Purpose: Optimal rasburicase dosing remains unknown. This study evaluated outcomes of single rasburicase 4.5 mg doses when treating moderate (12 to <15 mg/dL) versus high (>= 15 mg/dL) uric acid (UA) levels. Methods: This retrospective observational cohort study included patients with an active malignancy and tumor lysis syndrome (TLS) who received rasburicase 4.5 mg. Patients were categorized by UA levels before administration of rasburicase. The primary outcome was UA normalization (<8 mg/dL) 24 hours post rasburicase administration. Secondary outcomes included repeat rasburicase dose(s) within 72 hours and renal replacement therapy (RRT) within 7 days. Nominal and continuous data were analyzed using chi squared or Fisher's exact and Wilcoxon rank-sum or Student's t test, respectively. Multivariate regression analysis explored risk factors for continued hyperuricemia. Results: After screening of 428 patients, 124 moderate and 95 high baseline UA values were included. Overall, baseline characteristics were similar between cohorts. The primary outcome was achieved more often in the moderate cohort (92.7% vs 67.4% [P < 0.001]). More high cohort patients received repeat rasburicase doses (8.1% vs 21.1% [P = 0.009]) with no difference in RRT frequency. Risk factors for continued hyperuricemia included baseline UA, potassium and body mass index. Conclusion: A single dose of rasburicase 4.5 mg was less effective in achieving UA normalization in patients with a baseline UA of >= 15 mg/dL vs 12 to <15 mg/dL, without significant differences in patient-oriented outcomes such as RRT. Higher initial doses of rasburicase may be needed for patients with a baseline UA of >= 15 mg/dL. Additional studies are needed to determine optimal dosing for these patients.

PURPOSE: Adaptive flow (AF) is a patient-comfort feature used in the volume control mode on some mechanical ventilators.When activated, AF allows for increased flow in response to detection of excessive patient demand, which is sensed by the decreased airway pressure in the circuit.Since flow is increased over a fixed inspiratory time, larger tidal volumes (Vts) may be delivered than the desired setting.This study sought to assess the impact of AF on the ability to achieve target Vt < 8 mL/kg.Here we present a preliminary analysis of that data. METHODS:We conducted a retrospective cohort study of medical intensive care unit patients receiving volume-targeted mechanical ventilation for at least 48 hours in the year before (2017)(2018) and the year after (2018-2019) system-wide implementation of a ventilator featuring AF.The primary outcome was the proportion of patients receiving an average Vt > 8 mL/kg of ideal body weight (IBW) during the first 48 hours of intubation.Secondary outcomes included the median exhaled Vt, the median difference between set and exhaled Vt, new incidence of acute respiratory distress syndrome (ARDS), need for refractory hypoxemia interventions, ICU and hospital mortality, ICU and hospital length-of-stay, and ventilator-free days. RESULTS:Of 2680 charts pulled, to date we have screened 1482 and included 235 patients, 131 in the control group and 104 in the AF group.At baseline, patients in the control group were more likely to have asthma, COPD, ARDS on presentation, and had higher sequential organ failure assessment scores.Despite no difference in set tidal volume between groups, patients in the AF group were more likely to receive an average Vt > 8 mL/kg (13.7% vs 6.4%; odds ratio 3.4, 95% confidence interval 1.7 -6.7; p ¼ 0.0003).The median IBW-adjusted Vt was 6.6 mL/kg (interquartile range (IQR) 6.3 -7.2) and 7.2 mL/kg (IQR 6.8 -8.3) for the control and AF groups respectively (p < 0.0001).The median difference between set and delivered Vt was +27.7 mL (or +0.44 mL/kg) in the control group and +59.6 mL (or +0.97 mL/kg) in the AF group (p < 0.0001).These differences remained significant after adjusting for baseline characteristics.Of the secondary outcomes evaluated, new incidence of ARDS, use of neuromuscular blockade, and use of inhaled pulmonary vasodilators were all higher in the control group, but none remained significant after adjustment for covariates on multivariate logistic regression. CONCLUSIONS:This small preliminary analysis of a large retrospective study shows that volume control ventilation featuring AF is associated with delivery of average Vts higher than is recommended for lung protective ventilation.To assess the impact on patient-oriented outcomes will require ongoing data collection and analysis.CLINICAL IMPLICATIONS: AF may improve patient comfort at the expense of using improper lung protective ventilation.A larger sample size will be needed to evaluate whether this translates into increased risk of ventilator-induced lung injury, particularly for patients with ARDS.

INTRODUCTION: Pyogenic liver abscess (PLA) is an uncommon complication of endoscopic retrograde cholangiopancreatography (ERCP) (1).Transdiaphragmatic rupture resulting in empyema has rarely been reported.Here we present a patient who developed acute hypoxemic respiratory failure and septic shock during treatment for PLA with imaging showing complete translocation of the fluid collection into the right pleural space.CASE PRESENTATION: An 89 year-old male with medical history of atrial fibrillation, coronary artery disease, ESRD, and recent choledocholithiasis presented to an outside hospital with fever and abdominal pain.Two months prior, he was diagnosed with choledocholithiasis, requiring serial ERCPs, with sphincterotomy, pancreatic stent placement, and eventual stone extraction.A CT of the abdomen/pelvis was obtained and revealed a 18 x 12 x 13 cm loculated collection with an air-fluid level within the liver, suspicious for a PLA.He was started on empiric piperacillin-tazobactam and transferred to our hospital for further treatment.Several hours after arrival, he acutely decompensated with development of shock and acute hypoxemic respiratory failure, requiring vasopressors, bilevel positive airway pressure, and transfer to the intensive care unit.A chest X-Ray showed near complete opacification of the right hemithorax with leftward shift of cardiomediastinal structures.A 14-french pigtail chest tube was inserted with initial output of 1.5 liters of frank pus.Follow-up CT demonstrated resolution of the large hepatic abscess and new moderate hydropneumothorax, consistent with empyema due to trans-diaphragmatic abscess rupture.The empyema resolved after 6 days of chest tube drainage with a single dose of intrapleural fibrinolytics.Fluid cultures grew Fusobacterium nucleatum.He was treated with IV antibiotics for 6 weeks.In the ensuing months he was lost to follow up at our institution and later noted to be deceased for an unknown reason.DISCUSSION: Spontaneous rupture of PLA occurs in roughly 3.8% of cases.Diameter greater than 6cm, history of cirrhosis, presence of gas in the collection, and other septic metastases are common risk factors for rupture (2).Contained ruptures can typically be managed by percutaneous drainage and antibiotics, as was done in this case, while ruptures resulting in peritonitis typically require urgent surgery (1, 2).The exact mechanism by which a PLA can result in ipsilateral empyema has not been fully elucidated.Rhythmic compressive forces by the diaphragm may weaken the fibrous abscess capsule leading to rupture.As occurs in hepatic hydrothorax, the negative pleural-peritoneal pressure gradient generated during spontaneous respiration then likely favors migration of the fluid into the pleural space across a small diaphragmatic defect (3). CONCLUSIONS:Transpleural rupture of a pyogenic liver abscess is a rare complication that can result in rapid clinical decompensation with a high mortality rate.This case highlights the importance of rapid identification and appropriate management when such an event occurs.

Eisinger, Gregory; Osman, Wissam; Prather, Evan; Julian, Mark; Gavrilin, Mikhail; Crouser, Elliott; Wewers, Mark Author Information

Objective: To assess the impact of the national shortage of injectable opioids during the winter of 2017-2018 on the use of ketamine infusion for analgosedation in the medical intensive care unit (MICU).Design: A retrospective cohort study.Setting: Single-center tertiary care MICU at The Ohio State University Wexner Medical Center.Patients: All patients who received continuous infusion of ketamine to facilitate mechanical ventilation between May 1, 2015 and September 1, 2018.Measurements and main results: Seventy-seven patients were identified during the study time frame: 43 before and 19 during the opioid shortage. During the peak of the shortage, there was a sevenfold increase in orders for ketamine infusion (2.2 patients/week vs 0.32 patients/week; p < 0.001). Median time from the start of mechanical ventilation to initiation of ketamine infusion was significantly shorter during the shortage (14.1 hours) versus before (51.2 hours; p = 0.03). There was a trend toward adding ketamine into the sedation regimen earlier during the shortage (mean number of drips added prior to ketamine was 2.74 during the shortage vs 3.3 before; p = 0.06). There was also a trend toward increased use of ketamine infusion as monotherapy during (21.1 percent of patients) versus before the shortage (7 percent), though this did not reach statistical significance (p = 0.19).Conclusion: The national opioid shortage may have led to earlier and more frequent use of ketamine infusion for anaglosedation in mechanically ventilated MICU patients.

OBJECTIVES:. Increased monocyte distribution width (MDW) has recently been shown to be a reliable indicator of early sepsis detection. This study therefore sought to determine if inflammasome activation can be linked to monocyte size changes in sepsis. DESIGN:. An in vitro sepsis model using bacterial endotoxin (lipopolysaccharide [LPS]) to study the effect of inflammasome activation on monocyte cell size distribution by microscopy and MDW measurements using a standard clinical hematology analyzer. SETTING:. University research laboratory. SUBJECTS:. Healthy adult volunteers and cultured human monocyte cells in wild-type state and after clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 knockout of key inflammasome components (apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin-D). INTERVENTIONS:. In vitro treatment of specimens with bacterial LPS. MEASUREMENTS AND MAIN RESULTS:. Wild-type THP1 cells demonstrated a significant increase in cell area (207 μm2 [159–400 μm2] vs 160 μm2 [134–198 μm2]; p < 0.001) and distribution width (198 vs 55 μm2; p < 0.0001) by microscopy following treatment with LPS. Increased MDW correlated with inflammasome activation as demonstrated by release of interleukin (IL)-1β and with the presence of large distended pyroptotic cells by microscopy. All of these effects were blocked in the inflammasome knockout cells. Whole blood samples treated similarly also demonstrated IL-1β release and increased MDW (median 24.7 U [22.2–27.2 U] vs 16.3 U [15.1–17.6 U]; p = 0.008) as measured using the Beckman-Coulter Unicel DxH900 analyzer. When peripheral blood mononuclear cells were isolated prior to treatment with LPS, microscopy confirmed the presence of large pyroptotic cells correlating to IL-1β release in the human subject samples as well. CONCLUSIONS:. The increased MDW seen in patients with sepsis can be reproduced in an in vitro sepsis model and blocked using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 technology to inactivate the inflammasome. These findings suggest that pyroptotic cellular swelling underlies changes in MDW in septic patients and connect MDW to early events in the inflammatory cascade of sepsis.

Sodhi, Angad; Arnold, Joshua; Doepker, Bruce; Elefritz, Jessica; Eisinger, Gregory; McLaughlin, Eric; Parcel, Kaeli Author Information

"Pulmonary Artery Cannulation Complicating Tube Thoracostomy." Annals of the American Thoracic Society, 19(4), pp. 682–684

Corticosteroids and immunomodulatory therapies are widely used to treat patients with severe coronavirus disease 2019 (COVID-19). Janus kinase (JAK) inhibitors such as tofacitinib have been recently studied as adjuvants in the treatment of COVID-19. Although immunomodulatory therapies may be linked to decreased mortality rates in the acute phase, subsequent severe infectious complications may result from them. We describe a case of a multiorgan system failure secondary to disseminated primary herpes simplex virus 1 (HSV-1) infection and hemophagocytic lymphohistiocytosis (HLH) following treatment with tofacitinib and high-dose dexamethasone therapy for severe COVID-19. Early diagnosis and treatment of these life-threatening conditions may have a significant impact on COVID-19 patients’ outcomes.

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Broncholithiasis refers to calcified material within the airway lumen, often resulting from granulomatous reaction to endemic pathogens such as M. tuberculosis or Histoplasma, or aspiration of foreign material. Histoplasma broncholiths are thought to originate from adjacent lymph nodes that erode into the airway lumen. Here we present a case of a large isolated endobronchial broncholith secondary to Histoplasma without associated lymphadenopathy or parenchymal lung lesions. CASE PRESENTATION: A 69 year-old female with GERD presented with one month of dyspnea, cough, and wheezing thought to occur after a popcorn kernel aspiration. She was treated twice for bronchitis without improvement and was diagnosed with COPD based on obstruction on spirometry. The patient denied smoking or other inhalational exposures. Vital signs and oxygenation were normal on our evaluation. A CT pulmonary angiogram showed a 1.3 cm calcified foreign body (FB) consistent with an aspirated tooth in the left mainstem bronchus without significant lymphadenopathy. Bronchoscopy showed a white-yellow multilobulated FB partially embedded in and nearly occluding the left mainstem bronchus. Removal of the FB revealed a deep but not transmural ulceration of the mucosa. Though it grossly resembled a popcorn kernel, histologic examination of the broncholith showed well-formed granulomas and yeast forms consistent with Histoplasma capsulatum. The patient felt immediate relief of dyspnea post-removal and on follow up denied any symptoms. She was discharged and scheduled for repeat testing to ensure no further evidence of fungal disease. DISCUSSION: Although broncholithiasis from Histoplasma granulomata is common, to our knowledge this is the first report of the disease presenting as a solitary endobronchial broncholith. Given that no adjacent lymphadenopathy and/or calcifications were noted on CT, this case was likely secondary to calcification of a primary endobronchial inoculum. Patients with symptomatic or obstructing broncholithiasis should undergo attempted removal either with bronchoscopy or surgical intervention. Bronchoscopic removal should be undertaken with great caution since the extraluminal origin of many broncholiths can result in airway perforation or major hemorrhage with manipulation. Large broncholiths such as this sometimes require laser lithotripsy to facilitate extraction. CONCLUSIONS: Broncholithiasis is a condition often associated with pulmonary and mediastinal histoplasmosis and can present with transmural bronchial invasion. Isolated endobronchial lesions are uncommon. Prompt imaging and endoscopic evaluation is key to accurate diagnosis. Careful consideration of transmural extension and involvement of extrabronchial structures is crucial. REFERENCE #1: Alshabani K, Ghosh S, Arrossi AV, Mehta AC. Broncholithiasis: A Review. Chest. 2019 Sep;156(3):445-455. REFERENCE #2: Krishnan S, Kniese CM, Mankins M, Heitkamp DE, Sheski FD, Kesler KA. Management of broncholithiasis. J Thorac Dis. 2018;10(Suppl 28):S3419-S3427. REFERENCE #3: Olson EJ, Utz JP, Prakash UB. Therapeutic bronchoscopy in broncholithiasis. Am J Respir Crit Care Med. 1999 Sep;160(3):766-70. DISCLOSURES: No relevant relationships by Gregory Eisinger, source=Web Response No relevant relationships by Molly Howsare, source=Web Response No relevant relationships by Meghana Moodabagil, source=Web Response No relevant relationships by Alberto Revelo, source=Web Response No relevant relationships by Konstantin Shilo, source=Web Response

TOPIC: Procedures TYPE: Medical Student/Resident Case Reports INTRODUCTION: To our knowledge, no published case reports of tracheal ring aspiration following surgical tracheostomy exist in the literature. In the surgical approach, a Bjork flap technique is often utilized in which the inferior portion of the anterior trachea is sutured to the skin to secure the tracheostomy lumen. Based on this patient's course, we suspect that the surgical approach resulted in separation of a tracheal ring, which was then aspirated. CASE PRESENTATION: A 58-year-old male with history of quadriplegia who required a Bjork flap surgical tracheostomy a month prior due to recurrent respiratory failure. Post tracheostomy, his course was complicated by recurrent mucous plugging and he presented to the medical ICU from long term acute care facility with worsening hypoxemia and elevated airway pressures. During urgently performed bronchoscopy, extensive mucous plugging was evacuated from the left mainstem bronchus along with a small foreign body that was removed from the medial segment of the left lower lobe bronchus (Figure 1).Immediately following the procedure, the patient's oxygen saturation and airway pressures improved, and his ventilator settings were able to be weaned down significantly. No further episodes of mucous plugging requiring bronchoscopy were subsequently noted. Unfortunately, over the next several weeks he went on to develop further complications of a decubitus ulcer including septic shock and renal failure. His family ultimately made the decision transition to comfort care measures and the patient died. Histologic examination of the left lower lobe endobronchial foreign body revealed a fragment of a large airway wall morphologically consistent with a tracheal ring fragment (Figure 2). In light of the prior tracheostomy procedure, the most likely diagnosis was aspiration of a fragment of tracheal ring during the construction of a Bjork flap, which served as a nidus for mucus hypersecretion and recurrent airway obstruction. DISCUSSION: Although our patient's complication appears to be rare, it is important to be aware of, both for clinicians who perform surgical tracheostomy and those who care for these patients afterward. There are many factors that contribute to recurrent mucous plugging following tracheostomy. However, attention should be given on airway inspection to the possible presence of foreign bodies that could serve as a nidus for airway obstruction, infection, and mucus secretion. CONCLUSIONS: Tracheal ring aspiration is a possible complication of surgical tracheostomy using the Bjork flap technique. REFERENCE #1: Dukes HM. Tracheostomy. Thorax. 1970;25(5):573-576 REFERENCE #2: Hammarfjord O, Ekanayake K, Norton J, Stassen LFA. Limited dissection and early primary closure of the tracheostomy stoma in head and neck oncology operations: A retrospective study of 158 cases. Int J Oral Maxillofac Surg. 2015;44(3):297-300 REFERENCE #3: Sagiv D, Nachalon Y, Mansour J, et al. Awake tracheostomy: Indications, complications and outcome. World J Surg. 2018;42(9):2792-2799 DISCLOSURES: No relevant relationships by Matthew Barraza, source=Web Response No relevant relationships by Gregory Eisinger, source=Web Response No relevant relationships by Lynn Fussner, source=Web Response No relevant relationships by Konstantin Shilo, source=Web Response

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: Gasdermin-D (GSDMD) is a pore-forming molecule that serves as the final effector of pyroptosis (a form of inflammatory cell death) following activation of the cellular inflammasome in monocytes. Disulfiram (DSM), a drug used in the treatment of alcohol abuse, has recently been shown to inhibit GSDMD via disruption of pore formation after its cleavage by the inflammatory caspases (1, 4, and 5). The aim of this study was to elucidate the inhibitory effects of DSM on GSDMD-mediated pyroptosis and explore its role as a potential therapeutic agent in sepsis. METHODS: A series of experiments was conducted using THP1 cells (a human monocytic cell line) or purified human monocytes from the blood of healthy donors. Samples were pretreated with DSM in various concentrations 30 minutes prior to inflammasome activation with bacterial lipopolysaccharide (LPS). Cells were then assessed under light microscopy for swelling and fluorescent microscopy for the formation of ASC specks (activated oligomers of the adaptor protein required for caspase activation). Cell death was assessed using a lactate dehydrogenase (LDH) cytotoxicity assay. Interleukin-1-beta (IL1ß) release was measured by ELISA. GSDMD cleavage, pro-IL1ß synthesis, and caspase-1 cleavage were assessed using immunoblots. RESULTS: Unexpectedly, low dose DSM accentuated inflammasome activation. Dramatic inflammasome induction was observed at a concentration of 10uM, a dose associated with near peak inhibition in the prior study. However, higher doses of 50 to 100 uM suppressed pyroptosis as evidenced by loss of cell swelling and ASC speck formation, as well as LDH and IL-1ß release. The DSM effect occurred downstream of caspase-1 activation as evidenced by preserved intracellular pro-IL1ß synthesis and caspase-1 cleavage in the presence of DSM. Contrary to the prior report, GSDMD cleavage appeared to be inhibited at these higher doses. CONCLUSIONS: DSM unexpectedly exhibits upstream activation of the inflammasome at low doses but downstream inhibition at high doses. CLINICAL IMPLICATIONS: Although DSM's inhibitory effects on inflammasome function make it a promising agent for the future treatment of acute inflammatory conditions such as sepsis and covid-19, our results indicate that further study is needed to better characterize its possible activating effects at lower concentrations. DISCLOSURES: Collaboration via BARDA grant funding relationship with Beckman Coulter, Inc. Please note: 9/19/2019-8/31/2014 Added 04/27/2021 by Elliott Crouser, source=Web Response, value=Grant/Research Support No relevant relationships by Gregory Eisinger, source=Web Response No relevant relationships by Mikhail Gavrilin, source=Web Response No relevant relationships by Wissam Osman, source=Web Response No relevant relationships by Evan Prather, source=Web Response No relevant relationships by Mark Wewers, source=Web Response

Background: The ideal diagnostic test for suspicion of CAD in the emergency department (ED) is unknown. We developed the Buckeye Optimality Stress Score (BOSS) to assess ischemic evaluation (IE) appropriateness and impact on ED readmission. Methods: The BOSS score assigns points for each type of IE based upon published guidelines. We retrospectively calculated the BOSS score on all ED patients with IE orders (8/2017-11/2017). IE orders were assigned a category of optimal vs. suboptimal reflecting whether or not the IE with the highest BOSS score was used ( optimal ) or not ( suboptimal ). Results: In total, 251 patients were referred from the ED for IE (54 ± 12 years old, women 132 (53%)) of which 182 (73%) had a suboptimal BOSS score. The modality most likely to be optimal was CTA, accounting for 29 (44%) of all IE orders. Patients with diabetes, HTN and CAD were more likely to have a suboptimal BOSS. Cardiology was consulted in 75 (30%), and this was associated with higher CTA IE orders (26 (36%) vs. 26 (15%), p<0.001). Re-presentation to the ED was more likely in those with a suboptimal BOSS on initial IE order (11 (6.1%) vs. 0 (0%), p<0.04). Conclusion: The majority of IE orders from the ED received a suboptimal BOSS, perhaps indicating a gap in understanding of current IE guidelines. These patients were more likely to return to the ED for continued symptoms. Further prospective study of the utility of BOSS score in predicting recurrent presentation and subsequent testing is warranted.

A 59-year-old man came to the ED with out-of-hospital cardiac arrest (CA) after a witnessed convulsive spell. On the scene, he complained of chest pressure and dizziness. En route, he had developed pulseless electrical activity (PEA) and received advanced cardiac life support for 5 min before initial return of spontaneous circulation (ROSC). On arrival, the patient appeared moribund. He had weak central pulses and no evidence of trauma. Initial blood gas was notable for a pH of 6.8 and lactate at 16.6 mmol/L. The patient’s ECG is shown in Figure 1. Bedside point-of-care ultrasound (POCUS) was done within 5 min of arrival (Video 1). Question: On the basis of the sonographic findings, what is the leading differential diagnosis for this patient and the next step if he subsequently arrests? Answer: A transthoracic subxiphoid view of the heart demonstrated a moderate circumferential pericardial effusion with right ventricular collapse, indicative of tamponade physiology Shortly after arrival, the patient again lost pulses. Bedside pericardiocentesis was performed with 15 cm3 of bloody return resulting in ROSC and sonographic resolution of the tamponade physiology (Fig 2). Concern was raised for aortic dissection as the etiology of the hemopericardium. Transesophageal echocardiography (TEE) was performed at the bedside and confirmed acute type A aortic dissection (AADA), extending into the coronary arteries (Video 2). The patient experienced two additional PEA arrests with ROSC subsequent to standard advanced cardiac life support. Massive transfusion and vasopressors were initiated with a goal of permissive hypotension. On the basis of the TEE findings, the patient was taken directly to the cardiac surgery suite for AADA repair. Rapid POCUS is a valuable tool for identifying potentially reversible etiologies of cardiac arrest such as pericardial effusion or right heart strain, especially in PEA.1Long B. Alerhand S. Maliel K. Koyfman A. Echocardiography in cardiac arrest: an emergency medicine review.Am J Emerg Med. 2018; 36: 488-493Abstract Full Text Full Text PDF Scopus (30) Google Scholar, 2Labovitz A.J. Noble V.E. Bierig M. et al.Focused cardiac ultrasound in the emergent setting: a consensus statement of the American Society of Echocardiography and American College of Emergency Physicians.J Am Soc Echocardiogr. 2010; 23: 1225-1230Abstract Full Text Full Text PDF PubMed Scopus (502) Google Scholar, 3Tsou P.Y. Kurbedin J. Chen Y.S. et al.Accuracy of point-of-care focused echocardiography in predicting outcome of resuscitation in cardiac arrest patients: a systematic review and meta-analysis.Resuscitation. 2017; 114: 92-99Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar When performed by trained providers, POCUS may guide life-saving interventions. A prospective study found that POCUS led to treatment changes for 78% patients with shock or CA, including interventions such as pericardiocentesis.4Breitkreutz R. Price S. Steiger H.V. et al.Emergency Ultrasound Working Group of the Johann Wolfgang Goethe-University Hospital, Frankfurt am Main. Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: a prospective trial.Resuscitation. 2010; 81: 1527-1533Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar Dissection flaps may even be visualized in the transabdominal short and long-axis views (Videos 3, 4, Narration Video). AADA is rare and challenging to diagnose because of its variability in presentation.5Hagan P. Nienaber C. Isselbacher E. et al.The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease.JAMA. 2000; 283: 897-903Crossref PubMed Scopus (2673) Google Scholar The average time from arrival to diagnosis has been reported as high as 200 min.6Cruz I. Stuart B. Caldeira D. et al.Controlled pericardiocentesis in patients with cardiac tamponade complicating aortic dissection: experience of a centre without cardiothoracic surgery.Eur Heart J Acute Cardiovasc Care. 2014; 4: 124-128Crossref Scopus (16) Google Scholar Cardiac tamponade may be present in 18.7% of cases7Gilon D. Mehta R.H. Oh J.K. et al.Characteristics and in-hospital outcomes of patients with cardiac tamponade complicating type A acute aortic dissection.Am J Cardiol. 2009; 103: 1029-1031Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar and is associated with more than 90% mortality without early surgical intervention.7Gilon D. Mehta R.H. Oh J.K. et al.Characteristics and in-hospital outcomes of patients with cardiac tamponade complicating type A acute aortic dissection.Am J Cardiol. 2009; 103: 1029-1031Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Because of poor pericardial compliance, acute accumulation of even minimal fluid can cause tamponade physiology. Even with repair, in-hospital mortality is doubled when tamponade is present (44% vs 20.5%).7Gilon D. Mehta R.H. Oh J.K. et al.Characteristics and in-hospital outcomes of patients with cardiac tamponade complicating type A acute aortic dissection.Am J Cardiol. 2009; 103: 1029-1031Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Pericardiocentesis has classically been discouraged in AADA because of concern for clot disruption causing worsening hemorrhage. Multiple case series support controlled pericardiocentesis for temporary stabilization while awaiting definitive surgical treatment in unstable patients.6Cruz I. Stuart B. Caldeira D. et al.Controlled pericardiocentesis in patients with cardiac tamponade complicating aortic dissection: experience of a centre without cardiothoracic surgery.Eur Heart J Acute Cardiovasc Care. 2014; 4: 124-128Crossref Scopus (16) Google Scholar,8Hayashi T. Tsukube T. Yamashita T. et al.Impact of controlled pericardial drainage on critical cardiac tamponade with acute type A aortic dissection.Circulation. 2012; 126: S97-S101Crossref PubMed Scopus (39) Google Scholar Aspiration should be limited to the minimum volume required to restore hemodynamics, typically 40 cm3 or less.6Cruz I. Stuart B. Caldeira D. et al.Controlled pericardiocentesis in patients with cardiac tamponade complicating aortic dissection: experience of a centre without cardiothoracic surgery.Eur Heart J Acute Cardiovasc Care. 2014; 4: 124-128Crossref Scopus (16) Google Scholar,8Hayashi T. Tsukube T. Yamashita T. et al.Impact of controlled pericardial drainage on critical cardiac tamponade with acute type A aortic dissection.Circulation. 2012; 126: S97-S101Crossref PubMed Scopus (39) Google Scholar For facilities without the means to perform cardiothoracic surgery or when prolonged delays are anticipated, insertion of a pericardial drain may be favorable. The differential diagnosis of acute hemopericardium is limited (Table 1). Many of the possible etiologies require immediate intervention for survival.Table 1Differential Diagnosis of Acute Hemopericardium•Free wall rupture (myocardial infarction, left ventricular aneurysm)•Ascending aortic dissection•Pericarditis•Trauma (iatrogenic, blunt/penetrating)•Malignancy•Coronary artery aneurysm Open table in a new tab While prompt POCUS in CA is essential, TEE offers many advantages including assessment of the quality of chest compressions,9Blaivas M. Transesophageal echocardiography during cardiopulmonary arrest in the emergency department.Resuscitation. 2008; 78: 135-140Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 10Fair J. Mallin M. Mallemat H. et al.Transesophageal echocardiography: guidelines for point-of-care applications in cardiac arrest resuscitation.Ann Emergency Med. 2018; 71: 201-207Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 11Teran F. Dean A.J. Centeno C. et al.Evaluation of out-of-hospital cardiac arrest using transesophageal echocardiography in the emergency department.Resuscitation. 2019; 137: 140-147Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar shorter pauses during CPR,12Fair III, J. Mallin M.P. Adler A. et al.Transesophageal echocardiography during cardiopulmonary resuscitation is associated with shorter compression pauses compared with transthoracic echocardiography.Ann Emerg Med. 2019; 73: 610-616Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar and early identification of pathology such as AADA in patients too unstable to undergo CT scanning. Although traditionally performed by a cardiologist, use of TEE by trained emergency physicians is increasing and may expedite patient care in undifferentiated CA. One small study of 33 TEEs in CA showed a diagnostic, therapeutic, or prognostic impact in 97% of patients.11Teran F. Dean A.J. Centeno C. et al.Evaluation of out-of-hospital cardiac arrest using transesophageal echocardiography in the emergency department.Resuscitation. 2019; 137: 140-147Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Another study of 54 ED TEEs found treatment changes affecting CPR, prognostication, volume status, pressor/inotrope titration, and procedural guidance in 78% of patients.13Arntfield R. Pace J. Hewak M. Thompson D. Focused transesophageal echocardiography by emergency physicians is feasible and clinically influential: observational results from a novel ultrasound program.J Emerg Med. 2016; 50: 286-294Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Competency standards by the American College of Emergency Physicians for TEE in the ED and protocols for implementation have been previously published.10Fair J. Mallin M. Mallemat H. et al.Transesophageal echocardiography: guidelines for point-of-care applications in cardiac arrest resuscitation.Ann Emergency Med. 2018; 71: 201-207Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar,14American College of Emergency Physicians Board of DirectorsGuidelines for the use of transesophageal echocardiography (TEE) in the ED for cardiac arrest.Ann Emerg Med. 2017; 70: 442-445Abstract Full Text Full Text PDF Scopus (25) Google Scholar Emergency medicine residents have used TEE in simulated arrest scenarios with a high degree of precision and accuracy.15Byars D. Tozer J. Joyce J. et al.Emergency physician-performed transesophageal echocardiography in simulated cardiac arrest.West J Emerg Med. 2017; 18: 830-834Crossref PubMed Scopus (11) Google Scholar Simplified three-view protocols succinctly direct emergency physicians.10Fair J. Mallin M. Mallemat H. et al.Transesophageal echocardiography: guidelines for point-of-care applications in cardiac arrest resuscitation.Ann Emergency Med. 2018; 71: 201-207Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar After undergoing successful aortic reconstruction, the patient was extubated the next day. Remarkably, he was discharged neurologically intact within 2 weeks, and he returned to independent living and work within 2 months. This patient highlights the benefit of early POCUS in CA, the usefulness of pericardiocentesis to achieve ROSC in tamponade, and the advantages of urgent TEE in the ED. Early multidisciplinary collaboration with cardiology and cardiothoracic surgery is essential for effective treatment of suspected AADA. This patient was in the ED for less than 70 min, a benchmark that never would have been possible without the use of ED POCUS and TEE. 1.Early point-of-care ultrasound in patients with undifferentiated cardiac arrest is effective in guiding resuscitation and may identify the etiology of PEA arrest.2.For decompensating acute type A aortic dissection, controlled pericardiocentesis may be a life-saving temporizing intervention in restoring hemodynamic stability before definitive treatment.3.ED transesophageal echocardiography has significant usefulness in guiding cardiac arrest resuscitations and identifying cardiac pathology. Financial/nonfinancial disclosures: None declared. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met. Additional information: The videos can be found in the Supplemental Materials section of the online article. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI4YTM5Yzc5NTE0YWY4ZWIzY2UxZDYyNDlmZGQ1YjBkNSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4ODAyMjQyfQ.dGsrF9OD4sCy6LUnbOmeoXUoZ0155zllaVttYXYMIvqV6d8r1GkX5V8IZAh4MH6-CE8uwyKSveySqze9WZIRdnMIiSQD1-Sr5TwP3SRar3qm1YAFAi0dDb1HWP1h2FXbbmcQCPXDKxRO20jrh73nKs6BOjpzw5asOXTejZ1nuUkQU8Deb3JCH5DK86uuQIGT7rrC40oH3tZv622F4HcNKk6gdBCWGXqq_Xs8p7Td0eT3HnXVQw55IQeOGG9HR-m9KbXifs4LqDzyUMrX2LO26pwV6NEmDyVgadLUW6qUgreuaiPKYoSixeSWaYXdSMlfFStuJzBwsJEhli1w7a1rPw Download .mp4 (1.09 MB) Help with .mp4 files Video 1Subxiphoid view showing circumferential pericardial effusion with right ventricular collapse.eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI1ZGE3MjkxZGI2ZjExN2QzNWVlZmY2MDVhYTljZjc5NiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4ODAyMjQyfQ.SfHz4xBmz0yg0Ub93W2cMMevOabVE_dK0TUV2p34g9j68G-YJ_Eiv6wD1TSm9Xf5-UIkuPW__oI4tc184ieyc7gqrIsHm8fkuiGtBemxbn2vmL0GcDUPDmxbYUe5YB3Db658YN7vscLWbyh16JUBNZpCyeHithuWIc8aVgWJMn3sric38myJLJnJF85rxZtGdVUrQBMpeH9EIxGGU2-2k1XfM9o1Os4xbMAtMCaGLWDSn6DO2wJPUxuRgRJp2TWhlkdoCEP_ypNf3PjlkK3QYdoSabIdiNIwlp86hT_zhGaw5NT9qLLNX5_OLdSuNU7yu4rBQwrgOXygFXmb-ZZh_Q Download .mp4 (1.42 MB) Help with .mp4 files Video 2Transesophageal echocardiography with aortic dissection flap.eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJlM2U4MmZkYWY1M2RkMmYwMzA2YTUwZjMyMTZlNjRiNCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4ODAyMjQyfQ.f9qDyl-6nH6f-q9FfztTUqgpOUvtXa2OxlUQXztlmMBId3LLwf5hF1SUnYp8_npSWtmrnRpzeerRJked6NsZZc5bFPOAxa45j8Q9YoB_oXY74qUdg4JWNuCSUJDqO7EUfyTVxeunG4BMMpj7WlFO0H4uuJJMx9DEeu8H6q_YinnXUdU8lLrJqkneNsdlOYaLz5SM5QHrZuyGNkWJ1C3M8giVmoJgdfF6yUw3XTR4wZa_pbRfp25bRkZOF4c40aFaNeh5IjWvoTII1eB7uoBDjwGgTcqoxhmBPOoE3DlWlf3yZfPdLbswIa8nnLgAlHbS1gv446KX3TTWD70oUmRb2A Download .mp4 (1.31 MB) Help with .mp4 files Video 3Long axis view of the aorta with dissection flap.eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0ZjA1ZTM2OTBlMjNlMjI0MGFkNTVlNzM1ZWU2NTkwMyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4ODAyMjQyfQ.YxW6oZuMBuIbmO_Oj4GU4u1LEwtp2lWTPna3-6o0aN9DtF59T4xpoLMBWN1kzhJCV1sFPvdATcqPLFUWxvk0-5zeKlM_p5E5r-YnJrfAa10PwOxMMo8bl29d3qzev1Pvy33oRcyHP4iW70NIsY-vff9PP0qwglaXV4kqvUyS3wCuvXYp0GyHZEhItDa6E90uXrvqT_MWf7KSzFpKAPD1s0q_UH3B2q5yKFJwaSzoUzSft2R1KF22eVycAR8apBUAfKKui5t99knoeGlECFFHLfotheFurHIWhgkVUZ4JnHiW6PVGU6SRStOT6F6ltyaKVQN9SCuP8SF_5Vff7gL7YA Download .mp4 (1.31 MB) Help with .mp4 files Video 4Short axis view of the aorta with dissection flap.eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiIxYjQzOTMyZmE2NDM3MGJhYWI5NzFhMDk2ZTNkMWViZSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4ODAyMjQyfQ.gRdBjS0_vF27o15fFAQefZWX_V_JTpCLNA-9DQsECDs3IinMXPCipwZg9ddSsPjJmDt5i1a7bHZuERbbZCDyqS_3sokP45RDqtLLMLsUL-0cdkZZLu6HejNMiMqnq6C6qgUNEkULpea4KJlvF6sqC8y8PcN0auVSiHEPvr07C6AdckMVUqYiRNpJ_y8-e6Le8bixCb2kRDMFh0oKnU3esE4o1nMLBA16ABoV2gHDlgP-efLhiFupwwexYx2qpV_t53UHkVCELMdf1zPrBD1Hm8p356vd8xjNXCMlWtCWj7hFnVWLSpwhCMF8rCArjd3DQhmU2WD5qLVwqpRV07J2vw Download .mp4 (54.09 MB) Help with .mp4 files Narration Video

SESSION TITLE: Monday Electronic Posters 2 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: The use of ketamine infusion for analgosedation in the medical intensive care unit (MICU) has historically been an uncommon practice. However, interest in its use has increased in recent years due to its unique pharmacologic properties that appear to make the drug ideally suited to this purpose. However, sparse data on the safety and efficacy of this practice continues to limit its widespread adoption. This study assessed the impact of continuous ketamine infusion on requirements for other concomitant analgosedative and vasopressor agents. METHODS: This was a single-center retrospective study of patients who received continuous infusion of ketamine to facilitate mechanical ventilation in the MICU between May 1, 2015 and September 1, 2018. Infusion rates of other analgosedative and vasopressor agents, as well as Richmond Agitation and Sedation Scores (RASS), were collected at the time of ketamine initiation and at 12, 24, and 48-hour intervals thereafter. RESULTS: Of the 81 ketamine infusion patients screened, 60 met inclusion criteria for the analysis of vasopressor infusion rates, and 41 were included in the analysis of RASS and concomitant analgosedative infusion rates after excluding 19 patients who were receiving neuromuscular blockade. There was a prominent trend towards decreased requirements for other analgosedative agents following the introduction of ketamine infusion. This reached statistical significance for total number of analgosedative infusions running (n=41) at 24 hours (-22%; p=0.03) and 48 hours (-32.6%; p=0.003), propofol infusion rate (n=14) at 12 (-53.3%; p=0.006), 24 (-56.3%; p=0.005), and 48 hours (-75.2%; p=0.001), and fentanyl infusion rate (n=14) at 12 (-20.9%; p=0.05), 24 (-35.4%; p=0.009), and 48 hours (-58.2%; p=0.0005). These dose reductions were accomplished without a significant change in the percentage of RASS scores within goal range (-1 to +1) at each time point. In addition, ketamine initiation was followed by a trend towards reduced vasopressor requirements which reached statistical significance for norepinephrine infusion rate (n=23) at 48 hours (-76%; p=0.006). CONCLUSIONS: Despite small sample size, the initiation of ketamine infusion for analgosedation in MICU patients was associated with significantly decreased requirements for other concomitant analgosedative and vasopressor agents without impacting time within RASS goal. However, retrospective design and lack of a comparison group were major limitations to our study. Future studies are needed to assess these findings in a prospective randomized fashion. CLINICAL IMPLICATIONS: This study supports the use of ketamine infusion for analgosedation in mechanically ventilated MICU patients. Its use is linked with decreased requirements for other concomitant analgosedative and vasopressor agents. These findings may lead to the more frequent use of ketamine infusion for analgosedation in the MICU. DISCLOSURES: No relevant relationships by Michael Cardone, source=Web Response No relevant relationships by Bruce Doepker, source=Web Response No relevant relationships by Gregory Eisinger, source=Web Response No relevant relationships by Jessica Elefritz, source=Web Response No relevant relationships by Matthew Exline, source=Web Response No relevant relationships by Matthew Huang, source=Web Response No relevant relationships by Jennifer McCallister, source=Web Response

An 88-year-old man with history of wet macular degeneration presented with painless vision loss in his right eye. He had awoken with a central scotoma without other associated ocular or systemic symptoms. Visual acuity in the affected eye was light perception only, and the remainder of his ophthalmic and neurologic examination results were noncontributory, although his fundi were poorly visualized. Bedside ocular ultrasonography was performed for further assessment (Figure). Acute submacular hemorrhage. Bedside ultrasonography revealed elevation of the macular retina, with underlying thin hypoechoic fluid collection. Dilated funduscopic examination showed a corresponding large area of submacular hemorrhage. Submacular hemorrhage is a common cause of painless vision loss in patients with age-related macular degeneration. Diagnosis is typically made on funduscopic examination, which is difficult to perform reliably without the use of cycloplegic agents. Bedside ultrasonography can be helpful in identifying elevation of the retina caused by bleeding from the neovascularized choroid, although the sensitivity and specificity have not been reported.1Stanescu-Segall D. Balta F. Jackson T.L. Submacular hemorrhage in neovascular age-related macular degeneration: a synthesis of the literature.Surv Ophthalmol. 2016; 61: 18-32Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar, 2Lorente-Ramos R. Arman J. Munoz-Hernandez A. et al.US of the eye made easy: a comprehensive how-to review with ophthalmoscopic correlation.Radiographics. 2012; 32: 175-200Crossref PubMed Scopus (29) Google Scholar Similar features may also be observed with subretinal hemorrhage in pediatric patients presenting with nonaccidental head trauma.3Riggs B.J. Trimboli-Heidler C. Spaeder M.C. et al.The use of ophthalmic ultrasonography to identify retinal injuries associated with abusive head trauma.Ann Emerg Med. 2016; 67: 620-624Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar The differential diagnosis for these sonographic findings includes conditions such as retinal tumors, making the clinical context very important.2Lorente-Ramos R. Arman J. Munoz-Hernandez A. et al.US of the eye made easy: a comprehensive how-to review with ophthalmoscopic correlation.Radiographics. 2012; 32: 175-200Crossref PubMed Scopus (29) Google Scholar Early diagnosis and referral to ophthalmology may lead to improved visual outcomes and identification of treatable neovascularization in the contralateral eye.1Stanescu-Segall D. Balta F. Jackson T.L. Submacular hemorrhage in neovascular age-related macular degeneration: a synthesis of the literature.Surv Ophthalmol. 2016; 61: 18-32Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar Our patient consulted with ophthalmology the following day to begin intravitreous injections of the vascular endothelial growth factor inhibitor aflibercept.

SESSION TITLE: Student/Resident Case Report Poster - Critical Care I SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Serotonin syndrome is an adverse drug reaction that results in mental status changes, autonomic and neuromuscular dysfunction1,2 due to excessive activation of post synaptic serotonin receptors. Fentanyl is a common ICU medication that is potentially under recognized as a contributor to this syndrome. CASE PRESENTATION: A 42 year old male with a past medical history of subglottic tracheal stenosis and post-traumatic stress disorder presented with a two day history of progressive dyspnea and was admitted for elective tracheostomy. During his admission, patient had acute respiratory failure, requiring emergent tracheostomy. Due to extensive scarring, the patient was left with an unfinished tracheal stoma, with a temporary tube, and was transferred to the MICU. No inhalational anesthetics were utilized during tracheostomy. Due to his difficult airway, delirium, agitation, and anxiety, heavy sedation was required to maintain ventilation. He was difficult to sedate due to morbid obesity and tolerance to opiates and benzodiazepines. As such, the patient was started on Fentanyl drip, in addition to Versed, Propofol, and Precedex drips. Of note, the patient’s home Paxil had been continued on admission. The day following titration of Fentanyl to 300mcg/kg/h, patient became diaphoretic, hyperthermic, tachycardic, hypertensive, and exhibited bilateral mydriasis, tremors and clonus. Septic workup was initiated and found to be negative. Serotonin syndrome was diagnosed using Hunter’s criteria. Fentanyl and Paxil were discontinued, supportive care initiated, and Cyproheptadine was started, after which the patient had resolution of symptoms. DISCUSSION: Significant morbidity and mortality can result from serotonin syndrome including acute encephalopathy, rhabdomyolysis, renal failure and cardiac arrest.2 Fentanyl, a medication commonly used for pain management and sedation can precipitate serotonin syndrome, especially when combined with another serotonergic agent. These cases are still relatively rare and under recognized.3 Hunter’s Criteria1 are the most sensitive and specific criteria for clinical diagnosis and include: spontaneous and inducible clonus, agitation, diaphoresis, ocular clonus, tremor and hyperreflexia, hypertonia, and temperature exceeding 38°C. CONCLUSIONS: Serotonin syndrome can mimic sepsis, neuroleptic malignant syndrome, malignant hyperthermia, and cholinergic toxicity and should be kept on the differential for patients receiving serotonergic medications. Reference #1: Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003; 96:635-642 Reference #2: Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol 2005; 28:205-214 Reference #3: Koury KM, Tsui B, Gulur P. Incidence of serotonin syndrome in patients treated with fentanyl on serotonergic agents. Pain Physician 2015; 18:E27-30 DISCLOSURE: The following authors have nothing to disclose: Mena Botros, Karen Wood, Yihenew Negatu, Corey Blum, Gregory Eisinger No Product/Research Disclosure Information