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OBJECTIVES/SPECIFIC AIMS: This study aims to test the hypothesis that bacterial biotransformation of chemotherapeutics promotes gut microbial diversity by enhancing persistence of drug-sensitive taxa. METHODS/STUDY POPULATION: The impacts of doxorubicin on a model community of gut bacteria was investigated in vitro in anaerobic batch culture. The synthetic community was composed of specific members predicted by genomic analysis to be sensitive to the therapeutic (i.e., Clostridium innocuum, Lactobacillus sp.), resistant via putative biotransformation (i.e., Escherichia coli, Klebsiella pneumoniae), or resistant via putative efflux (i.e., Enterococcus faecalis). Bacterial growth was monitored in monocultures by measuring OD600 and standard plate counts, and in mixed cultures by strain-targeted qPCR. Doxorubicin concentration was detected via absorbance assay. RESULTS/ANTICIPATED RESULTS: Strains with predicted resistance to doxorubicin by drug biotransformation significantly lowered concentrations of the drug in culture media. In contrast, E. faecalis proved resistant without evidence of drug transformation. Predicted sensitive strains were growth-repressed by the doxorubicin, but able to grow in spent media where biotransformation had occurred. However, they remained growth-repressed in spent media from E. faecalis where drug transformation had not been observed. Bacterial growth kinetics in mixed batch culture were dependent on starting bacterial concentrations and timing of drug exposure. DISCUSSION/SIGNIFICANCE OF IMPACT: This work will be extended to model microbial community responses to doxorubicin as a factor of microbial interactions and extent of drug transformation prior its exposure to sensitive strains. The resulting model will have translational implications for mitigating health risks during pediatric cancer treatment.

Background: Airway management is a cornerstone in the prehospital care of critically ill or injured patients. Surgical cricothyrotomy offers a rapid and effective solution when oxygenation and ventilation fail using less-invasive techniques. However, the exact indications, incidence, and success of prehospital surgical cricothyrotomy are unknown, with variable rates reported in the literature. This study aimed to examine prehospital indications and success rates for surgical cricothyrotomy within a large, suburban, ground-based Emergency Medical Services (EMS) system. Methods: This is a retrospective analysis of 31 patients who underwent paramedic performed surgical cricothyrotomy from 2012 through 2022. Key demographic parameters were analyzed, including the incidence of cardiac arrest, call type (trauma versus medical), initial airway management attempts, number of endotracheal intubation (ETI) attempts before surgical airway, and average time to the establishment of a surgical airway in relation to the number of ETI attempts. Surgical cricothyrotomy success was defined as the acquisition of four-phase end-tidal capnography reading. The primary data sources were the EMS electronic medical records, and descriptive statistics were calculated. Results: A total of 31 patients were included in the final analysis. Of those who received a surgical cricothyrotomy, 42% (13/31) occurred in the trauma setting, while 58% (18/31) were medical calls. In all patients who underwent surgical cricothyrotomy, the median (IQR) time to the procedure was 17 minutes (IQR = 11-24). In trauma patients, the median time to surgical cricothyrotomy was 12 minutes (IQR = 9-19) versus 19 minutes (IQR = 14-33) in medical patients. End-tidal carbon dioxide (ETCO2) detection and placement success was confirmed in 94% (29/31) of patients. Endotracheal intubation was attempted in 55% (17/31) before subsequent surgical cricothyrotomy, with 29% (9/31) receiving more than one ETI attempt. The median time to surgical cricothyrotomy when multiple prior intubation attempts occurred was 33 minutes (IQR = 23-36) compared to 14.5 minutes (IQR = 6-19) in patients without a preceding intubation attempt. Conclusion: Prehospital surgical airway can be performed by paramedics with a high degree of success. Identification of the need for surgical cricothyrotomy should be determined as soon as possible to allow for rapid securement of the airway and to ensure adequate oxygenation and ventilation. [ABSTRACT FROM AUTHOR]

Introduction: Hyperkalemia (HK) is common and potentially a life-threatening condition. If untreated, HK can progress to ventricular arrhythmia and cardiac arrest. Early treatment reduces mortality in HK. This study evaluates a novel protocol for identification and empiric management of presumed HK in the prehospital setting.Methods: This was a retrospective, observational chart review of a single, large, suburban Emergency Medical Services (EMS) system. Patients treated for presumed HK, with both a clinical concern for HK and electrocardiogram (ECG) changes consistent with HK, from February 2018 through February 2021 were eligible for inclusion. Patients were excluded if found to be in cardiac arrest on EMS arrival. Empiric treatment of HK included administration of calcium, sodium bicarbonate, and albuterol. Post-treatment, patients were placed on cardiac monitoring and adverse events recorded enroute to receiving hospital. Protocol compliance was assessed by two independent reviewers. Serum potassium (K) level was obtained from hospital medical records.Results: A total of 582 patients were treated for HK, of which 533 patients were excluded due to cardiac arrest prior to EMS arrival. The remaining 48 patients included in the analysis had a mean age of 56 (SD = 20) years and were 60.4% (n = 29) male with 77.1% (n = 37) Caucasian, 10.4% (n = 5) African American, and 12.5% (n = 6) Hispanic. Initial blood draw at the receiving facilities showed K >5.0mEq/L in 22 (45.8%), K of 3.5-5.0mEq/L in 23 (47.9%), and K <3.5mEq/L in three patients (6.3%). Independent review of the EMS ECG found the presence of hyperkalemic-related change in 43 (89.6%) cases, and five (10.4%) patients did not meet criteria for treatment due to lack of either appropriate ECG findings or clinical suspicion. No episodes of unstable tachyarrhythmia or cardiac arrest occurred during EMS treatment or transport.Conclusion: The study evaluated a novel protocol for detecting and managing HK in the prehospital setting. It is feasible for EMS crews to administer this protocol, although a larger study is needed to make the results generalizable. [ABSTRACT FROM AUTHOR]

Background: The utility and efficacy of bolus dose vasopressors in hemodynamically unstable patients is well-established in the fields of general anesthesia and obstetrics. However, in the prehospital setting, minimal evidence for bolus dose vasopressor use exists and is primarily limited to critical care transport use. Hypotensive episodes, whether traumatic, peri-intubation-related, or septic, increase patient mortality. The purpose of this study is to assess the efficacy and adverse events associated with prehospital bolus dose epinephrine use in non-cardiac arrest, hypotensive patients treated by a single, high-volume, ground-based Emergency Medical Services (EMS) agency.Methods: This is a retrospective, observational study of all non-cardiac arrest EMS patients treated for hypotension using bolus dose epinephrine from September 12, 2018 through September 12, 2019. Inclusion criteria for treatment with bolus dose epinephrine required a systolic blood pressure (SBP) measurement <90mmHg. A dose of 20mcg every two minutes, as needed, was allowed per protocol. The primary data source was the EMS electronic medical record.Results: Forty-two patients were treated under the protocol with a median (IQR) initial SBP immediately prior to treatment of 78mmHg (65-86) and a median (IQR) initial mean arterial pressure (MAP) of 58mmHg (50-66). The post-bolus SBP and MAP increased to 93mmHg (75-111) and 69mmHg (59-83), respectively. The two most common patient presentations requiring protocol use were altered mental status (55%) and respiratory failure (31%). Over one-half of the patients treated required both advanced airway management (62%) and multiple bolus doses of vasopressor support (55%). A single episode of transient severe hypertension (SBP>180mmHg) occurred, but there were no episodes of unstable tachyarrhythmia or cardiac arrest while en route or upon arrival to the receiving hospitals.Conclusion: These preliminary data suggest that the administration of bolus dose epinephrine may be effective at rapidly augmenting hypotension in the prehospital setting with a minimal incidence of adverse events. Paramedic use of bolus dose epinephrine successfully increased SBP and MAP without clinically significant side effects. Prospective studies with larger sample sizes are needed to further investigate the effects of prehospital bolus dose epinephrine on patient morbidity and mortality. [ABSTRACT FROM AUTHOR]