A Critically Ill Influenza A-Positive Patient With Spontaneous Pneumomediastinum, Superimposed Bacterial Pneumonia, and Bilateral Pneumothoraces.

Influenza most often causes a febrile viral syndrome inclusive of pulmonary irritation with cough, shortness of breath, and congestion. However, severe infection can also occur, causing significant viral pneumonia with Type 1 respiratory failure. and rare but life-altering complications such as pneumomediastinum, secondary bacterial pneumonia, acute respiratory distress syndrome (ARDS), viremia, and death. This was a case of a 20-year-old male with no significant past medical history who presented to the emergency department with shortness of breath and chest discomfort and was found to have Influenza A with Type I respiratory failure requiring High Flow Nasal Cannula (HFNC) and extensive pneumomediastinum, superimposed bacterial pneumonia, and bilateral pneumothoraces. It is possible that complications secondary to influenza A infections could be under-reported due to the extremely high prevalence of the viral infection in this country. In addition, complicated pneumomediastinum from Influenza infection is sparsely documented in young adult males and children, but its clinical course can be dramatic enough to include life-altering complications. This case should serve as a reminder to all emergency medicine providers that when evaluating unstable Influenza A patients, various tests should be considered on a case-by-case basis to risk-stratify the likelihood of emergent pathology.

Now You See It, Now You Don't: Point-of-Care Ultrasound Identification of Left Ventricular Thrombus-in-Transit.

BACKGROUND: Left-sided intracardiac thrombi are most commonly seen in conditions with decreased cardiac flow, such as myocardial infarction or atrial fibrillation. They can be propagated into the systemic circulation, leading to a cerebrovascular accident. Identification of thrombus-in-transit via point-of-care ultrasound (POCUS) has the potential to change patient management given its association with high patient morbidity and mortality. CASE REPORT: An intubated 60-year-old man was transferred to our emergency department for management of altered mental status and seizure-like activity. The patient was markedly hypotensive on arrival, and cardiac POCUS was performed to identify potential causes of hypotension. A left ventricular thrombus-in-transit was identified. The thrombus was notably absent on a repeat POCUS examination < 10 min later, which led to concern for thrombus propagation. Furthermore, the patient's vasopressor requirements had significantly increased in that time period. Subsequent emergent neuroimaging revealed a large ischemic stroke in the left internal carotid and middle cerebral artery distribution. The patient was, unfortunately, deemed to not be a candidate for either thrombectomy or thrombolysis and ultimately expired in the hospital. Why Should an Emergency Physician Be Aware of This? Serial POCUS examinations identified the propagation of this patient's thrombus-in-transit, leading the physician to change the initial presumptive diagnosis and treatment course, and pursue further imaging and workup for ischemic stroke. Identification of a thrombus-in-transit is a clue to potentially underlying critical pathology and should be followed with serial POCUS examinations to assess for treatment efficacy and thrombus propagation.

DO HIGHER DOSES OF NALOXONE INCREASE THE RISK OF PULMONARY COMPLICATIONS?

BACKGROUND: Although naloxone has proven to be an effective opioid reversal agent, concern that high doses of naloxone can cause pulmonary edema may prevent health care providers from administering it in initial high doses. OBJECTIVE: Our aim was to determine whether increased doses of naloxone are correlated with an increase in pulmonary complications in patients presenting to the emergency department (ED) after an opioid overdose. METHODS: This was a retrospective study of patients treated with naloxone by emergency medical services (EMS) or in the ED at an urban level I trauma center and three associated freestanding EDs. Data were queried from EMS run reports and the medical record and included demographic characteristics, naloxone dosing, administration route, and pulmonary complications. Patients were grouped by naloxone dose received, defined as low (≤ 2 mg), moderate (> 2 mg to ≤ 4 mg), and high (> 4 mg). RESULTS: Of the 639 patients included, 13 (2.0%) were diagnosed with a pulmonary complication. There was no difference in the development of pulmonary complications across groups (p = 0.676). There was no difference in pulmonary complications based on the route of administration (p = 0.342). The administration of higher doses of naloxone was not associated with longer hospital stays (p = 0.0327). CONCLUSIONS: Study results suggest that the reluctance of many health care providers to administer larger doses of naloxone on initial treatment may not be warranted. In this investigation, there were no poor outcomes associated with an increase in naloxone administration. Further investigation in a more diverse population is warranted.

The Affordable Care Act: Long-Term Financial Impact on a Level I Trauma Center.

BACKGROUND: Prior studies of the impact of the Affordable Care Act on reimbursement for inpatient trauma care do not include disproportionate share hospital (DSH) funding. Because trauma centers and other safety-net hospitals are sensitive to any changes in financial support, it is essential to include DSH funding in evaluating overall reimbursement. This study analyzes the long-term financial trends, including DSH, of a level I trauma center in Ohio, a state that expanded Medicaid. METHODS: Charges, reimbursement, sources of insurance coverage, Injury Severity Scores, and DSH funding for the trauma patient population of an Ohio American College of Surgeons level 1 trauma center were studied from 2012 to 2017. Data were collected from Transition Systems, Inc. RESULTS: During 2012-2017, self-pay patient cases decreased from 15.0% to 4.1% and commercial insurance patients decreased from 34.2% to 27.6%. The percentage of Medicaid patients increased from 15.5% to 27.1%; however, Medicaid reimbursement average per case declined from $17,779 in 2012 to $10,115 in 2017 (a decline of 43.1%). Self-pay charges decreased from $22.0 million to $6.7 million. Total DSH funding, compensation given to hospitals that disproportionately treat underserved populations, decreased 17.4%. CONCLUSIONS: Self-pay charges and self-pay patients decreased dramatically; Medicaid patients and charges increased substantially in the years after the implementation of the Affordable Care Act at our trauma center. However, there was a decrease in commercial insurance, which had the highest reimbursement for our hospital, and a significant decline in DSH, a critical supplemental source of funding for safety-net hospitals.

Lack of Constitutively Active DNA Repair Sensitizes Glioblastomas to Akt Inhibition and Induces Synthetic Lethality with Radiation Treatment in a p53-Dependent Manner.

Treatment refractory glioblastoma (GBM) remains a major clinical problem globally, and targeted therapies in GBM have not been promising to date. The Cancer Genome Atlas integrative analysis of GBM reported the striking finding of genetic alterations in the p53 and PI3K pathways in more than 80% of GBMs. Given the role of these pathways in making cell-fate decisions and responding to genotoxic stress, we investigated the reliance of these two pathways in mediating radiation resistance. We selected a panel of GBM cell lines and glioma stem cells (GSC) with wild-type TP53 (p53-wt) and mutant TP53, mutations known to interfere with p53 functionality (p53-mt). Cell lines were treated with a brain permeable inhibitor of P-Akt (ser473), phosphatidylinositol ether lipid analogue (PIA), with and without radiation treatment. Sensitivity to treatment was measured using Annexin-V/PI flow cytometry and Western blot analysis for the markers of apoptotic signaling, alkaline COMET assay. All results were verified in p53 isogenic cell lines. p53-mt cell lines were selectively radiosensitized by PIA. This radiosensitization effect corresponded with an increase in DNA damage and a decrease in DNA-PKcs levels. TP53 silencing in p53-wt cells showed a similar response as the p53-mt cells. In addition, the radiosensitization effects of Akt inhibition were not observed in normal human astrocytes, suggesting that this treatment strategy could have limited off-target effects. We demonstrate that the inhibition of the PI3K/Akt pathway by PIA radiosensitizes p53-mt cells by antagonizing DNA repair. In principle, this strategy could provide a large therapeutic window for the treatment of TP53-mutant tumors. Mol Cancer Ther; 17(2); 336-46. ©2017 AACRSee all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology."