful space exploration.

Reducing chest radiography utilization in the medical intensive care unit.

BACKGROUND AND PURPOSE: Daily chest radiographs (CXRs) have long been a routine part of care. However, evidence as well as changing technology has promoted on-demand CXRs as beneficial to patient care. We found that a substantial number of routine daily CXRs were being ordered, with some of the orders staying active even after extubation. METHODS: Within a 19-bed adult medical ICU, we prospectively utilized 3 intervention phases from October 1, 2014, to February 28, 2018, to reduce routine CXRs. Nurse Practitioners (NP) initiated this quality improvement (QI) project, aiming to reduce the number of unnecessary of CXRs. Interventions included staff survey, routine CXR order removal, duplicate alerts, visual reminders, and an electronic clinical decision support tool. Monthly education of appropriate CXRs and bedside ultrasound were facilitated by NPs. The outcome measures of interest include: the number of CXRs per patient-day, the number of routine and on-demand CXRs, mortality rate, ICU length of stay, and ventilator days, radiation and cost. CONCLUSIONS: Total number of CXRs per patient-day decreased by 36.1%. The proportion of routine CXRs decreased from 55.37% to 13.18%; on-demand orders increased, from 44.63% to 86.82%; and calculated radiation-exposure per census decreased, from 0.011 to 0.008 mSv. In addition, charges to patients for CXRs decreased by $7,750/month. ICU mortality and ventilator days per census remained stable. IMPLICATIONS FOR PRACTICE: By an orchestrated process that included creating awareness and desire to change CXR ordering practices, we were able to decrease routine CXRs and increase on-demand utilization while maintaining counterbalance measures.

A novel semiquantitative assessment of right ventricular systolic function with a modified subcostal echocardiographic view.

OBJECTIVES: The tricuspid annular plane systolic excursion (TAPSE) is a validated measure of right ventricular function; however, the apical echocardiographic window varies and has limitations in intensive care unit (ICU) patients receiving mechanical ventilation or those with underlying disease and air entrapment. We aimed to evaluate the subcostal echocardiographic assessment of tricuspid annular kick (SEATAK) as an alternative to TAPSE in critically ill patients. METHODS: To measure SEATAK, we obtained the subcostal inferior vena cava view and used M-mode to measure excursion of the tricuspid annulus (kick). Analysis was performed with JMP for Bland-Altman and Spearman correlations. RESULTS: We evaluated 45 patients, 26 (57.8%) of whom were women, with a mean age of 60.8 years. We were not able to obtain the apical view to measure TAPSE in 8.9% of the patients. In contrast, SEATAK was measured in all patients. The mean SEATAK and TAPSE were 1.62 cm and 1.93 cm, respectively, with a mean pairwise difference of -0.26 cm (95% CI: -0.19 to -0.35), with the SEATAK value being lower than TAPSE. The overall correlation was strong and significant (ρ = .86, P=.03). The graphical correlation was maintained between TAPSE and SEATAK and the degree of RVF. CONCLUSION: In patients presenting with RVF in the ICU (or in situations where the apical echocardiographic view is suboptimal for tricuspid annular assessment), SEATAK can be an alternative to TAPSE. Further research is needed to validate and determine the sensitivity and specificity of SEATAK for RVF prognostication.

Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients Treated with Therapeutic Hypothermia.

Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p = 0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved.

Cardiac arrest in a 21-year-old man after ingestion of 1,3-DMAA-containing workout supplement.

Dietary supplements containing 1,3-dimethylamylamine (DMAA) have been determined to be illegal by the Food and Drug Administration (FDA); although banned, the products are still widely available for purchase. Adverse effects reported include cardiac arrest, hemorrhagic stroke, and death. Nonetheless, such products remain popular among young people because of advertised claims of exercise performance enhancement and fat burning. We describe a case of a young man who took such a supplement and suffered a cardiac arrest. Notably, the product consumed was not on the FDA list of substances containing DMAA. This case highlights the importance for clinicians to be aware of the potential harm of the DMAA-containing products by maintaining a high index of suspicion in otherwise healthy individuals presenting with cardiac arrest. It is of particular importance to sports medicine physicians who are most involved in education and counseling of patients potentially at risk of taking such products.

Noninvasive assessment of right heart function and hemodynamics during exercise in patients with pulmonary arterial hypertension.

OBJECTIVES: Noninvasive assessment of right heart function and hemodynamics in patients with pulmonary arterial hypertension (PAH) is most often performed at rest, whereas the symptoms, in general, present with exertion. Assessment during exertion is limited to symptom assessment and the 6-minute walk distance. We investigated the feasibility of obtaining echocardiographic data that could accurately reflect pulmonary artery pressures (PAP), particularly mean PAP and right ventricular function during exercise in patients with PAH. METHODS: We investigated right ventricular function and hemodynamics using echocardiography during symptom-limited exercise in 10 consecutive patients undergoing right heart catheterization (RHC) as part of their clinical evaluation for PAH. We further assessed these measurements for correlation with known predictors of outcome in PAH in an exploratory analysis. RESULTS: We were able to successfully obtain complete right heart measurements by echocardiography, including mean PAP, in the majority (9 of 10) of the subjects. One patient had an incomplete tricuspid regurgitation jet at rest and with exercise. Echocardiographic pulmonary vascular resistance correlated with RHC cardiac output and brain natriuretic peptide level, whereas tricuspid annular plane systolic excursion during exercise correlated with right atrial pressure on RHC, brain natriuretic peptide, and 6-minute walk distance. Tricuspid regurgitation velocity and mean PAP with exercise correlated moderately with mean PAP and cardiac output by RHC. CONCLUSIONS: Exercise echocardiography can provide meaningful data in patients with PAH, including measuring mean PAP. The presence of correlations in this small number of patients indicates promising targets for future investigation.