Assessing uterine electrophysiology prior to elective term induction of labor.

Objective: The purpose of this study was to determine if uterine electrophysiological signals gathered from 151 non-invasive biomagnetic sensors spread over the abdomen were associated with successful induction of labor (IOL). Study design: Uterine magnetomyogram (MMG) signals were collected using the SARA (SQUID Array for Reproductive Assessment) device from 33 subjects between 37 and 42 weeks gestational age. The signals were post-processed, uterine contractile related MMG bursts were detected, and parameters in the time and frequency domain were extracted. The modified Bishop score calculated at admission was used to determine the method of IOL. Wilcoxon's rank-sum test was used to compare IOL successes and failures for differences in gestational age (GA), parity, modified Bishop's score, maximum oxytocin, and electrophysiological parameters extracted from MMG. Results: The average parity was three times (3x) higher (1.53 versus 0.50; p = 0.039), and the average modified Bishop score was 2x higher (3.32 versus 1.63; p = 0.032) amongst IOL successes than failures, while the average GA and maximum oxytocin showed a small difference. For the MMG parameters, successful IOLs had, on average, 3.5x greater mean power during bursts (0.246 versus 0.070; p = 0.034) and approximately 1.2x greater mean number of bursts (2.05 versus 1.68; p = 0.036) compared to the failed IOLs, but non-significant differences were observed in mean peak frequency, mean burst duration, and mean duration between bursts. Conclusion: The study showed that inductions of labor that took less than 24 h to deliver have a higher mean power in the baseline electrophysiological activity of the uterus when recorded prior to planned induction. The results are indicative that baseline electrophysiological activity measured prior to induction is associated with successful induction.

IPW-5371 mitigates the delayed effects of acute radiation exposure in WAG/RijCmcr rats when started 15 days after PBI with bone marrow sparing.

PURPOSE: To test IPW-5371 for the mitigation of the delayed effects of acute radiation exposure (DEARE). Survivors of acute radiation exposure are at risk for developing delayed multi-organ toxicities; however, there are no FDA-approved medical countermeasures (MCM) to mitigate DEARE. METHODS: WAG/RijCmcr female rat model of partial-body irradiation (PBI), by shielding part of one hind leg, was used to test IPW-5371 (7 and 20 mg kg-1 d-1) for mitigation of lung and kidney DEARE when started 15 d after PBI. Rats were fed known amounts of IPW-5371 using a syringe, instead of delivery by daily oral gavage, sparing exacerbation of esophageal injury by radiation. The primary endpoint, all-cause morbidity was assessed over 215 d. Secondary endpoints: body weight, breathing rate and blood urea nitrogen were also assessed. RESULTS: IPW-5371 enhanced survival (primary endpoint) as well as attenuated secondary endpoints of lung and kidney injuries by radiation. CONCLUSION: To provide a window for dosimetry and triage, as well as avoid oral delivery during the acute radiation syndrome (ARS), the drug regimen was started at 15 d after 13.5 Gy PBI. The experimental design to test mitigation of DEARE was customized for translation in humans, using an animal model of radiation that was designed to simulate a radiologic attack or accident. The results support advanced development of IPW-5371 to mitigate lethal lung and kidney injuries after irradiation of multiple organs.

Delayed renal injury in survivors of hematologic acute radiation syndrome.

PURPOSE: A mass casualty disaster involving radiological or nuclear agents continues to be a public health concern which requires consideration of both acute and late tissue toxicities in exposed victims. With the advent of advanced treatment options for the mitigation of hematological injuries, there are likely to be survivors of total body irradiation (TBI) exposures as high as 8-10 Gy. These survivors are at risk for a range of delayed multi-organ morbidities including progressive renal failure. MATERIAL AND METHODS: Here, we established the WAG/RijCmcr rat as an effective model for the evaluation of medical countermeasures (MCM) for acute hematologic radiation syndrome (H-ARS). The LD50/30 dose for adult and pediatric WAG/RijCmcr rats was determined for both sexes. We then confirmed the FDA-approved MCM pegfilgrastim (peg-GCSF, Neulasta®) mitigates H-ARS in adult male and female rats. Finally, we evaluated survival and renal dysfunction up to 300 d post-TBI in male and female adult rats. RESULTS: In the WAG/RijCmcr rat model, 87.5% and 100% of adult rats succumb to lethal hematopoietic acute radiation syndrome (H-ARS) at TBI doses of 8 and 8.5 Gy, respectively. A single dose of the hematopoietic growth factor peg-GCSF administered at 24 h post-TBI improved survival during H-ARS. Peg-GCSF treatment improved 30 d survival from 12.5% to 83% at 8 Gy and from 0% to 63% at 8.5 Gy. We then followed survivors of H-ARS through day 300. Rats exposed to TBI doses greater than 8 Gy had a 26% reduction in survival over days 30-300 compared to rats exposed to 7.75 Gy TBI. Concurrent with the reduction in long-term survival, a dose-dependent impairment of renal function as assessed by blood urea nitrogen (BUN) and urine protein to urine creatinine ratio (UP:UC) was observed. CONCLUSION: Together, these data show survivors of H-ARS are at risk for the development of delayed renal toxicity and emphasize the need for the development of medical countermeasures for delayed renal injury.

Mitigation of Multi-Organ Radiation Injury with ACE2 Agonist Diminazene Aceturate.

The renin-angiotensin system (RAS) is known to regulate the pathogenesis of radiation-induced injury as inhibitors of the RAS enzyme angiotensin converting enzyme (ACE) have established function as mitigators of multi-organ radiation injury. To further elucidate the role of RAS signaling during both the acute and delayed syndromes of radiation exposure, we have evaluated whether pharmacologic modulation of alternate RAS enzyme angiotensin converting enzyme 2 (ACE2) reduces the pathogenesis of multi-organ radiation-induced injuries. Here, we demonstrate pharmacologic ACE2 activation with the small molecule ACE2 agonist diminazene aceturate (DIZE) improves survival in rat models of both hematologic acute radiation syndrome (H-ARS) and multi-organ delayed effects of acute radiation exposure (DEARE). In the H-ARS model, DIZE treatment increased 30-day survival by 30% compared to vehicle control rats after a LD50/30 total-body irradiation (TBI) dose of 7.75 Gy. In the mitigation of DEARE, ACE2 agonism with DIZE increased median survival by 30 days, reduced breathing rate, and reduced blood urea nitrogen (BUN) levels compared to control rats after partial-body irradiation (PBI) of 13.5 Gy. DIZE treatment was observed to have systemic effects which may explain the multi-organ benefits observed including mobilization of hematopoietic progenitors to the circulation and a reduction in plasma TGF-beta levels. These data suggest the ACE2 enzyme plays a critical role in the RAS-mediated pathogenesis of radiation injury and may be a potential therapeutic target for the development of medical countermeasures for acute radiation exposure.

Critical Information from High Fidelity Arterial and Venous Pressure Waveforms During Anesthesia and Hemorrhage.

PURPOSE: Peripheral venous pressure (PVP) waveform analysis is a novel, minimally invasive, and inexpensive method of measuring intravascular volume changes. A porcine cohort was studied to determine how venous and arterial pressure waveforms change due to inhaled and infused anesthetics and acute hemorrhage. METHODS: Venous and arterial pressure waveforms were continuously collected, while each pig was under general anesthesia, by inserting Millar catheters into a neighboring peripheral artery and vein. The anesthetic was varied from inhaled to infused, then the pig underwent a controlled hemorrhage. Pearson correlation coefficients between the power of the venous and arterial pressure waveforms at each pig's heart rate frequency were calculated for each variation in the anesthetic, as well as before and after hemorrhage. An analysis of variance (ANOVA) test was computed to determine the significance in changes of the venous pressure waveform means caused by each variation. RESULTS: The Pearson correlation coefficients between venous and arterial waveforms decreased as anesthetic dosage increased. In an opposing fashion, the correlation coefficients increased as hemorrhage occurred. CONCLUSION: Anesthetics and hemorrhage alter venous pressure waveforms in distinctly different ways, making it critical for researchers and clinicians to consider these confounding variables when utilizing pressure waveforms. Further work needs to be done to determine how best to integrate PVP waveforms into clinical decision-making.

Pharmacologic ACE-Inhibition Mitigates Radiation-Induced Pneumonitis by Suppressing ACE-Expressing Lung Myeloid Cells.

PURPOSE: Radiation-induced lung injury is a major dose-limiting toxicity for thoracic radiation therapy patients. In experimental models, treatment with angiotensin converting enzyme (ACE) inhibitors mitigates radiation pneumonitis; however, the mechanism of action is not well understood. Here, we evaluate the direct role of ACE inhibition on lung immune cells. METHODS AND MATERIALS: ACE expression and activity were determined in the lung immune cell compartment of irradiated adult rats after either high dose fractionated radiation therapy to the right lung (5 fractions × 9 Gy) or a single dose of 13.5 Gy partial body irradiation. Mitigation of radiation-induced pneumonitis with the ACE-inhibitor lisinopril was evaluated in the 13.5 Gy rat partial body irradiation model. During pneumonitis, we characterized inflammation and immune cell content in the lungs and bronchoalveolar lavage fluid. In vitro mechanistic studies were performed using primary human monocytes and the human monocytic THP-1 cell line. RESULTS: In both the partial body irradiation and fractionated radiation therapy models, radiation increased ACE activity in lung immune cells. Treatment with lisinopril improved survival during radiation pneumonitis (P = .0004). Lisinopril abrogated radiation-induced increases in bronchoalveolar lavage fluid monocyte chemoattractant protein 1 (chemokine ligand 2) and MIP-1a cytokine levels (P < .0001). Treatment with lisinopril reduced both ACE expression (P = .006) and frequency of CD45+ CD11b+ lung myeloid cells (P = .004). In vitro, radiation injury acutely increased ACE activity (P = .045) and reactive oxygen species (ROS) generation (P = .004) in human monocytes, whereas treatment with lisinopril blocked radiation-induced increases in both ACE and ROS. Radiation-induced ROS generation was blocked by pharmacologic inhibition of either NADPH oxidase 2 (P = .012) or the type 1 angiotensin receptor (P = .013). CONCLUSIONS: These data demonstrate radiation-induced ACE activation within the immune compartment promotes the pathogenesis of radiation pneumonitis, while ACE inhibition suppresses activation of proinflammatory immune cell subsets. Mechanistically, our in vitro data demonstrate radiation directly activates the ACE/type 1 angiotensin receptor pathway in immune cells and promotes generation of ROS via NADPH oxidase 2.

Gardening for Health: Using Garden Coordinators and Volunteers to Implement Rural School and Community Gardens.

Gardens provide access to healthy food, increase access to nutrition and physical activity opportunities, and are a focal point for community interventions. We used a gardening intervention to improve local access to and consumption of fruits and vegetables and as an integral part of overall efforts of local wellness coalitions. Seasonal garden coordinators were hired, and action plans included goals for nutrition and physical activity education programs and youth and adult engagement. The characteristics of each garden (size, items planted, number of volunteers) and pre- and post-intervention surveys were used to understand how the gardens affected communities. Thirteen gardens were planted, and volunteers provided 18,136 hours; adults from the community reported an increased awareness of garden benefits. The community garden intervention provided opportunities for collaboration with a variety of schools, community organizations, and city and tribal organizations, thereby increasing the sustainability of the intervention.

Impact of Hurricane Sandy on hospital emergency and dialysis services: a retrospective survey.

OBJECTIVE: Hurricane Sandy forced closures of many free-standing dialysis centers in New York City in 2012. Hemodialysis (HD) patients therefore sought dialysis treatments from nearby hospitals. The surge capacity of hospital dialysis services was the rate-limiting step for streamlining the emergency department flow of HD patients. The aim of this study was to determine the extent of the HD patients surge and to explore difficulties encountered by hospitals in Brooklyn, New York (USA) due to Hurricane Sandy. METHODS: A retrospective survey on hospital dialysis services was conducted by interviewing dialysis unit managers, focusing on the influx of HD patients from closed dialysis centers to hospitals, coping strategies these hospitals used, and difficulties encountered. RESULTS: In total, 347 HD patients presented to 15 Brooklyn hospitals for dialysis. The number of transient HD patients peaked two days after landfall and gradually decreased over a week. Hospital dialysis services reported issues with lack of dialysis documentation from transient dialysis patients (92.3%), staff shortage (50%), staff transportation (71.4%), and communication with other agencies (53.3%). Linear regression showed that factors significantly associated with enhanced surge capacity were the size of inpatient dialysis unit (P = .040), having affiliated outpatient dialysis centers (P = .032), using extra dialysis machines (P = .014), and having extra workforce (P = .007). Early emergency plan activation (P = .289) and shortening treatment time (P = .118) did not impact the surge capacity significantly in this study. CONCLUSION: These findings provide potential improvement options for receiving hospitals dialysis units to prepare for future events.

Waterworks, a full-scale chemical exposure exercise: interrogating pediatric critical care surge capacity in an inner-city tertiary care medical center.

INTRODUCTION: Pediatric Intensive Care Unit (PICU) resources are overwhelmed in disaster as the need to accommodate influx of critically-ill children is increased. A full-scale chlorine overexposure exercise was conducted by the New York Institute for All Hazard Preparedness (NYIAHP) to assess the appropriateness of response of Kings County Hospital Center's (KCHC's) PICU surge plan to an influx of critically-ill children. The primary endpoint that was assessed was the ability of the institution to follow the PICU surge plan, while secondary endpoints include the ability to provide appropriate medical management. METHODS: Thirty-six actors/patients (medical students or emergency medicine residents) were educated on presentations and appropriate medical management of patients after a chlorine overexposure, as well as lectures on drill design and expected PICU surge response. Victims presented to the hospital after simulated accidental chlorine overexposure at a public pool. Twenty-two patients with 14 family members needed evaluation; nine of these patients would require PICU admission. Three of nine PICU patients were low-fidelity mannequins. In addition to the 36 actor/patient evaluators, each area had two to four expert evaluators (disaster preparedness experts) to assess appropriateness of global response. Patients were expected to receive standard of care. Appropriateness of medical decisions and treatment was assessed retrospectively with review of electronic medical record. RESULTS: The initial PICU census was three of seven; two of these patients were transferred to the general ward. Of the nine patients that required Intensive Care Unit (ICU) admission, six actor/patients were admitted to the PICU, one was admitted to the Surgical Intensive Care Unit (SICU), one went to the Operating Room (OR), and one was admitted to a monitored-surge general pediatric bed. The remaining 13 actor/patients were treated and released. Medical, nursing, and respiratory staffing in the PICU and the general ward were increased by two main mechanisms (extension of work hours and in-house recruitment of additional staff). Emergency Department (ED) staffing was artificially increased prior to the drill. With the exception of ocular fluid pH testing in patients with ocular pruritus, all necessary treatments were given; however, an unneeded albuterol treatment was administered to one patient. Chart review showed adequate discharge instructions in four of 13 patients. Nine patients without respiratory complaints in the ED were not instructed to observe for dyspnea. All patients were in the PICU or alternate locations within 90 minutes. Discussion The staff was well versed in the major details of KCHC's PICU surge plan, which allowed smooth transition of patient care from the ED to the PICU. The plan provided for a roadmap to achieve adequate medical, nursing, and respiratory therapists. Medical therapy was appropriate in the PICU; however, in the ED, patients with ocular complaints did not receive optimal care. In addition, written discharge instruction and educational material regarding chlorine overexposure to all patients were not consistently provided. The PICU surge plan was immediately accessible through the KCHC intranet; however, not all participants were cognizant of this fact; this decreased the efficiency with which the roadmap was followed. An exaggerated ED staff facilitated evaluation and transfer of patients. CONCLUSION: During disasters, the ability to surge is paramount and each hospital addresses it differently. Hospitals and departments have written surge plans, but there is no literature available which assesses the validity of said plans through a rigorous, structured, simulated disaster drill. This study is the first to assess validity and effectiveness of a hospital's PICU surge plan. Overall, the KCHC PICU surge plan was effective; however, several deficiencies (mainly in communication and patient education in the ED) were identified, and this will improve future response.

Clinical characteristics of aortic aneurysm and dissection as a cause of sudden death in outpatients.

OBJECTIVE: To describe characteristics of nonhospitalized patients experiencing sudden death from aortic causes and compare with characteristics of patients experiencing nontraumatic, unexpected, outpatient death from other causes. METHODS: Retrospective case-control analysis of patients aged 18 to 65 years with nontraumatic, unexpected, outpatient cardiac arrest, emergency department (ED) resuscitation attempts, and autopsy-determined cause of death. Demographics, prodromal symptoms, and arrest characteristics were examined, and univariate comparisons between patients with aortic and those with nonaortic causes of death were performed. RESULTS: A total of 384 patients met inclusion criteria. Aortic pathology represented 4.4% of patients (12 dissections, 5 aneurysms). Preexisting aortic disease (n = 2) and antemortem suspicion of an aortic cause (n = 3) were uncommon. Patients with an aortic cause of death often had prodromal symptoms (53% 95% CI; 28%-77%) and hemopericardium (47% 95% CI; 23%-72%), were older, and were more likely to have a pulse in the ED, an arrest rhythm of pulseless electrical activity, and an arrest witnessed arrest by a medical provider. CONCLUSION: In this sample of outpatients with cardiac arrest from aortic disease, death was not instantaneous, and hemopericardium was common in many patients with dissection.

Early radiation-induced lung injury in a patient with prior diagnosis of bronchiolitis obliterans organizing pneumonitis.

This case study is to report the observation that clinically diagnosed radiation pneumonitis (geometrically conforming to the radiation treatment volume) occurred at a subthreshold radiation dose in a patient with a previous history of pathologically diagnosed bronchiolitis obliterans organizing pneumonitis.