Intermediate-Risk and High-Risk Pulmonary Embolism: Recognition and Management: Cardiology Clinics: Cardiac Emergencies.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death. Every specialty of medical practitioner will encounter PE in their patients, and should be prepared to employ contemporary strategies for diagnosis and initial risk-stratification. Treatment of PE is based on risk-stratification, with anticoagulation for all patients, and advanced modalities including systemic thrombolysis, catheter-directed therapies, and mechanical circulatory supports utilized in a manner paralleling PE severity and clinical context.

Thrombus or tumor? A case report of a rare sarcoma entity: intimal sarcoma of the pulmonary arteries.

BACKGROUND: Tumor embolism is a very rare primary manifestation of cancers and the diagnosis is challenging, especially if located in the pulmonary arteries, where it can mimic nonmalignant pulmonary embolism. Intimal sarcoma is one of the least commonly reported primary tumors of vessels with only a few cases reported worldwide. A typical location of this malignancy is the pulmonary artery. Herein, we present a case report of an intimal sarcoma with primary manifestation in the pulmonary arteries. A 53-year-old male initially presented with dyspnea. On imaging, a pulmonary artery embolism was detected and was followed by thrombectomy of the right ventricular outflow tract, main pulmonary artery trunk, and right pulmonary artery after ineffective lysis therapy. Complementary imaging of the chest and abdomen including a PET-CT scan demonstrated no evidence of a primary tumor. Subsequent pathology assessment suggested an intimal sarcoma further confirmed by DNA methylation based molecular analysis. We initiated adjuvant chemotherapy with doxorubicin. Four months after the completion of adjuvant therapy a follow-up scan revealed a local recurrence without distant metastases. DISCUSSION: Primary pulmonary artery intimal sarcoma (PAS) is an exceedingly rare entity and pathological diagnosis remains challenging. Therefore, the detection of entity-specific molecular alterations is a supporting argument in the diagnostic spectrum. Complete surgical resection is the prognostically most important treatment for intimal cardiac sarcomas. Despite adjuvant chemotherapy, the prognosis of cardiac sarcomas remains very poor. This case of a PAS highlights the difficulty in establishing a diagnosis and the aggressive natural course of the disease. CONCLUSION: In case of atypical presentation of a pulmonary embolism, a tumor originating from the great vessels should be considered. Molecular pathology techniques support in establishing a reliable diagnosis.

Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Department.

BACKGROUND COVID-19 increases the risk of acute cardiovascular diseases (CVDs), including acute coronary syndrome (ACS), acute pulmonary embolism (APE), and acute myocarditis (AMyo). The actual impact of CVDs on mortality of patients with COVID-19 remains unknown. This study aimed to determine whether CVDs influence the course of COVID-19 pneumonia and if they can be easily detected by using common tests and examinations. MATERIAL AND METHODS Data of 249 consecutive patients with COVID-19 hospitalized in a dedicated cardiology department were analyzed. On admission, clinical status, biomarkers, computed tomography, and bedside echocardiography were performed. RESULTS D-dimer level predicted APE (AUC=0.850 95% CI [0.765; 0.935], P<0.001) with sensitivity of 69.4% and specificity of 96.2% for a level of 4968.0 ng/mL, and NT-proBNP predicted AMyo (AUC=0.692 95% CI [0.502; 0.883], P=0.004) and showed sensitivity of 54.5%, with specificity of 86.5% for the cut-off point of 8970 pg/mL. Troponin T levels were not useful for diagnostic differentiation between CVDs. An extent of lung involvement predicted mortality (OR=1.03 95% CI [1.01;1.04] for 1% increase, P<0.001). After adjusting for lung involvement, ACS increased mortality, compared with COVID-19 pneumonia only (OR=5.27 95% CI [1.76; 16.38] P=0.003), while APE and AMyo did not affect risk for death. CONCLUSIONS D-dimer and NT-proBNP, but not troponin T, are useful in differentiating CVDs in patients with COVID-19. ACS with COVID-19 increased in-hospital mortality independently from extent of lung involvement, while coexisting APE or AMyo did not.

[When to suspect pulmonary embolism: a balancing act]. / Wanneer moet je aan een longembolie denken?

Pulmonary embolism (PE) is a common disease, which can present with a variety of symptoms. Optimal use of diagnostics is challenging given the tight and delicate balance between underdiagnosis and over-testing or overdiagnosis. Diagnostic delay occurs in a substantial part of patients, and seems more common in those with known cardiopulmonary disease or non-specific signs and symptoms. At the other end of the spectrum, the amount of diagnostic imaging increases. Increased use of diagnostic imaging in general leads to more harmful exposures and might result in overtreatment, as may be the case in subsegmental PE. Correct use of clinical prediction rules reduces the need for diagnostic imaging while PE can still be ruled out safely. This clinical lesson describes three cases of PE and provides an overview of factors that contribute to underdiagnosis or overdiagnosis. We provide recommendations to improve our balancing act for this challenging disease.

Design and validation of algorithms to identify venous thromboembolism in the French National Healthcare Database.

PURPOSE: This paper aims to introduce an algorithm designed to identify Venous Thromboembolism (VTE) in the French National Healthcare Database (SNDS) and to estimate its positive predictive value. METHODS: A case-identifying algorithm was designed using SNDS inpatient and outpatient encounters, including hospital stays with discharge diagnoses, imaging procedures and drugs dispensed, of French patients aged at least 18 years old to whom baricitinib or Tumor Necrosis Factor Inhibitors (TNFi) were dispensed between September 1, 2017, and December 31, 2018. An intra-database validation study was then conducted, drawing 150 cases identified as VTE by the algorithm and requesting four vascular specialists to assess them. Patient profiles used to conduct the case adjudication were reconstituted from de-identified pooled and formatted SNDS data (i.e., reconstituted electronic health records-rEHR) with a 6-month look-back period prior to the supposed VTE onset and a 12-month follow-up period after. The positive predictive value (PPV) with its 95% confidence interval (95% CI) was calculated as the number of expert-confirmed VTE divided by the number of algorithm-identified VTE. The PPV and its 95% CI were then recomputed among the same patient set initially drawn, once the VTE-identifying algorithm was updated based on expert recommendation. RESULTS: For the 150 patients identified with the first VTE-identifying algorithm, the adjudication committee confirmed 92 cases, resulting in a PPV of 61% (95% CI = [54-69]). The final VTE-identifying algorithm including expert suggestions showed a PPV of 92% (95% CI = [86-98]) with a total of 87 algorithm-identified cases, including 80 retrieved from the 92 confirmed by experts. CONCLUSION: The identification of VTE in the SNDS is possible with a good PPV.

Prediction of mortality in acute pulmonary embolism in cancer-associated thrombosis (MAUPE-C): derivation and validation of a multivariable model.

Optimal risk stratification of patients with cancer and pulmonary embolism (PE) remains unclear. We constructed a clinical prediction rule (CPR) named 'MAUPE-C' to identify patients with low 30 days mortality. The study retrospectively developed and internally validated a CPR for 30 days mortality in a cohort of patients with cancer and PE (both suspected and unsuspected). Candidate variables were chosen based on the EPIPHANY study, which categorized patients into 3 groups based on symptoms, signs, suspicion and patient setting at PE diagnosis. The performance of 'MAUPE-C' was compared to RIETE and sPESI scores. Univariate analysis confirmed that the presence of symptoms, signs, suspicion and inpatient diagnosis were associated with 30 days mortality. Multivariable logistic regression analysis led to the exclusion of symptoms as predictive variable. 'MAUPE-C' was developed by assigning weights to risk factors related to the ß coefficient, yielding a score range of 0 to 4.5. After receiver operating characteristic (ROC) curve analysis, a cutoff point was established at ≤ 1. Prognostic accuracy was good with an area under the curve (AUC) of 0.77 (95% CI 0.71-0.82), outperforming RIETE and sPESI scores in this cohort (AUC of 0.64 [95% CI 0.57-0.71] and 0.57 [95% CI 0.49-0.65], respectively). Forty-five per cent of patients were classified as low risk and experienced a 2.79% 30 days mortality. MAUPE-C has good prognostic accuracy in identifying patients at low risk of 30 days mortality. This CPR could help physicians select patients for early discharge.

Obstructive cardiac myxosarcoma of the right ventricular outflow tract with pulmonary embolism and concurrent right atrial hemangiosarcoma in a dog.

A 13-year-old spayed female rottweiler crossbreed dog was presented with an 8-day history of abnormal gait and collapse associated with excitement or physical activity. A cardiac gallop was noticed on thoracic auscultation, and a 1st-degree atrioventricular block and sinus tachycardia were noted on an electrocardiogram. Echocardiography identified a hypoechoic, irregularly marginated luminal mass in the right ventricle at the level of the pulmonic valves. Postmortem gross examination confirmed the presence of a soft, polypoid, and botryoid mass (9 × 3 × 3 cm) with a smooth and glistening surface attached to the endocardium of the right ventricular outflow tract and extending to the pulmonary artery. The histological findings were consistent with the diagnosis of myxosarcoma with pulmonary embolism. In addition, the dog in this report had a right atrial hemangiosarcoma and a cutaneous hemangioma unrelated to her clinical findings. Key clinical message: Cardiac myxosarcomas are very rare neoplasms in dogs and concomitant primary heart tumors of different histogenesis are even rarer in dogs. To the authors' knowledge, this is the first report of coexistent myxosarcoma and hemangiosarcoma in the heart of a dog. Cardiac myxosarcomas should be considered in the differential diagnosis of intracavitary heart masses associated with signs of cardiac obstruction and failure.

Myxosarcome cardiaque obstructif de la voie d'éjection du ventricule droit avec embolie pulmonaire et hémangiosarcome auriculaire droit concomitant chez un chien. Une chienne croisée rottweiler stérilisée âgée de 13 ans a été présentée avec une histoire de démarche anormale et d'effondrement associés à l'excitation ou à l'activité physique depuis 8 jours. Un galop cardiaque a été noté à l'auscultation thoracique, un bloc auriculo-ventriculaire du 1er degré et une tachycardie sinusale ont été notés à l'électrocardiogramme. L'échocardiographie a permis d'identifier une masse luminale hypoéchogène et irrégulièrement marginalisée dans le ventricule droit au niveau des valvules pulmonaires. L'examen macroscopique post-mortem a confirmé la présence d'une masse molle, polypoïde et botryoïde (9 × 3 × 3 cm) avec une surface lisse et brillante attachée à l'endocarde de la voie d'éjection du ventricule droit et s'étendant jusqu'à l'artère pulmonaire. Les résultats histologiques concordaient avec le diagnostic de myxosarcome avec embolie pulmonaire. De plus, la chienne dans ce rapport présentait un hémangiosarcome auriculaire droit et un hémangiome cutané sans rapport avec ses résultats cliniques.Message clinique clé :Les myxosarcomes cardiaques sont des néoplasmes très rares chez le chien et les tumeurs cardiaques primaires concomitantes d'histogenèse différente sont encore plus rares chez le chien. À la connaissance des auteurs, il s'agit du premier rapport de myxosarcome et d'hémangiosarcome coexistant dans le cœur d'un chien. Les myxosarcomes cardiaques doivent être pris en compte dans le diagnostic différentiel des masses cardiaques intracavitaires associées à des signes d'obstruction et d'insuffisance cardiaque.(Traduit par Dr Serge Messier).

The utility of the systemic immune inflammation and systemic inflammation response indices in suspected intermediate-risk pulmonary embolism.

AIM: To evaluate the utility of the systemic immune inflammation index (SII) and systemic inflammation response index (SIRI) in diagnosing pulmonary embolism (PE) in emergency medicine. METHODS: We retrospectively reviewed the data of patients who presented to the emergency department and underwent contrast-enhanced computed tomography pulmonary angiography for suspected PE between January 1 and December 31, 2021. In 81/168 patients, the diagnosis of PE was confirmed and in 87/168 it was rejected. The data were analyzed with receiver operating characteristic analysis and binary logistic regression analysis. RESULTS: Patients with PE had a higher white blood cell count (P<0.001), neutrophils (P=0.002), monocytes (P=0.013), neutrophil/lymphocyte ratio (P<0.001), SII (P<0.001), and SIRI (P<0.001), and a lower lymphocyte count (P=0.002). The SII had a sensitivity of 75.31% and a specificity of 71.26%, while the SIRI had a sensitivity of 82.72% and a specificity of 68.97%. Binary logistic regression analysis showed that the Wells score, D-dimer level, and SII independently influenced the diagnosis of PE. CONCLUSION: The SII and SIRI may be used to support the diagnosis of PE in the emergency department.

Differentiating electrocardiographic indications of massive and submassive pulmonary embolism: A cross-sectional study in Southern Iran from 2015 to 2020.

BACKGROUND: Although using electrocardiogram (ECG) for pulmonary embolism (PE) risk stratification has shown mixed results, it is currently used as supplementary evidence in risk stratification. This cross-sectional study aimed to assess and compare ECG findings of massive and submassive PE versus segmental PE. METHODS: This cross-sectional study included 250 hospitalized patients with a confirmed diagnosis of acute PE from 2015 to 2020 in Southern Iran. Demographic variables, clinical data, troponin levels, on-admission ECG findings, echocardiography findings, and ECG findings 24 h after receiving anticoagulants or thrombolytics were extracted. RESULTS: Patients diagnosed with submassive or massive PE exhibited significantly higher rates of right axis deviation (p = .010), abnormal ST segment (p < .0001), S1Q3T3 pattern (p < .0001), inverted T wave in leads V1-V3 (p < .0001), inverted T wave in leads V4-V6 (p < .0001), and inverted T wave in leads V1-V6 (p < .0001). In a multivariable model, inverted T wave in leads V1-V3, inverted T wave in leads V4-V6, pulse rate, and positive troponin test were the statistically independent variables for predicting submassive or massive PE. Furthermore, inverted T wave in leads V1-V3 (sensitivity: 85%, specificity: 95%, accuracy: 93%, AUC: 0.902) and troponin levels (sensitivity: 72%, specificity: 86%, accuracy: 83%, AUC: 0.792) demonstrated the best diagnostic test performance for discriminating submassive or massive PE from segmental PE. CONCLUSION: In addition to clinical rules, ECG can serve as an ancillary tool for assessing more invasive testing and earlier aggressive treatments among patients with PE, as it can provide valuable information for the diagnosis and risk stratification of submassive or massive PE.

Chronic Thromboembolic Pulmonary Hypertension.

This JAMA Insights discusses the symptoms, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension.

Circulating miR-let7a levels predict future diagnosis of chronic thromboembolic pulmonary hypertension.

Distinct patterns of circulating microRNAs (miRNAs) were found to be involved in misguided thrombus resolution. Thus, we aimed to investigate dysregulated miRNA signatures during the acute phase of pulmonary embolism (PE) and test their diagnostic and predictive value for future diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Microarray screening and subsequent validation in a large patient cohort (n = 177) identified three dysregulated miRNAs as potential biomarkers: circulating miR-29a and miR-720 were significantly upregulated and miR-let7a was significantly downregulated in plasma of patients with PE. In a second validation study equal expression patterns for miR-29a and miR-let7a regarding an acute event of recurrent venous thromboembolism (VTE) or deaths were found. MiR-let7a concentrations significantly correlated with echocardiographic and laboratory parameters indicating right ventricular (RV) dysfunction. Additionally, circulating miR-let7a levels were associated with diagnosis of CTEPH during follow-up. Regarding CTEPH diagnosis, ROC analysis illustrated an AUC of 0.767 (95% CI 0.54-0.99) for miR-let7a. Using logistic regression analysis, a calculated patient-cohort optimized miR-let7a cut-off value derived from ROC analysis of ≥ 11.92 was associated with a 12.8-fold increased risk for CTEPH. Therefore, miR-let7a might serve as a novel biomarker to identify patients with haemodynamic impairment and as a novel predictor for patients at risk for CTEPH.

Performance-based outcome measures for assessing physical capacity in patients with pulmonary embolism: A scoping review.

INTRODUCTION: Up to 50 % of patients surviving a pulmonary embolism (PE) report persisting shortness of breath, reduced physical capacity and psychological distress. As the PE population is heterogeneous compared to other cardiovascular patient groups, outcome measures for assessing physical capacity traditionally used in cardiac populations may not be reliable for the PE population as a whole. This scoping review aims to 1) map performance-based outcome measures (PBOMs) used for assessing physical capacity in PE research, and 2) to report the psychometric properties of the identified PBOMs in a PE population. METHODS: The review was conducted according to the Joanna Briggs Institute framework for scoping reviews and reported according to the PRISMA-Extension for Scoping Reviews guideline. RESULTS: The systematic search of five databases identified 4585 studies, of which 243 studies met the inclusion criteria. Of these, 185 studies focused on a subgroup of patients with chronic thromboembolic pulmonary hypertension. Ten different PBOMs were identified in the included studies. The 6-minute walk test (6MWT) and cardiopulmonary exercise test (CPET) were the most commonly used, followed by the (Modified) Bruce protocol and Incremental Shuttle Walk test. No studies reported psychometric properties of any of the identified PBOMs in a PE population. CONCLUSIONS: Publication of studies measuring physical capacity within PE populations has increased significantly over the past 5-10 years. Still, not one study was identified, reporting the validity, reliability, or responsiveness for any of the identified PBOMs in a PE population. This should be a priority for future research in the field.

The significance of B-type natriuretic peptide in predicting early mortality among pulmonary embolism patients, alongside troponin: insights from a multicentric registry.

BACKGROUND: Early mortality assessment in acute pulmonary embolism (PE) is crucial for treatment decisions. The role of natriuretic peptides in this context is debated. This study explores elevated B-type natriuretic peptide (BNP) levels, relative to the upper normal limit (UNL), predicting mortality in PE, comparing with troponin (Tn). METHODOLOGY: A multicenter PE registry analyzed predictive values for early mortality risk using BNP and Tn, based on proportional elevation to the UNL. Patients followed current PE guidelines. RESULTS: Among 1677 PE patients, BNP's AUC exceeded Tn for all-cause (0.727 vs. 0.614) and PE-related mortality (0.785 vs. 0.644), though nonsignificant. BNP's cutoff was 3.5 times UNL for both all-cause and PE-related mortalities; Tn cutoffs were 1.38 and 1.23 times UNL, respectively. CONCLUSION: Elevated BNP relative to UNL significantly predicts all-cause and PE-related mortality. While akin to Tn, BNP merits consideration in assessing acute PE risk, especially in intermediate-high-risk cases.

Deployment of a human-centred clinical decision support system for pulmonary embolism: evaluation of impact on quality of diagnostic decisions.

Pulmonary embolism (PE) is a serious condition that presents a diagnostic challenge for which diagnostic errors often happen. The literature suggests that a gap remains between PE diagnostic guidelines and adherence in healthcare practice. While system-level decision support tools exist, the clinical impact of a human-centred design (HCD) approach of PE diagnostic tool design is unknown. DESIGN: Before-after (with a preintervention period as non-concurrent control) design study. SETTING: Inpatient units at two tertiary care hospitals. PARTICIPANTS: General internal medicine physicians and their patients who underwent PE workups. INTERVENTION: After a 6-month preintervention period, a clinical decision support system (CDSS) for diagnosis of PE was deployed and evaluated over 6 months. A CDSS technical testing phase separated the two time periods. MEASUREMENTS: PE workups were identified in both the preintervention and CDSS intervention phases, and data were collected from medical charts. Physician reviewers assessed workup summaries (blinded to the study period) to determine adherence to evidence-based recommendations. Adherence to recommendations was quantified with a score ranging from 0 to 1.0 (the primary study outcome). Diagnostic tests ordered for PE workups were the secondary outcomes of interest. RESULTS: Overall adherence to diagnostic pathways was 0.63 in the CDSS intervention phase versus 0.60 in the preintervention phase (p=0.18), with fewer workups in the CDSS intervention phase having very low adherence scores. Further, adherence was significantly higher when PE workups included the Wells prediction rule (median adherence score=0.76 vs 0.59, p=0.002). This difference was even more pronounced when the analysis was limited to the CDSS intervention phase only (median adherence score=0.80 when Wells was used vs 0.60 when Wells was not used, p=0.001). For secondary outcomes, using both the D-dimer blood test (42.9% vs 55.7%, p=0.014) and CT pulmonary angiogram imaging (61.9% vs 75.4%, p=0.005) was lower during the CDSS intervention phase. CONCLUSION: A clinical decision support intervention with an HCD improves some aspects of the diagnostic decision, such as the selection of diagnostic tests and the use of the Wells probabilistic prediction rule for PE.

Discrimination of the acute pulmonary embolism subtypes based on the novel MAPH score.

Acute pulmonary embolism (APE) is a thromboembolism situation that can be central or peripheral. APE risk analysis and classification are essential for therapy planning. Our aim is to determine the novel MAPH score (including age, mean platelet volume (MPV), total protein, and hematocrit parameters) that can distinguish APE subtypes. Our retrospective cohort analysis includes 97 APE patients referred to the emergency medicine department who underwent pulmonary computed tomography angiography (CTA) in 24 h from 2020 to 2022. The hospital information system provided demographic, clinical, laboratory, and pulmonary CTA data. APE was classified into central (46 patients) and peripheral (51 patients) depending on the area of vascular involvement. The central APE group had higher hypertension (HT) (67.4%) and atrial fibrillation (AF) (39.1%) incidence than the peripheral APE group (all p values > 0.05). The central APE had higher total protein and platelet counts (p = 0.003 and p = 0.036), but peripheral APE had higher troponin values (p = 0.029). Central APE had 2.17 ± 0.85 MAPH and peripheral APE 1.76 ± 0.95 (p = 0.029). HT, AF, platelet count, and MAPH score differed significantly in univariate logistic regression (all p values < 0.05). However, only platelet count varied in multivariate logistic regression (p = 0.042). ROC curve analysis revealed that the MAPH score predicts central APE with 83% sensitivity and 45% specificity at a cut-off level of 1.5. The new MAPH score as an indicator of blood viscosity may distinguish between central and peripheral APE. Our result is significant, especially for centers with limited examinations, as it may accelerate the diagnosis and treatment processes. We think that our results might guide future investigations.

A Novel Tool for Predicting an Abnormal Echocardiogram in Patients with Pulmonary Embolism: The PEACE Score.

BACKGROUND: Transthoracic echocardiography (TTE) is an essential tool for risk-stratifying patients with pulmonary embolism (PE), but its availability is limited, often requiring hospitalization. Minimal research exists evaluating clinical and laboratory criteria to predict lack of abnormal TTE findings. OBJECTIVE: We aimed to identify predictors associated with abnormal TTE results in patients with PE to potentially identify those safe for early discharge. METHODS: In this retrospective study, we analyzed an existing database of patients with venous thromboembolism (VTE) at two academic emergency departments, including adult patients with confirmed PE who underwent TTE. The primary goal was to develop and validate a score predicting abnormal TTE, defined as presence of one of the following: right ventricle (RV) dilatation or hypokinesis, septal flattening, right heart thrombus in transit, or ejection fraction < 50%. Variables were demographic characteristics, symptoms, computed tomography (CT) RV strain, troponin T, and N-terminal prohormone of brain natriuretic peptide (NTproBNP). Stepwise logistic regression was used to identify variables independently associated with abnormal TTE. Model discrimination was evaluated using area under the curve (AUC) of the receiver operating characteristic curve. A clinical prediction rule was developed. RESULTS: 530 of 2235 patients were included; 56% (297 of 530) had an abnormal TTE. The following six variables were independently associated with abnormal TTE: dyspnea, dizziness, troponin T ≥ 0.1 ng/mL, NTproBNP > 900 pg/mL, CT RV strain, and nonsubsegmental PE. A clinical prediction rule using these six criteria yielded scores between 0 and 7, performing well with AUC of 0.80 (95% CI 0.79-0.80). A score of 1 was 99.7% sensitive in identifying no abnormality. A score ≥ 5 was 98% specific for an abnormality. CONCLUSIONS: The PEACE (Pulmonary Embolism and Abnormal Cardiac Echocardiogram) criteria, composed of six variables, is highly effective in predicting abnormal TTE in patients with PE, potentially identifying who is safe for early discharge from the hospital.

Considerations for instituting pediatric pulmonary embolism response teams: A tool kit.

The incidence of pediatric pulmonary embolism (PE) has increased by 200 % in the last decade, but at a single center, it is still infrequent. Given the unique epidemiologic features of pediatric PE, diagnosis is often delayed, and the management is empiric, based on individual physician experience or preference. Thus, there is a strong need for center-specific uniform management of pediatric PE patients. In adults, the development of pulmonary embolism response teams (PERTs) or PE critical care pathways has shortened the time to diagnosis and the initiation of definitive management. Evidence to support an improvement in PE outcomes after the development of PERTs does not exist in children. Nonetheless, we have summarized the practical practice guidelines that physicians and institutions can adopt to establish their institutional PERTs or critical pathways. We also provide strategies for resource-challenged institutions for partnering with centers with expertise in the management of pediatric PE.