The hemodynamic effects of ventricular pacing with and without atrioventricular synchrony in patients with normal and diminished left ventricular function

The relative hemodynamic effects of heart rate, inotropic state, and atrioventricular (AV) synchrony during ventricular pacing were evaluated in 10 patients with normal left ventricular ejection fraction (LVEF) (0.66 +/- 0.07, mean S.D.) and in eight patients with a diminished LVEF (0.34 +/- 0.18). Hemodynamics were measured at AV intervals of 130, 0, and -130 msec during ventricular pacing at a baseline rate that was 10 pulses/min greater than the resting heart rate, at 130 pulses/min alone, and at 130 pulses/min during continuous intravenous infusion of dobutamine. During baseline ventricular pacing and during ventricular pacing at 130 pulses/min with and without dobutamine, both groups of patients had a significant decrease in cardiac index, stroke volume index, and stroke work index when the AV pacing interval was decreased from 130 to 0 msec. The observed decrease in these three hemodynamic variables was similar when patients with diminished LVEF were compared to patients with normal LVEF. No further significant decrease in cardiac index, stroke volume index, and stroke work index occurred in either group when the AV interval was changed from 0 to -130 msec during baseline ventricular pacing or during ventricular pacing at 130 with and without dobutamine. Beneficial hemodynamic effects occur during ventricular pacing when AV synchrony is maintained at resting heart rates and during increases in heart rate and inotropic state in patients with normal and diminished LVEF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26988/1/0000555.pd

An Analysis on the Detection of Biological Contaminants Aboard Aircraft

The spread of infectious disease via commercial airliner travel is a significant and realistic threat. To shed some light on the feasibility of detecting airborne pathogens, a sensor integration study has been conducted and computational investigations of contaminant transport in an aircraft cabin have been performed. Our study took into consideration sensor sensitivity as well as the time-to-answer, size, weight and the power of best available commercial off-the-shelf (COTS) devices. We conducted computational fluid dynamics simulations to investigate three types of scenarios: (1) nominal breathing (up to 20 breaths per minute) and coughing (20 times per hour); (2) nominal breathing and sneezing (4 times per hour); and (3) nominal breathing only. Each scenario was implemented with one or seven infectious passengers expelling air and sneezes or coughs at the stated frequencies. Scenario 2 was implemented with two additional cases in which one infectious passenger expelled 20 and 50 sneezes per hour, respectively. All computations were based on 90 minutes of sampling using specifications from a COTS aerosol collector and biosensor. Only biosensors that could provide an answer in under 20 minutes without any manual preparation steps were included. The principal finding was that the steady-state bacteria concentrations in aircraft would be high enough to be detected in the case where seven infectious passengers are exhaling under scenarios 1 and 2 and where one infectious passenger is actively exhaling in scenario 2. Breathing alone failed to generate sufficient bacterial particles for detection, and none of the scenarios generated sufficient viral particles for detection to be feasible. These results suggest that more sensitive sensors than the COTS devices currently available and/or sampling of individual passengers would be needed for the detection of bacteria and viruses in aircraft

Radiation Combined With Thermal Injury Induces Immature Myeloid Cells

The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sub-lethal ionization radiation exposure combined with a full thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a 20% total body surface area (TBSA) full-thickness contact burn or sham procedure followed by a single whole body dose of 5-Gy radiation. Serum, spleen and peripheral lymph nodes were harvested at 3 and 14 days post-injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated pro- and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but was significantly elevated after burn alone and RCI at 14 days post-injury. In contrast to the T-cell suppressive nature of myeloid-derived suppressor cells (MDSC) found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in IFN-γ and a decrease in IL-10. This is consistent with previous work in burn injury indicating that a MDSC-like population increases innate immunity. RCI results in the increase of distinct populations of Gr-1(+) CD11b(+)cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host

Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial

BACKGROUND: VEGF and VEGF receptor 2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether the addition of ramucirumab, a VEGFR-2 antagonist monoclonal antibody, to first-line chemotherapy improves outcomes in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma. METHODS: For this double-blind, randomised, placebo-controlled, phase 3 trial done at 126 centres in 20 countries, we recruited patients aged 18 years or older with metastatic, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. Eligible patients were randomly assigned (1:1) with an interactive web response system to receive cisplatin (80 mg/m2, on the first day) plus capecitabine (1000 mg/m2, twice daily for 14 days), every 21 days, and either ramucirumab (8 mg/kg) or placebo on days 1 and 8, every 21 days. 5-Fluorouracil (800 mg/m2 intravenous infusion on days 1-5) was permitted in patients unable to take capecitabine. The primary endpoint was investigator-assessed progression-free survival, analysed by intention to treat in the first 508 patients. We did a sensitivity analysis of the primary endpoint, including a central review of CT scans. Overall survival was a key secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT02314117. FINDINGS: Between Jan 28, 2015, and Sept 16, 2016, 645 patients were randomly assigned to receive ramucirumab plus fluoropyrimidine and cisplatin (n=326) or placebo plus fluoropyrimidine and cisplatin (n=319). Investigator-assessed progression-free survival was significantly longer in the ramucirumab group than the placebo group (hazard ratio [HR] 0·753, 95% CI 0·607-0·935, p=0·0106; median progression-free survival 5·7 months [5·5-6·5] vs 5·4 months [4·5-5·7]). A sensitivity analysis based on central independent review of the radiological images did not corroborate the investigator-assessed difference in progression-free survival (HR 0·961, 95% CI 0·768-1·203, p=0·74). There was no difference in overall survival between groups (0·962, 0·801-1·156, p=0·6757; median overall survival 11·2 months [9·9-11·9] in the ramucirumab group vs 10·7 months [9·5-11·9] in the placebo group). The most common grade 3-4 adverse events were neutropenia (85 [26%] of 323 patients in the ramucirumab group vs 85 [27%] of 315 in the placebo group), anaemia (39 [12%] vs 44 [14%]), and hypertension (32 [10%] vs 5 [2%]). The incidence of any-grade serious adverse events was 160 (50%) of 323 patients in the ramucirumab group and 149 (47%) of 315 patients in the placebo group. The most common serious adverse events were vomiting (14 [4%] in the ramucirumab group vs 21 [7%] in the placebo group) and diarrhoea (11 [3%] vs 19 [6%]). There were seven deaths in each group, either during study treatment or within 30 days of discontinuing study treatment, which were the result of treatment-related adverse events. In the ramucirumab group, these adverse events were acute kidney injury, cardiac arrest, gastric haemorrhage, peritonitis, pneumothorax, septic shock, and sudden death (n=1 of each). In the placebo group, these adverse events were cerebrovascular accident (n=1), multiple organ dysfunction syndrome (n=2), pulmonary embolism (n=2), sepsis (n=1), and small intestine perforation (n=1). INTERPRETATION: Although the primary analysis for progression-free survival was statistically significant, this outcome was not confirmed in a sensitivity analysis of progression-free survival by central independent review, and did not improve overall survival. Therefore, the addition of ramucirumab to cisplatin plus fluoropyrimidine chemotherapy is not recommended as first-line treatment for this patient population. FUNDING: Eli Lilly and Company.status: publishe