Faculty Bibliography

OBJECTIVE:<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS:Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

PURPOSE/OBJECTIVE:The right ventricular outflow tract (RVOT) velocity time integral (VTI), an echocardiographic measure of stroke distance, correlates with cardiac index. We sought to determine the prognostic significance of low RVOT VTI on clinical outcomes among patients with acute pulmonary embolism (PE). MATERIALS AND METHODS/METHODS:We conducted a retrospective review of echocardiograms on Pulmonary Embolism Response Team (PERT) activations at our institution. The main outcome was a composite of death, cardiac arrest, or hemodynamic deterioration. RESULTS:Of 188 patients, 30 met the combined outcome (16%) and had significantly lower RVOT VTI measurements (9.0 cm v 13.4 cm, p < 0.0001). The AUC for RVOT VTI at a cutoff of 10 cm was 0.78 (95% CI 0.67-0.90) with a sensitivity, specificity, negative predictive value, and positive predictive value of 0.72, 0.81, 0.94, and 0.42, respectively. Fifty-two patients of the cohort were classified as intermediate-high-risk PE and 21% of those met the combined outcome. RVOT VTI was lower among outcome positive patients (7.3 cm v 10.7 cm, p = 0.02). CONCLUSIONS:Low RVOT VTI is associated with poor clinical outcomes among patients with acute PE.

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate-high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate-high-risk pulmonary embolism.

Objective: Pulmonary embolism response teams (PERTs)have become increasingly popular at institutions around the country, although only anecdotal evidence is available to support their efficacy. PERTs are mechanisms for rapid involvement of a multidisciplinary team in the management of a time-sensitive condition with many treatment options spanning multiple specialties. We aimed to evaluate time to management of pulmonary embolisms and outcomes since 2016 under our institution's PERT. Method(s): We retrospectively reviewed 151 patients with PERT activations since inception, collecting data on demographics, time to treatment, treatment modality, and in-hospital outcomes. Result(s): The average age was 62.4 years (range, 30-95 years), and 54% of patients were male; 39.4% of patients had normal echocardiographic recordings, with 27% showing right ventricular (RV)hypokinesis, 9.1% showing elevated pulmonary artery pressures, and 6.1% showing RV enlargement. Anticoagulation alone was received by 91.4% of patients; 4.5% had catheter-directed therapy (CDL), and 3.0% had systemic administration of tissue plasminogen activator (tPA). The average time to invasive intervention was 665 minutes (95% confidence interval [CI], 249-1080 minutes)for CDL and 22 minutes (95% CI, 0-456 minutes)for systemic tPA. Average time to anticoagulation was 3 minutes (95% CI, 154-160 minutes). For patients with echocardiographic findings suggestive of RV strain, 21.4% (95% CI, 0.04-0.51)had tPA or an invasive intervention. Of patients with echocardiographic findings consistent with RV strain who underwent conservative management, 80% were discharged home after an average length of stay of 6.0 days (95% CI, 4.5-7.5). Twenty (14.1%; 95% CI, 5.5-22.5)patients receiving anticoagulation alone had bleeding events, whereas none of the patients undergoing CDL or tPA had bleeding. Sixteen (11.2%; 95% CI, 5.7-16.3)patients who had anticoagulation died in the hospital or were discharged to hospice, and none of the patients receiving CDL or tPA died or were discharged to hospice. The odds of in-hospital death were lower for patients receiving anticoagulation than for those without (odds ratio, 0.29), suggesting appropriate identification of high-risk patients. Average hospital stay was 6.5 days (95% CI, 4.9-8.5)for patients who received anticoagulation, 5.3 days for CDL (95% CI, 0-11.2), and 8 days for tPA (95% CI, 2.6-13.4). Conclusion(s): We found that a dedicated PERT team leads to efficient delivery of care and excellent outcomes. The majority of pulmonary embolisms can be managed with anticoagulation alone. CDT and systemic tPA are safe adjunctive treatments for select patients.

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute PE, including both clinical data and consensus opinion to provide guidance for clinicians caring for these patients.

BACKGROUND:Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization. OBJECTIVE:The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution. METHODS:A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included. RESULTS:In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions.

BACKGROUND:Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS:We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS:Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS:Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.

BACKGROUND: The first changes associated with smoking are in the small airway epithelium (SAE). Given that smoking alters SAE gene expression, but only a fraction of smokers develop chronic obstructive pulmonary disease (COPD), we hypothesized that assessment of SAE genome-wide gene expression would permit biologic phenotyping of the smoking response, and that a subset of healthy smokers would have a "COPD-like" SAE transcriptome. METHODOLOGY/PRINCIPAL FINDINGS: SAE (10th-12th generation) was obtained via bronchoscopy of healthy nonsmokers, healthy smokers and COPD smokers and microarray analysis was used to identify differentially expressed genes. Individual responsiveness to smoking was quantified with an index representing the % of smoking-responsive genes abnormally expressed (I(SAE)), with healthy smokers grouped into "high" and "low" responders based on the proportion of smoking-responsive genes up- or down-regulated in each smoker. Smokers demonstrated significant variability in SAE transcriptome with I(SAE) ranging from 2.9 to 51.5%. While the SAE transcriptome of "low" responder healthy smokers differed from both "high" responders and smokers with COPD, the transcriptome of the "high" responder healthy smokers was indistinguishable from COPD smokers. CONCLUSION/SIGNIFICANCE: The SAE transcriptome can be used to classify clinically healthy smokers into subgroups with lesser and greater responses to cigarette smoking, even though these subgroups are indistinguishable by clinical criteria. This identifies a group of smokers with a "COPD-like" SAE transcriptome.