Metropolitan DC Thoracic Society Annual Meeting 2021 Abstract Competition

Introduction

Venous thromboembolism (VTE) currently affects 900,000 Americans annually, resulting in approximately 100,000 premature deaths.1 An associated right-sided heart thrombi is only detected in 4% of cases on echocardiogram but is thought to complicate 7-18% of VTE cases,2 and when present is associated with increased morbidity and mortality.3 Currently, there are no guidelines that specifically address the management of an acute pulmonary embolism with right heart thrombi (RHT). Here we present a case of an acute high-risk pulmonary embolism (PE) complicated by a RHT treated successfully noninvasively.

Case Presentation

A 66 year old female with a history of schizoaffective disorder and obstructive sleep apnea who presented from a psychiatric institution after being noted to be hypoxic with acute changes in mentation. On arrival, she was tachypneic, tachycardic and hypotensive requiring pressors. An arterial blood gas done showed pH 7.40, pCO2 30, pO2 99 on FiO2 0.36. Labs on admission showed an elevated D-dimer, lactic acid, white blood cell count and troponin I. Chest computed tomography (CT) angiography showed a large bilateral PE prior to ICU admission for acute high-risk PE. Echocardiogram showed severely impaired right ventricular systolic function and a mobile hypoechoic structure in the right atrium extending to the inferior vena cava. Lower limb ultrasound revealed a left lower extremity deep vein thrombosis. A multidisciplinary approach was taken and thrombolysis vs. surgical embolectomy was considered. Intravenous tPA was administered, she subsequently developed oral mucosal bleeding and was intubated for airway protection. CT head was unremarkable. After 24 hours, the bleeding stopped and repeated echocardiogram post tPA showed resolution of the right atrial thrombus. She was later discharged on apixaban for pulmonary outpatient follow-up.

Discussion

RHT is a rare but life threatening condition, as embolism to large structures can result in mortality of > 40%.2 While there is no consensus on management of RHT, therapeutic options include administration of heparin, thrombolytics, percutaneous and surgical thrombectomy. In a pooled analysis of 207 patients with RHT, the overall mortality was statistically lower (p=0.03) in the thrombolysis (18.2) and surgical embolectomy (18%) groups compared to anticoagulation alone (36.4%). However, there was no difference between the thrombolysis and thrombectomy (p = 0.9; OR, 0.98; 95% CI, 0.43–2.25).2 In patients with high-risk PE, mortality insignificantly trends toward higher mortality in surgery v.s. thrombolysis (47.4% v.s. 20.7%, p=0.1).2 This case highlights the clinical dilemma and feared complication of bleeding, highlighting the benefits and pitfalls of thrombolytic therapy.

References

1. CDC. Data and Statistics on Venous Thromboembolism | CDC. Centers for Disease Control and Prevention. Published February 12, 2020. Accessed September 7, 2020. https://www.cdc.gov/ncbddd/dvt/data.html 2. Burgos LM, Costabel JP, Galizia Brito V, et al. Floating right heart thrombi: A pooled analysis of cases reported over the past 10years. Am J Emerg Med. 2018;36(6):911-915. doi:10.1016/j.ajem.2017.10.045 3. Dalen JE. Free-Floating Right Heart Thrombi. Am J Med. 2017;130(5):501. doi:10.1016/j.amjmed.2016.11.041

Dwayne Nelson

Howard University Hospital, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine

Introduction Spontaneous pneumomediastinum (SPM) is a rare pathological condition in which air leaks into the mediastinum outside the trachea and esophagus. Common causes are trauma, iatrogenic, infection, interstitial lung disease, and excessive vomiting. A panic attack is a rare cause of SPM, and may present with nonspecific symptoms such as chest pain, dyspnea, and neck pain or discomfort.

Case report A 21-year-old Asian female with history of well-controlled exercise induced asthma came to ED with pleuritic chest pain, radiating to the neck which started during an argument This was associated with shortness of breath at rest that resolved with inhaler use, palpitation, sweating, fear of losing control and dizziness. On presentation to the ER, her respiratory rate was 18 breath per minute, with oxygen saturation maintained at 100% on room air. Her heart rate was ranging between 66 to 92 beats per minute. and her blood pressure was 103/60. Electrocardiography showed normal sinus rhythm with sinus arrhythmia. Complete blood count revealed mildly elevated white cell count of 10.89 x109/L with 7.66 x109/L neutrophils. C-Reactive protein was 1.0 mg/dl. Thyroid stimulating hormone was elevated to 5.588 mIU/ml with normal free T4 value of 0.98 ng/dl. ANA was negative. An erect anteroposterior chest radiograph (CXR) revealed air outlining the left mediastinal margin, and in the superior mediastinum on the lateral view suggestive of pneumomediastinum. A chest computed tomography (CT) angiography was consistent with pneumomediastinum without pulmonary embolism. Cardiothoracic surgery was consulted and she was treated with conservative therapy, namely high flow nasal cannula (HFNC) of 40 liters per minute and 100% oxygen. Her chest pain resolved on day two of admission. She was discharged and was followed up within a week with a repeat CXR which showed complete resolution of SPM.

Discussion SPM is a rare but benign condition for which up to 40% of causes is unknown. Notably, it usually does not require surgical intervention and can be managed conservatively with good prognosis, compared to esophageal rupture which may also present with a pneumomediastinum but carries up to 40% mortality. The use of conservative management such as oxygen therapy has been recommended for SPM; however HFNC has also been identified as a cause for pneumomediastinum. This case highlights a unique presentation of SPM and reinforces that it can be managed safely with conservative therapy, namely HFNC without extensive invasive procedures such as esophagography or surgery.

Consent Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal

References 1. Kouritas, V.K., et al. “Pneumomediastinum.” Journal of thoracic disease vol. 7,Suppl 1 (2015): S44-9. 2. Papadimos, J., et al. “Panic attack: An unusual cause of spontaneous pneumomediastinum.” International journal of critical illness and injury science vol. 4,1 (2014): 91-2. 3. Vogel SB, et al. Esophageal perforation in adults: aggressive, conservative treatment lowers morbidity and mortality. Ann Surg. 2005;241(6):1016-1023. doi:10.1097/01.sla.0000164183.91898.74 4. Bakhos, C.T., et al. “Spontaneous pneumomediastinum: an extensive workup is not required.” Journal of the American College of Surgeons vol. 219,4 (2014): 713-7. doi:10.1016/j.jamcollsurg.2014.06.001 5. Jafri, S., et al. High Flow Nasal Cannula Induced Subcutaneous Emphysema, Pneumomediastinum and Pneumothorax. American Journal of Respiratory and Critical Care Medicine. 193;2016:A5332.

Jin Yi

Howard University Hospital

Spontaneous Pneumomediastinum, SPM, Panic attack

Introduction: Subacute diffuse alveolar hemorrhage (DAH) is a rare entity that has been reported in primary, but not in drug-induced ANCA-associated vasculitis (AAV). Corticosteroids have been the mainstay therapy but accumulating evidence favors the use of rituximab as the primary steroid-sparing agent. Literature on drug-induced AAV is scarce given its low prevalence. Treatment is based on expert opinion and includes removing the offending agent and steroids. Case: A 62-year-old male with history of hypertension and diabetes presented with several months of fatigue and transfusion-dependent anemia of unknown etiology despite extensive evaluation. He presented to the hospital with two-weeks of fever and worsening dyspnea. He denied hemoptysis. The patient was diaphoretic, tachypneic, and had diffuse crackles on auscultation. He was hypoxemic, with an oxygen saturation of 85% on ambient air, which improved to 92% on 6L of oxygen. Chest computed tomography (CT) showed worsening widespread ground glass opacities (GGO) with a new focal area of consolidation (Figure 1A-C) compared to previous imaging done two months earlier. The patient was started on antibiotics without clinical improvement. Bronchoscopy with bronchoalveolar lavage (BAL) was consistent with DAH, and pathology demonstrated capillaritis with a mixed inflammatory infiltrate including neutrophils (yellow arrow, Figure 1D) with hemorrhage and hemosiderin-laden macrophages (black arrow, Figure 1D). Blood and bronchoscopy culture data was negative for bacterial and fungal infections, and broad respiratory viral panel was nonreactive including for SARS-coronavirus-2. Serum serologies demonstrated antinuclear antibodies 1:640, anti-histone antibodies, anti-PR3 antibodies, anti-myeloperoxidase antibodies, and anti-dsDNA antibodies. Extended myositis panel was nonreactive. Urine sediment showed red blood cell casts (black arrow, Figure 1E) and serum creatinine was elevated at 1.5 mg/dL. Treatment was initiated with prednisone 60 mg daily and rituximab (two one gram infusions separated by two weeks), with substantial improvement in symptoms and hypoxemia occurring within 48 hours. The patient had been started on hydralazine six months prior to the described presentation. Hydralazine was discontinued early on admission. The patient was discharged without supplemental oxygen on 40mg of prednisone. Repeat imaging four weeks after treatment showed significant radiological improvement (Figure 1F-H).

Discussion: This is the first report of a patient with hydralazine-induced AAV presenting with subacute DAH manifesting initially as transfusion-dependent anemia. Our case highlights the importance of CT expertise recognition and early BAL in the diagnosis of DAH, especially in patients with no history of hemoptysis, and it suggests effectiveness of rituximab for drug-induced AAV. Renal biopsy was not pursued given improvement of the creatinine.

Julio Huapaya

University of Maryland School of Medicine / National Institutes of Health

ANCA-associated vasculitis, diffuse alveolar hemorrhage, drug-induced ANCA-associated vasculitis, hydralazine, rituximab, steroids.

Abstract Introduction: Empyema Thoracis, pus in the pleural cavity, is a highly morbid condition and a rare complication of Mycobacteria fortuitum infection in immunocompetent adults.1-4

Case: We present the case of an immunocompetent 29-year-old African-American female who presented to the Emergency Department with worsening dyspnea on exertion, subjective fever, loss of appetite, weight loss of 10-15 pounds for one month and one day of severe left-sided chest pain with malaise and generalized body aches. She denied history of smoking, vaping, drug abuse, sick contacts and recent travel. Vitals were temperature: 102.9 F, heart rate: 140 beats/min, respiratory rate: 20 breaths/min, blood pressure: 115/75 mmHg, and O2 saturation: 100% on room air. Labs revealed mild leukocytosis and transaminitis. Chest imaging showed complete left lung opacification with rightward mediastinal shift on X-ray and a large, left hemithoracic fluid attenuated mass with mild wall thickening, suggesting empyema, on CT. Bedside ultrasound revealed significant loculations.

Management: A chest tube was placed, draining 2L of bloody, purulent fluid. WBC ~75855 and RBC~22000 noted on fluid analysis. The patient was admitted. Infectious Disease and Cardiothoracic Surgery were consulted. On hospital day two, chest X-ray showed no improvement and sputum culture started growing nontuberculous mycobacteria (NTM). Day four, the patient underwent Video-Assisted-Thorascopic Surgery (VATS) with conversion to thoracotomy without complications; two chest tubes (straight anterior and right-angled posterior) were placed for drainage. Post-VATS X-ray showed improving left upper lung aeration and stable chest tubes. Purulent drainage continued without significant events until day 11 when the patient became febrile. A genital tract infection due to foreign body was identified and Zosyn was changed to Linezolid for coverage. Day 13, bronchoscopy with BAL was negative for organisms. She received intrapleural Alteplase and Dornase-alpha for one week. Day 17 CT chest demonstrated a partially loculated left pleural collection (trapped lung), decreased in size, with improvement of airspace disease. At discharge, sputum cultures returned positive for M. fortuitum. The patient was unfortunately lost to follow-up.

Discussion: Empyema with trapped lung poses a therapeutic challenge. M. fortuitum is typically fast-growing and associated with cutaneous lesions in immunocompromised patients. This unique case of M. fortuitum presenting as a slow-growing pleural infection in an immunocompetent patient likely contributed to her late presentation with mild symptoms. This case emphasizes the need for prompt cardiothoracic surgery referral and suspicion of NTM in the absence of typical pathogens and unclear presentation of advanced empyema.

References 1. Hirabayashi R, Nakagawa A, Takegawa H, Tomii K. A case of pleural effusion caused by Mycobacterium fortuitum and Mycobacterium mageritense coinfection. BMC Infect Dis. 2019 Aug 15;19(1):720. doi: 10.1186/s12879-019-4366-8. PMID: 31416441; PMCID: PMC6694650. 2. Fabbian F, De Giorgi A, Pala M, Fratti D, Contini C. Pleural effusion in an immunocompetent woman caused by Mycobacterium fortuitum. J Med Microbiol. 2011 Sep;60(Pt 9):1375-1378. doi: 10.1099/jmm.0.024737-0. Epub 2011 Apr 1. PMID: 21459911. 3. Matsumoto T, Otsuka K, Tomii K. Mycobacterium fortuitum thoracic empyema: A case report and review of the literature. J Infect Chemother. 2015 Oct;21(10):747-50. doi: 10.1016/j.jiac.2015.05.012. Epub 2015 Jun 9. PMID: 26139179. 4. Anjum S, Tahir R, Pathan SA. Nontuberculous mycobacterial infection presenting as empyema and life threatening pneumothorax: A challenging situation in the emergency department. Qatar Med J. 2015 Jul 2;2015(1):8. doi: 10.5339/qmj.2015.8. PMID: 26535176; PMCID: PMC4614334.

Miranda Barnes

a. Medical Students, Howard University College of Medicine, Washington, DC b.Department of Internal Medicine, Howard University Hospital, Washington, DC c.Department of Pulmonary Medicine, Howard University Hospital, Washington, DC

Empyema, Nontuberculous Mycobacteria, Pleural Effusion, Pleural Infection, Parapneumonic Effusion, Video-Assisted Thorascopic Surgery, Thoracotomy, Immunocompetent, Mycobacteria fortuitum

INTRODUCTION: Dialysis disequilibrium syndrome (DDS) is a very rare complication of hemodialysis (HD), manifesting as a spectrum of neurologic features from cerebral edema (1). It classically occurs during first time dialysis after rapid removal of blood urea nitrogen (BUN) and is usually self-limiting(2). Here we present a severe DDS case in a known HD patient after two missed dialysis sessions.

CASE PRESENTATION: A 57-year-old Hispanic male with End Stage Renal Disease(ESRD) on HD and no known seizure disorder, presented to hospital for progressively worsening fatigue for one-month, associated with generalized weakness and two missed dialysis sessions. Laboratory investigations showed potassium 6.1meq/dL, urea 204mg/dl, creatinine 14.26mg/dl, pH 7.42, PaCO2 26mmHg, PaO2 106mmHg and HCO3 8mmol/L. He was given a hyperkalemic cocktail and dialysis was resumed immediately. During dialysis, the patient became tachycardic, hypoxic and had a seizure episode with no return to baseline mentation. Head CT and MRI were normal. CBC, Blood and urine cultures were negative. Electrolytes showed a decrease of urea from 204mg/dl to 124 mg/dl. A diagnosis of DDS was entertained based on drop in urea and absence of other causative factors. He was transitioned to the intensive care unit(ICU) for status epilepticus. Patient was eventually stabilized and had an uneventful transfer from the ICU and later discharged from the hospital to continue his routine HD schedule.

CONCLUSION: Severe DDS has become a rare “vanishing” entity owing to the improvements in modes of dialysis (3). In our index case, consecutive missed dialysis with elevated urea, intracerebral acidosis followed by rapid urea removal resulting in transient cerebral edema which culminated into the severe presentation. The case describes an unusual presentation of severe DDS in a known HD patient that only missed 2 sessions. It is important to be able to recognize this diagnosis and people at risk, because early detection and prevention can limit the serious morbidity and mortality associated with DDS.

References: 1. Mistry K. Dialysis disequilibrium syndrome prevention and management. Int J Nephrol RenovascDis. 2019;12:69-77 2. Dalia T, Tuffaha AM. Dialysis disequilibrium syndrome leading to sudden brain death in a chronichemodialysis patient. Hemodial Int. 2018 Jul;22(3):E39-E44. doi: 10.1111/hdi.12635. Epub 2018 Jan23. PMID: 29360280. 3. Murali KM, Mullan J, Roodenrys S, Hassan HC, Lambert K, Lonergan M. Strategies to improvedietary, fluid, dialysis or medication adherence in patients with end stage kidney disease on dialysis:A systematic review and meta-analysis of randomized intervention trials. PLoS One. 2019 Jan29;14(1):e0211479. doi: 10.1371/journal.pone.0211479. PMID: 30695068; PMCID: PMC6350978.

Mpey Tabot Tabot

Department of Medicine1, Division of Pulmonary and Critical Care2, Howard University Hospital

Background Asthma is a common disease, affecting about 10% of the world’s population. Status Asthmaticus (SE) is a medical emergency characterized by hypoxemia, hypercarbia, and secondary respiratory failure. There is a 10% mortality rate reported in ICU patients with SA (1). Beta-agonists, anticholinergics, and corticosteroids are the mainstay of therapy with either invasive or non-invasive ventilatory support. While most patients with SA can be managed with these interventions, a minority will have refractory SA. Here, we present a case of a patient with SA requiring extracorporeal membrane oxygenation (ECMO) support for SA management. Case A 27-year-old female with a history of asthma presented with worsening shortness of breath. The patient reported that her asthma had been well controlled on maintenance inhalers until 8 months ago when she lost health coverage. She was using the albuterol inhaler throughout the day due to increasing dyspnea. In the ED, she was tachypneic, sitting in a tripod position requiring bilevel positive pressure ventilation (BiPAP), and was started on continuous nebulization, magnesium sulphate, and solumedrol. Her initial workup showed hyperinflation on chest X-ray, which was otherwise unremarkable, and blood work only significant for a mildly elevated white cell count. The patient was intubated due to altered mental status and worsening respiratory acidosis on arterial blood gas. Neuromuscular blockade was administered for ventilatory compliance in the setting of severe obstruction. She had multiple episodes of dynamic hyperinflation that did not resolve with continuous albuterol nebulization, epinephrine, propofol, and ketamine drips, Terbutaline, paralytics, along with high-dose steroids. A trial of Sevoflurane was attempted without success. As she continued to have episodes of hemodynamic instability from dynamic hyperinflation, she was placed on ECMO. She improved while on ECMO and was decannulated 5 days later and discharged 4 days after decannulation. Discussion SA is a medical emergency that has a significant mortality rate when respiratory failure requiring mechanical ventilation occurs. This mortality is usually related to hemodynamic compromise from severe obstruction leading to dynamic hyperinflation and auto-PEEP. This phenomenon is recognized by rising peak and plateau pressures on the ventilator with associated hypotension and often necessitates transient disconnection from the ventilator and chest decompression. First-line therapies include beta-agonists, anticholinergics, corticosteroids, and magnesium sulfate. Propofol and Ketamine are sedatives of choice as they have bronchodilatory effects. In refractory cases, epinephrine infusion, medications like Terbutaline, and anesthetics like Sevoflurane can be attempted. ECMO can be considered in cases of SA refractory to all the above interventions (2). Placing the patient on ECMO allows for CO2 removal extracorporeal, allowing the patient to be on lower tidal volumes and therefore minimizing auto-PEEP while treating the obstruction. There are however significant complications associated with ECMO and patients who have a complication like hemorrhage have a higher mortality rate. ECMO outcomes in asthma overall are very good compared to ECMO use in other diseases with survival to discharge of over 80% (2). Conclusion ECMO as a rescue intervention in SA is a reasonable option with acceptable survival to hospital discharge. It should therefore be considered in refractory SA. References 1) Afessa B, Morales I, Cury JD. Clinical course and outcome of patients admitted to an ICU for status asthmaticus. Chest. 2001 Nov;120(5):1616-21. 2) Yeo, H.J., Kim, D., Jeon, D. et al. Extracorporeal membrane oxygenation for life-threatening asthma refractory to mechanical ventilation: analysis of the Extracorporeal Life Support Organization registry. Crit Care 21, 297 (2017). https://doi.org/10.1186/s13054-017-1886-8

Syed Nazeer Mahmood

MedStar Washington Hospital Center

Asthma, Status asthmaticus, ECMO

Introduction: Intensive rehabilitation is recognized as an essential component to successful outcomes for recovery after a major cardio-thoracic surgery. We developed a multi-modal rehabilitation program that combines a physical therapy protocol with neuromuscular electric stimulation and nutrition supplementation to achieve improved functional outcomes for patients requiring lung transplantation.

Methods: Patients are randomized to the treatment arm or usual care 72 hours after transplant. Both groups undergo a global assessment of functional capabilities prior to transplant and at 72 hours post-transplantation. Patients in the treatment arm received additional physical therapy plus therapy with an electrical device and nutrition supplementation with essential amino acids. All patients received computed tomography to measure change in lower extremity skeletal muscle area. Muscle cross sectional area was measured at 1/3rd of the distance from the femoral tuberosity to the knee articulation.

Results: Preliminary results for six patients are presented in Figure 1. All patients had decreases in muscle cross-sectional area at 14 days post transplant. Compared to the standard of care group, the treatment group decreased average time of intubation (1.00±0.0 vs 2.33±1.4 days), average ICU length of stay (6.33±4.2 vs 8.33±7.5 days), and average hospital length of stay (17.00±2.6 vs 23.30±9.0 days).

Conclusion: We intend to use the data obtained from this pilot study to develop a larger, randomized interventional trial evaluating the effects of an intense multimodal rehabilitation program in improving long-term patient outcomes (including patient and graft survival) in cardiothoracic transplant recipients and as well as hospital length of stay and rate of early re-admission.

Kadija Hersi

University of MAryland Medical Center, Baltimore,MD

INTRODUCTION: Coronavirus-2 disease 2019 (COVID-19) is a novelty virus that caused a worldwide pandemic. It can cause mild to critical illness requiring intensive care unit (ICU) admission. In the United States, Black and Hispanic individuals comprise a disproportionately high number of infections and deaths due to COVID-19, likely related to underlying social and healthcare disparities.1,2 There are limited studies identifying predictors of outcome among COVID-19,3 in minority patients. The aim of this study was to identify the predictors of mortality among laboratory confirmed COVID-19 minority patients with severe clinical disease admitted to the ICU.

METHODS: Clinical data at the time of ICU admission was extracted from electronic records for a total of 95 sequentially admitted patients to the medical ICU with confirmed COVID-19 diagnoses. Demographics, comorbidities, laboratory values that included inflammatory markers, ICU course, mortality and discharge status data were collected. The primary outcome was ICU mortality treated as a binary outcome. Summary characteristics were described based on survival status with a test of significance using ANOVA, kwallis and chi-square as appropriate. A univariate logistic regression was used to identify mortality predictor variables of statistical significance which were then included in a final multivariate regression model. Inflammatory markers were added individually to this finalized model to avoid collinearity. Findings were summarized using odds ratios and confidence intervals.

RESULTS: The mean (SD) age was 61.54(14) years, 34(36%) were men, 67(71%) were African Americans and 20 (16%) were Hispanic. Most common comorbidities were hypertension 55 (58%) and diabetes 46 (48%). Fifty-three (56%) were intubated, 23 (25%) required pressor support, and 15 (16%) patients had their initial blood culture positive. Inflammatory markers were elevated in most all patients which was associated with mortality. ICU mortality was 48% (45 patients). Univariate analysis identified age ≥ 65yrs (odds ratio [OR]=1.25; 95% CI,1.02-1.52; p= 0.032), higher SOFA scores of 2 and 3{ (OR=1.74, 95% CI ,1.05-2.89,p=0.035 ) and ( OR=1.90,95%CI,1.1-3.29; p=0.024 respectively)}, vasopressor use ( OR=1.77; 95%CI,1.44-2.18;p<0.001), severe ARDS (OR=;1.45;95%CI,1.05-2.01;p=0.027), mechanical ventilation use (OR=1.46;95%CI,1.22-1.79;p<0.001), procalcitonin>2.5ng/ml (OR=1.84;95% CI, 95%CI,1.03-3.29;p=0.042), ferritin>2000ng/ml (OR=1.45; 95% CI,1.12-1.89;p=0.007), CRP>20mg/dl (OR=1.67 OR=;95CI,1.3-2.13;p<0.001) and LDH>400 (OR=1.68;95%C,1.26-2.23;p<0.001) as predictors of ICU morality. Of these, only age ≥ 65yrs, mechanical ventilation and vasopressor use remained statistically significant independent predictors of mortality in multivariable regression model.

CONCLUSION Among predominantly minority patients with severe COVID-19 admitted to the ICU, older patients who become intubated, requiring vasopressor support and/or had elevated biomarkers of inflammation had a significantly higher ICU mortality.



REFERENCES: 1. Price-Haywood, E. G., Burton, J., Fort, D., & Seoane, L. (2020). Hospitalization and Mortality among Black Patients and White Patients with Covid-19. New England Journal of Medicine,382(26), 2534-2543. doi:10.1056/nejmsa2011686 2. Centers for Disease Control and Prevention. (2020). COVID-19 in Racial and Ethnic Minority Groups. Retrieved December 15, 2020, from https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/racial-ethnic-minorities.html 3. Cummings, M. J., Baldwin, M. R., Abrams, D., Jacobson, S. D., Meyer, B. J., Balough, E. M., Aaron, J. G., Claassen, J., Rabbani, L. E., Hastie, J., Hochman, B. R., Salazar-Schicchi, J., Yip, N. H., Brodie, D., & O'Donnell, M. R. (2020). Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. medRxiv : the preprint server for health sciences, 2020.04.15.20067157. https://doi.org/10.1101/2020.04.15.20067157

Lamiaa Rougui

Howard University Hospital, Washington, DC

COVID-19 infection, ICU mortality

Introduction Inhaled nitric oxide (iNO) transiently improves oxygenation in mechanically ventilated patients with acute respiratory distress syndrome without conferring improvements in clinical outcomes. Limited data exist regarding its effects in spontaneously breathing patients. We evaluated the effectiveness of continuous iNO administered via high-flow nasal cannula (HFNC) in COVID-19 respiratory failure. Methods We performed a multi-center observational cohort study of patients with respiratory failure from COVID-19 managed with HFNC. Patients were stratified by the administration of iNO via HFNC. Standard statistical comparisons and regression analyses were used to compare the need for mechanical ventilation and secondary endpoints including hospital mortality, length of stay, acute kidney injury, need for renal replacement therapy, and need for extracorporeal life support. Results 272 patients with COVID-19 were managed with HFNC and 66 (24.3%) of these patients received iNO via HFNC for a median of 88 hours (IQR: 44, 135). After 12 hours of continuous iNO, supplemental oxygen requirement was unchanged or increased in 52.7% of patients. Twenty-nine (43.9%) patients treated with iNO compared to 79 (38.3%) patients without iNO therapy required endotracheal intubation (P=0.47). After multivariable adjustment, there was no difference in need for mechanical ventilation between groups (OR: 1.53; 95% CI: 0.74-3.17), however, iNO administration was associated with longer hospital length of stay (IRR: 1.41; 95% CI: 1.31-1.51). No difference was noted between groups for hospital mortality, acute kidney injury, need for renal replacement therapy, or need for extracorporeal life support. Conclusion In patients with COVID-19 related respiratory failure, iNO delivered via HFNC did not result in reduced oxygen requirement in the majority of patients, nor was it related to improved clinical outcomes. Given the cost of continuous iNO and the observed association with increased length of stay, judicious selection of patients most likely to benefit from this therapy in this setting is warranted.

Abhimanyu Chandel <abhimanyu.chandel4@gmail.com>

Walter Reed National Military Medical Center

Purpose: Tracheostomy (trach) placement after lung transplantation (LTx) is occasionally required in patients with prolonged ventilator dependence. However, little research exists on potential predictors and outcomes for recipients with post-LTx trachs. We examined baseline characteristics and compared short and intermediate-term outcomes of patients with and without post-LTx trachs.

Methods: Baseline data, short and term-long outcomes from patient’s s/p LTx performed between 1/1/12 and 6/31/19 who required trach during the index hospitalization were evaluated and compared with the trach-free cohort.

Results: Compared to trach-free patients, the trach cohort patients were younger (51.6±13.6 vs. 56.9±10.8, p=0.034) and had a higher mean lung allocation score (LAS) (66.6±22.8 vs. 55.2±20.7, p=0.014). They were more likely to be inpatient at the time of LTx (54.2% vs 32.1%, p=0.035), had a bilateral LTx (60.8% vs 35.9%, p=0.001), and require extracorporeal life support (ECLS) pre- (16.7% vs. 1.9%, p=0.0005) and post-LTx (16.7% vs. 0.6%, p=0.001). Patients in trach cohort had longer mechanical ventilation (p=0.0001) and hospital length of stay (HLOS) (p=0.0001). More patients in the trach cohort required acute rehabilitation on discharge (p=0.0016). Although index in-hospital mortality of the trach cohort was higher (16.7% vs 2.5%, p=0.013), there was no difference in 1-year mortality (16.7% vs 8.3%, p=0.229) c/w trach-free cohort. Long term, there was a significantly reduced long-term survival in trach patients (Fig.1) with a limited follow-up.

Conclusion: LTx recipients requiring post-op trach appear to be sicker, as evidenced by a higher LAS and greater use of ECLS pre-LTx. Trach cohort had a longer duration of mechanical ventilation, post-op HLOS and discharge to acute rehabilitation. In our study, the need for post-LTx trach was associated with increased short-term mortality. Although one-year post-LTx mortality was similar between the groups, long-term survival was worse in trach cohort with larger and longer studies needed.

Anubhav Thapaliya

INOVA Fairfax Hospital, Advanced Lung Diseases & Lung Transplant Department

Pulmonology, Lung Transplant, Outcomes, Tracheostomy

Background: Spirometry is a functional study used to assess and diagnose lung disease in children. Current ATS/ERS acceptability guidelines for spirometry in preschool children include Back Extrapolation Volume (BEV) < 80ml or < 12.5% FVC and Exhalation Time (ET) ≥ 3 seconds. The age cut-off for the use of the modified criteria is 6 years. The objective of our study was to investigate the number of children above or below the cut-off that are actually able to meet these criteria.

Methods: We reviewed retrospectively spirometry performed by children 4 to 7 years-of-age in our laboratory over a 15 year period. The tests compared 4 age groups on two main criteria - BEV and ET -according to the patients’ age. Gender, race and underlying diagnosis were not taken into consideration.

Results: A total of 8,481 tests were analyzed. The vast majority of 4-year-olds could not meet the criteria of BEV < 80mL. The percentage of children who did not meet the criteria in the 5 to 7 year-old group was substantial but similar. The expiratory time was < 3 sec in 75% of the youngest children and gradually increased with increasing age.

Conclusion: Our results suggest that even the current criteria for acceptable effort in spirometry do not correspond with the actual ability of the patients asked perform these tests. Furthermore, the preschool criteria seem to be better suited for the older children (6 & 7-year-olds).

Jonathan Schroeder

Children's National Hospital

Pediatrics, Children, Lung Function, Spirometry, Physiology

Background: Influenza and pneumonia were 8th leading cause of death in year 2018. Since 1950, mortality rates in Hispanics populations either higher or like that of non-Hispanics populations. This mortality rates with geographic variations were documented in previous studies. We hypothesized that the geographic variation among Hispanics and non-Hispanics between different United States census and Health & Human Services (HHS) region and ethnic disparity persists.

Study design and methods: The CDC database for multiple cause of death between 1999-2018 for Hispanics and non-Hispanics decedents aged 25 to 84 years with an ICD-10 code for influenza (J09-J11) and pneumonia (J12-J18) was used. Age-adjusted mortality rates (AAMR) and 95% CI were computed by 2013 urbanization and ethnicity for HHS regions.

Results: In 1999-2018 combined at ages 25-84 years among Hispanic whites (HW) there were 136,321 mentions of IP on death certificates, of which 39,131 (28.7%) were coded as UCOD compared to 1,700,144 mentions in non-Hispanic whites (NHW) of which 466,230(27.4%) were UCOD

The UCOD crude death rate was significantly higher in Non-Hispanics than Hispanics at each ten-year age group 25-84 years.

Regions 2 and 9 showed greatest disparities.

HHS region 2 showed significantly higher mortality rates in Hispanics whites 21.78 (21.24- 22.33) 36.5% greater (p<0.05) than that in NHW of 15.71 (15.56-15.86) and more prominently in large metropolitan at a rate of 27.1 (26.36-27.83) as compared to 19.78 (19.47- 20.09) and micropolitan/ Non metro area

Similarly, in region 9, Hispanics had mortality rates almost as high as Non- Hispanics, mostly in Large metropolitan areas [15.7(95% CI15.4 - 16.0)] compared with non-Hispanic large metro 16.5 (95% CI 16.3 - 16.6). Also, similar trends in medium and small metropolitan areas.

Conclusion: This analysis of 1999-2018 mortality from influenza and pneumonia showed disparity in influenza and pneumonia mortality among Hispanics versus non-Hispanics. It’s exists and persists by HHS region and urbanization for years. The identification of biggest disparity in influenza and pneumonia mortality will assist policy maker to give more focus and proper distribution of resources including for the COVID-19 pandemic 

Mahbubur Sumon

1 Division of Pulmonary Medicine and Critical Care, Howard University Hospital and 2 Howard University College of Medicine, Washington, DC, USA

Rationale: Immune checkpoint inhibitors (ICIs) have become highly effective therapies for several cancer types. Research also suggests ICIs improve host defense during viral infection. However, ICIs can also produce autoimmune organ injury including pneumonitis. A critical question during the SARS-CoV-2 infection (COVID-19) pandemic has been whether prior ICI treatment worsens or improves outcomes with this virus. To address this issue, we performed a systematic review of studies of cancer patients with COVID-19 that provided data on prior ICI treatment, as well as patients not on ICIs, and provided patient outcomes. Methods: We performed a systematic search of PubMed, EMBASE, Scopus and the Web of Science for relevant citations of published studies as well as medRxiv and bioRxiv for prepublication citations through December 14, 2020, using individualized search strategies prepared for each database. A standardized data extraction form was utilized, and studies were included if they provided information on severity of disease, or mortality in patients with cancer presenting with COVID-19 that allowed within study comparison of patients who had received ICI therapy versus patients who have not. Studies were stratified based on whether they did or did not provide data allowing an assessment of the adjusted effects of ICIs on these outcomes. Results: After title, abstract, or full paper review of 16,587 retrieved reports, 34 met inclusion criteria and underwent analysis. Collectively, the studies included 7,177 total patients but only 436 (6%) had previously received ICI therapy. Twenty-three studies each included <10 patients who had received ICIs and only 3 included > 50 patients. The time between the last ICI treatment and COVID-19 presentation varied in studies from 4 to 820d. Thirty-one studies provided survival data. Across 24 studies presenting unadjusted data, ICI therapy had no significant effect on the overall odds ratio (95% CI) of survival [1.03 (0.81, 1.32)]. Of the 7 studies that provided adjusted outcome data, ICI therapy had effects on the survival OR that crossed the no effect line in 6, while one study did not. When combined in a random effects model, the overall OR with ICI therapy across these studies was also not significant [1.28 (0.44, 3.74)]. Twenty studies provided data on severe events. Across 15 studies that provided unadjusted data, ICI therapy was associated with a small increase in the OR of having a severe event [1.48 (1.06, 2.07)]. Five studies provided adjusted outcomes data for severe events that when combined in a random effects model the overall OR with ICI therapy was not significant [1.50 (0.44, 5.08)]. Conclusions: When examined across studies that provided data to analyze adjusted outcomes in cancer patients developing COVID-19 infection, prior ICI therapy did not appear to be associated with a worsened outcome. The overall reported experience with ICI treated cancer patients presenting with COVID-19 is small, and the number of studies providing adjusted data to assess the impact of ICIs on outcomes is even smaller. Additional study with larger and more detailed data bases is needed to determine whether prior ICI therapy alters outcomes in cancer patients presenting with COVID-19 infection.

Samuel Minkove

National Institutes of Health, Critical Care Medicine

Thoracic Oncology, Immune Checkpoint Inhibitors, COVID-19

Rationale: Immune stimulation with immune checkpoint inhibitors (ICIs) has emerged as a highly effective treatment for several cancer types. Research also suggests these agents may be therapeutic for viral infections. However, by interrupting inhibitory signaling pathways, ICIs can cause immune-related adverse events including pneumonitis. A critical question during the present SARS-CoV-2 pandemic has been whether prior ICI treatment aggravates or improves virus-associated lung injury. Methods: To address this question, we first developed a lethal coronavirus acute lung injury model in A/J mice by infecting them intratracheally (IT) with mouse hepatitis virus-1 (MHV-1), a betacoronavirus that can be studied at Biosafety Level-2 (Study-1). We then investigated the effects of anti-PD-L1 monoclonal antibody (anti-PD-L1mAb; clone 10F.9G2, Bio X Cell) pretreatment on outcomes with MHV-1 lung challenge (Study-2). Results: A/J mice were challenged with an LD50 IT dose of MHV-1 or as control, culture medium alone. Compared to controls who did not have any mortality, MHV-1 challenge in mice produced lethality beginning at 4 to 5d that continued up to 10d following infection, a pattern similar to unsupported patients with COVID-19. Over 240h, surviving mice receiving MHV-1 challenge had progressive hypoxia compared to controls at the same time points (p<0.001 at 240h). Consistent with initial innate and later adaptive lung immune responses, MHV-1 stimulated early increases in bronchial alveolar lavage (BAL) neutrophils at 48h (p<0.001) that then decreased at 240h (p=0.03), while BAL lymphocytes were most increased later at 240h (p=0.03). Notably, MHV-1 infection also produced significant increases in PD-L1 expression on lung CD-8 T-cells at 48 and 120h. Experiments in noninfected animals showed that compared to isotype-mAb (control) treatment, 4 doses of anti-PD-L1mAb (300μg/mouse) administered intraperitoneally every 3d significantly reduced lung immune cell PD-L1 expression (normalized mean fluorescence intensity, p=0.04) and produced anti-PD-L1mAb levels at 14d consistent with those measured in ICI-treated cancer patients ( 283.2 ± 112.4 μg/mL). Therefore, in Study 2, mice were treated with either isotype-mAb or anti-PD-L1mAb (300μg/mouse, every 3 days) starting 12d before and continuing until 3d after IT challenge with LD-50 IT doses of MHV-1. Across 3 initial experiments with 32 treated versus 32 controls, PD-L1mAb produced small decreases in survival that was not statistically significant (p =0.09). This was not observed in 4 subsequent confirmatory studies involving 61 treated versus 61 controls (p=0.23), and when combined across 7 studies, PD-L1mAb had no significant effect when comparing 93 treated versus 93 control animals (p=0.74) Conclusions: Intratracheal MHV-1 challenge in A/J mice produced lethality and late changes in circulating lymphocytes and lung lavage lymphocytes and protein that appear consistent with changes observed clinically with SARS-CoV2 infection. Prior treatment with anti-PD-L1mAb in this model had no significant effect on mortality when compared to controls.

Samuel Minkove

National Institutes of Health, Critical Care Medicine