Survival of Out-of-Hospital Pediatric Blunt Traumatic Arrest With Full Neurologic Recovery: Case Report.

We present the case of a 10-year-old previously healthy male who suffered an out-of-hospital cardiac arrest because of abdominal trauma and survived with excellent neurologic outcomes and near complete return to baseline functional status at hospital discharge. The rapid response and efficient mobilization of resources led to an excellent patient outcome despite the severity of injuries, including intra-abdominal injuries with expected mortality, out-of-hospital traumatic arrest, coagulopathy, and an extended pediatric intensive care unit stay. This case underscores the significance of timely advanced trauma life support interventions, especially early blood product administration, efficient transport, and airway management, while sharing a remarkable case of out-of-hospital pediatric traumatic arrest with near full recovery.

Physiological Effects of a Spit Restraint Device Saturated With Artificial Saliva.

BACKGROUND: Spit restraint devices, also referred to as spit hoods, spit masks, or spit socks, are used by law enforcement and medical personnel to minimize transmission of communicable disease from bodily fluids from agitated individuals. Several lawsuits have implicated spit restraint devices as contributing to the death of individuals who are physically restrained by means of asphyxiation due to saturation of the mesh restraint device with saliva. OBJECTIVES: This study aims to evaluate whether a saturated spit restraint device has any clinically significant effects on the ventilatory or circulatory parameters of healthy adult subjects. METHODS: Subjects wore a spit restraint device dampened with 0.5% carboxymethylcellulose, an artificial saliva. Baseline vitals were taken, and a wet spit restraint device was then placed over the subject's head, and repeat measurements were taken at 10, 20, 30, and 45 min. A second spit restraint device was placed 15 min after the first. Measurements at 10, 20, 30, and 45 min were compared with baseline using paired t-tests. RESULTS: The mean age of 10 subjects was 33.8 years, and 50% were female. There was no significant difference between baseline and while wearing the spit sock for 10, 20, 30, and 45 min for the measured parameters including heart rate, oxygen saturation, end-tidal CO2, respiratory rate, or blood pressure. No subject indicated respiratory distress or had to terminate the study. CONCLUSIONS: In healthy adult subjects, there were no statistically or clinically significant differences in ventilatory or circulatory parameters while wearing the saturated spit restraint.

Evaluation of the ventilatory effects on human subjects in prolonged hip-flexed/head-down restraint position.

BACKGROUND: The restraint chair is a tool used by law enforcement and correction personnel to control aggressive, agitated individuals. When initiating its use, subjects are often placed in a hip-flexed/head-down (HFHD) position to remove handcuffs. Usually, this period of time is less than two minutes but can become more prolonged in particularly agitated patients. Some have proposed this positioning limits ventilation and can result in asphyxia. The aim of this study is to evaluate if a prolonged HFHD restraint position causes significant ventilatory compromise. METHODS: Subjects exercised on a stationary bicycle until they reached 85% of their predicted maximal heart rate. They were then handcuffed with their hands behind their back and placed into a HFHD seated position for five minutes. The primary outcome measurement was maximal voluntary ventilation (MVV). This was measured at baseline, after initial placement into the HFHD position, and after five minutes of being in the position while still maintaining the HFHD position. Baseline measurements were compared with final measurements for statistically significant differences. RESULTS: We analyzed data for 15 subjects. Subjects had a mean MVV of 165.3 L/min at baseline, 157.8 L/min after initially being placed into the HFHD position, and a mean of 138.7 L/min after 5 min in the position. The mean baseline % predicted MVV was 115%; after 5 min in the HFHD position the mean was 96%. This 19% absolute difference was statistically significant (p = 0.001). CONCLUSIONS: In healthy seated male subjects with recent exertion, up to five minutes in a HFHD position results in a small decrease in MVV compared with baseline MVV levels. Even with this decrease, mean MVV levels were still 96% of predicted after five minutes. Though a measurable decrease was found, there was no clinically significant change that would support that this positioning would lead to asphyxia over a five-minute time period.

Brain Emergency Management Initiative for Optimizing Hub-Helicopter Emergency Medical Systems-Spoke Transfer Networks.

OBJECTIVE: Embolectomy is standard for select occlusions up to 24 hours. Transfer patients may have worse outcomes than those originating in embolectomy centers. We developed the Brain Emergency Management Initiative (BEMI) protocol to streamline this transfer process and mimic the urgency that surrounds ST-elevation myocardial infarction cardiac evaluations. METHODS: We conducted an exploratory assessment of consecutive acute telestroke patients transferred for potential intervention in pre-BEMI versus BEMI periods. Times included spoke in, spoke out, hub in, and groin puncture. Outcomes included discharge destination and symptomatic intracranial hemorrhage. RESULTS: Overall, 68 transfers were assessed. There was a higher National Institute of Neurological Disorders and Stroke in BEMI (11 pre-BEMI vs. 20 B.M., P = .01). There were shorter spoke door in to door out (143 vs. 118 minutes, P = .01) and spoke door out to hub door in times (23 minutes pre-BEMI vs. 21 minutes BEMI, P = .001). For embolectomy patients, there was shorter hub door in to reperfusion (83 minutes pre-BEMI vs. 74 minutes BEMI, P = .04) and recombinant tissue plasminogen decision to groin puncture (155 minutes pre-BEMI vs. 130 minutes BEMI; P = .01). There were no symptomatic intracranial hemorrhage or discharge differences. CONCLUSION: In our hub-helicopter emergency medical services-spoke telestroke network, BEMI led to improved evaluation times. BEMI may serve as a model for future rapid stroke transfer pathways.

Physiological effects of a spit sock.

OBJECTIVES: Healthcare providers and law enforcement utilize spit socks to prevent exposure to communicable diseases transmitted by bodily fluid projection from agitated individuals. There are cases in which death is reported due to breathing being limited by a spit sock. There are no formally published studies on their use and safety. The aim of this study was to evaluate whether wearing a spit sock causes a clinically significant impact on breathing. METHODS: Subjects sat with the spit mask over their heads for 15 min and their vital signs and ventilatory parameters were recorded after 5 min, 10 min and 15 min. Data were compared to baseline using Student's t-test with 95% confidence intervals using SPSS. RESULTS: The median age of the 15 subjects was 28 years and 53% were male. There was no significant difference between baseline and wearing the spit sock for 5, 10 or 15 min for heart rate (p = 0.250, p = 0.181, p = 0.546), oxygen saturation (p = 0.334, p = 1.00, p = 0.173), end-tidal pCO2 (p = 0.135, p = 0.384, p = 0.187), and diastolic blood pressure (p = 0.485, p = 0.508, p = 0.915). The respiratory rate was not significantly different after 5 and 10 min (p = 0.898, p = 0.583), but decreased at 15 min (p = 0.048). The systolic blood pressure was lower after 5 and 10 min (p = 0.028, p = 0.045), but not significantly different at 15 min (p = 0.146). No subject indicated distress nor did the study need to be terminated due to pre-determined concerning vital signs or ventilatory parameters. CONCLUSIONS: In healthy subjects there were no clinically significant changes in the physiologic parameters of breathing while wearing a spit sock.

Combination of Polymeric Micelle Formulation of TGFß Receptor Inhibitors and Paclitaxel Produce Consistent Response Across Different Mouse Models of TNBC.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor-beta (TGFß) family of proteins and their receptors (TGFR) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here we evaluated combination treatments using experimental TGFR inhibitors (TGFßi), SB525334 (SB), and LY2109761 (LY) with Paclitaxel (PTX) chemotherapy. These TGFßi target TGFR-I (SB) or both TGFR-I&II (LY). Due to the poor water solubility of these drugs, we incorporated each of them in poly(2-oxazoline) (POx) high-capacity polymeric micelles (SB-POx and LY-POx). We assessed their anti-cancer effect as single agents and in combination with micellar Paclitaxel (PTX-POx) using multiple immunocompetent TNBC mouse models that mimic human subtypes (4T1, T11-Apobec and T11-UV). While either TGFßi or PTX showed a differential effect in each model as single agents, the combinations were consistently effective against all three models. Genetic profiling of the tumors revealed differences in the expression levels of genes associated with TGFß, EMT, TLR-4, and Bcl2 signaling, alluding to the susceptibility to specific gene signatures to the treatment. Taken together, our study suggests that TGFßi and PTX combination therapy using high-capacity POx micelle delivery provides a robust anti-tumor response in multiple TNBC subtype mouse models.

Evaluation of the ventilatory effects of a restraint chair on human subjects.

BACKGROUND: Combative individuals often require physical restraint in the prehospital and law enforcement setting. Specialized restraint chairs have been utilized for this purpose in the latter case, but concern has arisen that restrained individuals are at risk for ventilatory compromise and asphyxiation. OBJECTIVE: We sought to determine if placement in a restraint chair results in alterations of respiratory or ventilatory function. METHODS: We conducted a randomized, cross-over, controlled experimental trial in 10 healthy human volunteers performed at a university exercise physiology laboratory. After exercise on a cycle ergometer to 85% of the age-predicted maximal heart rate, subjects were randomized to either a sitting position or restraint chair with arms, legs, and chest secured using standard law enforcement protocol. Subjects remained in each position for 30 min, during which pulmonary function testing of maximal voluntary ventilation (MVV) was performed at 11 and 30 min. Arterial oxygen saturation (O(2)sat) and end-tidal PCO(2) levels (PETCO(2)) were monitored continuously. Subjects repeated the experimental trial in the alternate position after a 45-min rest period. Measures between restraint and sitting positions were compared using a paired t-test at each time measurement. RESULTS: There was no evidence of hypoxemia. Mean PETCO(2) levels were not statistically different between the two groups at any time (p > 0.05), and there was no evidence of hypercapnia. CONCLUSION: In healthy subjects, placement in a restraint chair resulted in a small decrease in MVV, but did not result in any changes in O(2)sat or PETCO(2).

Preparation of an Orthotopic, Syngeneic Model of Lung Adenocarcinoma and the Testing of the Antitumor Efficacy of Poly(2-oxazoline) Formulation of Chemo-and Immunotherapeutic Agents.

Tumor xenograft models developed by transplanting human tissues or cells into immune-deficient mice are widely used to study human cancer response to drug candidates. However, immune-deficient mice are unfit for investigating the effect of immunotherapeutic agents on the host immune response to cancer (Morgan, 2012). Here, we describe the preparation of an orthotopic, syngeneic model of lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), to study the antitumor effect of chemo and immunotherapeutic agents in an immune-competent animal. The tumor model is developed by implanting 344SQ LUAD cells derived from the metastases of KrasG12D; p53R172HΔG genetically engineered mouse model into the left lung of a syngeneic host (Sv/129). The 344SQ LUAD model offers several advantages over other models: 1) The immune-competent host allows for the assessment of the biologic effects of immune-modulating agents; 2) The pathophysiological features of the human disease are preserved due to the orthotopic approach; 3) Predisposition of the tumor to metastasize facilitates the study of therapeutic effects on primary tumor as well as the metastases ( Chen et al., 2014 ). Furthermore, we also describe a treatment strategy based on Poly(2-oxazoline) micelles that has been shown to be effective in this difficult-to-treat tumor model ( Vinod et al., 2020b ).

Preparation and Characterization of Poly(2-oxazoline) Micelles for the Solubilization and Delivery of Water Insoluble Drugs.

Many new drug development candidates are highly lipophilic compounds with low water solubility. This constitutes a formidable challenge for the use of such compounds for cancer therapy, where high doses and intravenous injections are needed ( Di et al., 2012 ). Here, we present a poly(2-oxazoline) polymer (POx)-based nanoformulation strategy to solubilize and deliver hydrophobic drugs. POx micelles are prepared by a simple thin-film hydration method. In this method, the drug and polymer are dissolved in a common solvent and allowed to mix, following which the solvent is evaporated using mild heating conditions to form a thin film. The micelles form spontaneously upon hydration with saline. POx nanoformulation of hydrophobic drugs is unique in that it has a high drug loading capacity, which is superior to micelles of conventional surfactants. Moreover, multiple active pharmaceutical ingredients (APIs) can be included within the same POx micelle, thereby enabling the codelivery of binary as well as ternary drug combinations ( Han et al., 2012 ; He et al., 2016 ).

Structured case reviews for organizational learning about diagnostic vulnerabilities: initial experiences from two medical centers.

Background An organization's ability to identify and learn from opportunities for improvement (OFI) is key to increasing diagnostic safety. Many lack effective processes required to capitalize on these learning opportunities. We describe two parallel attempts at creating such a process and identifying generalizable lessons and learn from them. Methods Triggered case review programs were created independently at two organizations, Site 1 (Regions Hospital, HealthPartners, Saint Paul, MN, USA) and site 2 (University of California, San Diego). Both used a five-step process to create the review system and provide feedback: (1) identify trigger criteria; (2) establish a review panel; (3) develop a system to conduct reviews; (4) perform reviews; and (5) provide feedback. Results Site 1 identified 112 OFI in 184 case reviews (61%), with 66 (59%) provider OFI and 46 (41%) system OFI. Site 2 focused mainly on systems OFI identifying 105 OFI in 346 cases (30%). Opportunities at both sites were variable; common themes included test result management and communication across teams in peri-procedural care and with consultants. Of provider-initiated reviews, 67% of cases had an OFI at site 1 and 87% at site 2. Conclusions Lessons learned include the following: (1) peer review of cases provides opportunities to learn and calibrate diagnostic and management decisions at an organizational level; (2) sharing cases in review groups supports a culture of open discussion of OFIs; (3) reviews focused on diagnostic safety identify opportunities that may complement other organization-wide review opportunities.

Further study on the physiological effects of an alternative spit mask.

OBJECTIVES: Spit masks are used by law enforcement officers and healthcare providers to protect themselves from the spread of communicable disease by subjects who pose a potential risk of biological exposure by spitting. Little research is available regarding the safety of these masks. However, concerns surround the ability of subjects to properly ventilate while wearing these masks as there are several anecdotal incidents of asphyxiation. A recent pilot study performed by our group showed no significant changes in ventilatory or circulatory parameters in healthy adults wearing a standard spit mask. In this study we aim to further this baseline research by testing physiological parameters in subjects wearing an alternative design of spit mask. METHODS: This prospective study evaluated the changes in respiratory and circulatory parameters in healthy adult subjects wearing a Safariland Tranzport Hood spit mask (SKU: 8320-0-2C) at rest. Baseline measurements of pulse, blood pressure, respiratory rate, oxygen saturation, and end-tidal CO2 were taken while sitting at rest. The spit mask was then placed over the subject's head and repeat measurements were taken at 5, 10, and 15 min. Measurements at 5, 10, and 15 min were compared to baseline using paired t tests with 95% confidence intervals using SPSS. RESULTS: A total of 15 subjects participated in the study. There was no significant difference between baseline and at 5, 10, and 15 min after spit mask application in heart rate (p = 0.246, p = 0.785, p = 0.502, respectively), oxygen saturation (p = 0.751, p = 0.334, p = 1.00, respectively), respiratory rate (p = 0.866, p = 0.270, p = 0.106, respectively), systolic blood pressure (p = 0.385, p = 0.481, p = 0.182, respectively), and diastolic blood pressure (p = 0.832, p = 0.516, p = 0.597, respectively). For end-tidal CO2, there was no significant difference between baseline and at 10 and 15 min (p = 0.586, p = 0.416, respectively). End-tidal CO2 was significantly increased from baseline at 5 min (p = 0.042). CONCLUSIONS: In healthy adult subjects, there were no clinically significant differences in respiratory or circulatory parameters while wearing the Safariland Tranzport Hood spit mask.

Assessment of stress markers in restrained individuals following physical stress with and without sham CED activation.

INTRODUCTION: Law enforcement and pre-hospital care personnel often confront individuals who must be physically restrained. Many are under the influence of illicit substances, and law enforcement officers may need to use a controlled electrical device (CED) to gain control of the individual and they are often placed into the prone maximum restraint (PMR) position. These techniques have previously been evaluated for their physiologic effects. The purpose of this study was to investigate the psychological effects of anticipating and experiencing a sham CED activation in healthy human subjects who were exercised and restrained compared with no sham activation by assessing the differences in a panel of several known biomarkers of stress. METHODS: We performed a randomized, crossover controlled human subject trial to study the stress associated with exercise, physical exhaustion, and restraint with and without an added psychological stress simulating the field use of a CED. Twenty five total subjects; each subject performed two different trials each consisting of a brief period of intense exercise on a treadmill to exhaustion followed by placement in the PMR with and without induced psychological stress. Blood samples were collected for analysis pre and post exercise, as well as 10 min after completion of the exercise. A panel of hormones and stress markers were measured. RESULTS: We found no significant differences in any of the stress biomarkers measured between the two study groups. A trend towards higher levels of copeptin was measured in the sham CED activation arm. CONCLUSION: During a brief period of intense exercise followed by the psychological stress of anticipated CED application, there did not appear to be statistically significant changes in the stress panel of biomarkers measured, only a trend towards significance for higher copeptin levels in the patients exposed to the psychological stress.

High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma.

About 40% of patients with non-small cell lung cancer (NSCLC) have stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause of chemotherapy failure. New immunotherapeutic modalities such as anti-PD-1 immune checkpoint blockade have shown promise; however, response to such strategies is highly variable across patients. Here, we show that our unique poly(2-oxazoline)-based nanomicellar formulation (PM) of Resiquimod, an imidazoquinoline Toll-like receptor (TLR) 7/8 agonist, had a superior tumor inhibitory effect in a metastatic model of lung adenocarcinoma, relative to anti-PD-1 therapy or platinum-based chemotherapy. Investigation of the in vivo immune status following Resiquimod PM treatment showed that Resiquimod-based stimulation of antigen-presenting cells in the tumor microenvironment resulted in the mobilization of an antitumor CD8+ immune response. Our study demonstrates the promise of poly(2-oxazoline)-formulated Resiquimod for treating metastatic NSCLC.

Tactical and subject considerations of in-custody deaths proximal to use of conductive energy devices.

Conductive Energy Devices (CEDs) are used by many law enforcement agencies as a safer way to gain control of subjects, particularly those who are armed, physically resistive, or under the influence of illicit stimulant drugs. This study is an extensive voluntary survey of all police agencies that had a reported CED-related death. The list of deaths was obtained by cross referencing the published lists from Amnesty International and the Arizona Republic occurring between September 1999 and May 31, 2005. One hundred eighteen unique proximity deaths in subjects who had CED activations were identified. These cases involved 96 law enforcement jurisdictions in 26 different states. Each agency was surveyed, with 60 (63%) agencies responding, resulting in data from 65% (77 of 118) of the CED proximity deaths. The majority of deaths were among men (96%), white (46%), and individuals 31 to 40 years of age (38%). Among the 77 subjects, 20 (26%) were armed at some point during the incident including 4 (20%) with a firearm, 8 (40%) with a knife/cutting weapon, and 5 (25%) with a club/baton/blunt force weapon. Undesirable behaviors were also common with 58 (75%) exhibiting noncompliance, 53 (69%) with severe aggression, and 39 (51%) with mild aggression.

EXCITATION study: Unexplained in-custody deaths: Evaluating biomarkers of stress and agitation.

BACKGROUND: Law enforcement personnel often confront violent and dangerous individuals suffering from Excited Delirium Syndrome (ExDS) who need emergent medical evaluation and treatment to optimize the best outcomes for this potentially lethal medical emergency. These subjects typically require physical restraint and use of force measures to control them. We sought to determine if stress-related biomarkers can differentiate ExDS subjects when compared with agitation and stress under other circumstances, including agitation and extreme physical exhaustion and restraint coupled with emotional stressors. METHODS: This was a prospective multi-center study enrolling a convenience sample of patients who presented with agitation or ExDS. Patients were enrolled from three academic emergency departments (ED), two in the United States and one in Canada. Three study groups (SG) included: SG1) patients brought to the ED with ExDS based on the use of standardized clinical criteria; SG2) ED patients with acute agitation who were not in a clinical state of ExDS but required sedation; SG3) a laboratory control group of subjects exercised to physical exhaustion, restrained, and psychologically stressed with threat of Conducted Energy Device (CED) activation. We examined a panel of stress-related biomarkers, including norepinephrine (NE), cortisol, copeptin, orexin A, and dynorphin (Dyn) from the blood of enrolled subjects. RESULTS: A total of 82 subjects were enrolled: 31 in the agitation group, 21 in the ExDS group, and 30 in the laboratory control group. Data were analyzed, comparing the findings between ExDS and the two other groups to determine if specific stress-related biomarkers are associated with ExDS. Biomarker comparisons between subjects identified with ExDS, agitation, and control groups demonstrated that cortisol levels were more elevated in the ExDS group compared with the other groups. Orexin was only significant in ExDs (with Agitated tendency but lot of variability in the group). NE and Dyn increased as response to stress in Agitated and ExDS. CONCLUSIONS: Cortisol levels were more elevated in subjects in the ExDS group compared with the other comparison groups and orexin was elevated in ExDS compared to controls, a trend that did not reach statistical significance in the agitated group. The clinical or diagnostic significance of these difference have yet to be defined and warrants further study.

Twelve-lead electrocardiogram monitoring of subjects before and after voluntary exposure to the Taser X26.

OBJECTIVES: The Taser (Taser International, Scottsdale, Ariz) uses high-voltage electricity to incapacitate subjects. We sought to evaluate cardiac rhythm changes during deployment of the Taser on healthy volunteers. METHODS: This prospective study was performed on 32 healthy volunteer subjects receiving a Taser X26 discharge. The subjects had baseline 12-lead electrocardiogram (ECG) monitoring performed immediately before and within 1 minute after the Taser discharge. Changes in cardiac rhythm, morphology, and interval duration were evaluated. Descriptive statistics and paired-sample t test comparisons are reported. RESULTS: All 32 subjects had an interpretable 12-lead ECG obtained before and after the Taser activation, although 1 subject's post-PR interval could not be determined. The mean age and body mass index were 33 years and 26.5 kg/m2, respectively. Overall, there was a significant increase in heart rate (2.4; 95% confidence interval [CI], 0.0-4.9) and a decrease in PR interval (-6.5; 95% CI, -9.7 to -3.3). When stratified by sex, only the PR interval in men significantly decreased (-5.9; 95% CI, -9.2 to -2.5). There were significant changes in heart rate (4.0; 95% CI, 1.3-6.7), PR interval (-6.0; 95% CI, -11.3 to -0.7), and QT interval (-18.8; 95% CI, -33.2 to -4.3) among those with a normal body mass index, and in PR interval among those who were overweight/obese (-6.7; 95% CI, -10.8 to -2.5). None of the statistically significant differences between ECG measures were clinically relevant. CONCLUSIONS: There were no cardiac dysrhythmia and interval or morphology changes in subjects who received a Taser discharge based on a 12-lead ECG performed immediately before and within 1 minute after a Taser activation.

Thoracic spine compression fracture after TASER activation.

The TASER is a less lethal weapon seeing increased use by police jurisdictions across the country. As a result, subjects of TASER use are being seen with increasing frequency in emergency departments across the country. The potential injury patterns of the device are important for emergency physicians to understand. This report describes the case of an officer who complained of back pain after a single 5-s TASER discharge during a routine training exercise. Subsequent evaluation led to the diagnosis of an acute thoracic vertebral compression fracture. We discuss the potential mechanisms of injury in this case. Because we were unable to find any cases like this in our review of TASER-related injuries, we liken it to compression fractures that have been documented after seizures. We recommend that physicians consider obtaining back radiographs to rule out a vertebral compression fracture in any individual who has sustained a TASER discharge and has ongoing or persistent back pain.

Serum troponin I measurement of subjects exposed to the Taser X-26.

The Taser is a high-voltage, low-amperage conducted energy device used by many law enforcement agencies as a less lethal force weapon. The objective of this study was to evaluate for a rise in serum troponin I level after deployment of the Taser on law enforcement training volunteers. A prospective, observational cohort study was performed evaluating serum troponin I levels in human subjects 6 h after an exposure to the Taser X-26. Outcome measures included abnormal elevation in serum troponin I level (> 0.2 ng/mL). There were 66 subjects evaluated. The mean shock duration was 4.36 s (range 1.2-5 s). None of the subjects had a positive troponin I level 6 h after exposure. It was concluded that human volunteers exposed to a single shock from the Taser did not develop an abnormal serum troponin I level 6 h after shock, suggesting that there was no myocardial necrosis or infarction.