C-reactive Protein and Risk of Right Ventricular Dysfunction and Mortality in Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: Right ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE. METHODS: This cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis. RESULTS: The study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0-76.4]mg/L vs n=124, 45.4 [16.0-111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00-1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00-1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively. CONCLUSIONS: As an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE.

High-Sensitivity vs Conventional Troponin Cutoffs for Risk Stratification in Patients With Acute Pulmonary Embolism.

Importance: High-sensitivity troponin tests can detect even milder cardiac troponin elevations in plasma, beyond the threshold of conventional troponin tests. Whether detection of low-grade cardiac troponin elevation is associated with outcomes of patients with hemodynamically stable pulmonary embolism (PE) and helps with risk stratification is unknown. Objective: To determine the association between high-sensitivity cardiac troponin I (hs-cTnI) compared with conventional cardiac troponin I (cTnI) and PE risk designations according to the European Society of Cardiology (ESC) 2019 classification scheme and clinical outcomes in patients with hemodynamically stable PE. Design, Setting, and Participants: This is a post hoc analysis of data from the prospective Prognostic Value of Computed Tomography (PROTECT) multicenter cohort study enrolling patients from 12 hospital emergency departments in Spain. In this analysis, cTnI and hs-cTnI were compared with respect to ESC risk designation, and the association between troponin values and a complicated course after PE diagnosis was evaluated. Of 848 patients enrolled in PROTECT, 834 (98.3%) had hsTnI and cTnI values available and were included in the present analysis. Data were analyzed from May to December 2022. Exposures: Troponin blood testing with cTnI (threshold of >0.05 ng/mL) vs hs-cTnI (threshold of >0.029 ng/mL) assays at the time of PE diagnosis. Main Outcomes: Complicated course, defined as hemodynamic collapse, recurrent PE, or all-cause death, within 30 days after PE. Results: Of 834 patients (mean [SEM] age, 67.5 [0.6] years; 424 [50.8%] female), 139 (16.7%) had elevated cTnI and 264 (31.7%) elevated hs-TnI, respectively. During follow-up, 62 patients (7.4%; 95% CI, 5.7-9.4) had a complicated course. Analyzing troponin elevation as a binary variable, elevated cTnI (odds ratio [OR], 2.84; 95% CI, 1.62-4.98) but not hs-cTnI (OR, 1.12; 95% CI, 0.65-1.93) was associated with increased odds of a complicated course. Of 125 patients who had elevated hs-cTnI but normal cTnI, none (0; 95% CI, 0.0-2.9) developed a complicated course. Using the 2019 ESC risk stratification scheme, hs-TnI classified fewer patients as low risk compared with cTnI. Among 78 patients designated as ESC low risk when using cTnI but not with hsTnI, none (0; 95% CI, 0.0-4.6) had a complicated course. Conclusions and Relevance: In this study of patients with hemodynamically stable PE, hs-cTnI identified modest elevations in cardiac troponin levels. However, the results did not provide additive clinical value compared with cTnI. These findings suggest that use of hs-cTnI may result in overestimation of the risk in patients with stable PE.

National Early Warning Score-2 for Identification of Patients with Intermediate-High-Risk Pulmonary Embolism.

Consensus statements have proposed the use of the National Early Warning Score 2 (NEWS2) to identify stable patients with acute pulmonary embolism (PE) and an intermediate-high risk of adverse outcomes. We aimed to externally validate NEWS2 and compare it to another predictive score (Bova). Using NEWS2 (cutoff ≥5 and ≥7) and the Bova score (cutoff >4), we classified patients as intermediate-high risk (vs. non-intermediate-high risk), and we compared the test characteristics of these risk classification tools for a complicated course within 30 days after PE diagnosis. We also assessed the validity of NEWS2 for predicting a complicated course by adding the results of echocardiography and troponin testing to the model. Of the 848 enrolled patients, the NEWS2 score ≥5 classified 471 (55.5%) and the Bova score classified 37 (4.4%) as intermediate-high risk. NEWS2 had a significantly lower specificity for a 30-day complicated course than Bova (45.4 vs. 96.3%, respectively; p < 0.001). Using the higher score threshold (≥7), the NEWS2 classified 99 (11.7%) as intermediate-high risk, and the specificity was 88.9% (difference with Bova, 7.4%; p < 0.001). The proportion of patients with intermediate-high risk PE was 2.4% for the combination of a positive troponin testing and echocardiographic right ventricle dysfunction and a positive NEWS2 (score ≥7), while the specificity was 97.8% (difference with Bova, 1.5%; p = 0.07). Bova outperforms NEWS2 for predicting a complicated course among stable patients with PE. Addition of troponin testing and echocardiography improved the specificity of NEWS2, although it was not superior to Bova. CLINICALTRIALS.GOV NUMBER: : NCT02238639.

Pediatric Living Lung Donor Transplant Candidates: Psychiatric Status of Utilized and Non-Utilized Donors.

Living donor lung (lobar) transplantation has greatly decreased in the past decade due to the success of the lung allocation score (LAS) system, instituted in 2005 by the Organ Procurement and Transplantation Network (OPTN). Between 1993 and 2006, 460 living lung donor transplants were performed in the United States with 369 donations occurring at the University of Southern California and Washington University in St. Louis. These two centers accounted for over 80% of all living donor lung transplants between 1994 and 2006. All potential donors received a psychological/psychiatric evaluation as part of the donor selection process, which is standard practice in the United States, Europe, and Asia. Utilized and non-utilized lung donors were compared in terms of their psychiatric history and present status. Results indicated that 31% (N = 54) of the total sample had a lifetime prevalence of a psychiatric disorder, which is less than that the 46% lifetime rate for the general population (Kessler in Arch Gen Psychiatry 62:593-602, 2005). This study did find that psychiatric history or status was not exclusion factor for transplant surgery in either group. This observation about psychiatric issues in potential living lung donors should be useful to transplant centers who utilize adult live donors of any solid organ type for pediatric recipients and in Japan where live donor lung transplants still represent a significant proportion of lung transplants (Date in J Thorac Dis 8: S631-S636, 2016).

Randomised controlled trial of a prognostic assessment and management pathway to reduce the length of hospital stay in normotensive patients with acute pulmonary embolism.

BACKGROUND: The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown. METHODS: We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes. RESULTS: Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7-4.2 days) in the intervention group and 6.1 days (IQR 5.7-6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates. CONCLUSIONS: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation: A Randomized Clinical Trial.

Importance: Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD). Objective: To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation. Design, Setting, and Participants: Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020). Interventions: Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367). Main Outcomes and Measures: The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected. Results: Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, -6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, -2.0% [95% CI, -4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, -3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, -1.7% [95% CI, -5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, -1.9% to 1.8%]; P = .99). Conclusions and Relevance: Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02238639.

Rivaroxaban for extended thromboprophylaxis in acutely ill medical patients 75 years of age or older.

BACKGROUND: Although older patients are at increased risk for venous thromboembolism (VTE), thromboprophylaxis is underused because of bleeding concerns. The MARINER trial evaluated whether rivaroxaban reduced symptomatic postdischarge VTE in acutely ill medical patients. OBJECTIVES: We hypothesized that rivaroxaban would have a favorable benefit/risk profile in patients ≥75 years of age. METHODS: Patients were randomized in a double-blind manner at hospital discharge to rivaroxaban (10 mg/day for creatinine clearance ≥50 ml/min; 7.5 mg/day for ≥30-<50 ml/min) or placebo for 45 days. Using a Cox proportional hazard model including treatment as a covariate, we compared the risk of the primary efficacy outcome (symptomatic VTE plus VTE-related death in the intention-to-treat population) and safety outcome (International Society on Thrombosis and Haemostasis major bleeding in the safety population) in the prespecified subgroups of patients ≥ and <75 years of age. RESULTS: The primary event rate in patients ≥75 years of age was 2-fold higher than that in those <75 years. The incidence of the primary efficacy outcomes in both age groups was numerically lower with rivaroxaban than with placebo (≥75: 1.2% and 1.6%, HR 0.73, 95% CI 0.43-1.22; <75 0.6% and 0.8%, HR 0.78, 95% CI 0.46-1.32; interaction p-value for age group = .85). The incidence of major bleeding was low and similar in the two age and treatment groups (interaction p value for age group = .35). CONCLUSION: Symptomatic VTE and VTE-related death occur frequently in older patients with acute medical illness. The benefit/risk profile of rivaroxaban in patients ≥75 years of age appears consistent with that observed in the general population.

Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis.

BACKGROUND: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations. RESEARCH QUESTION: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD. STUDY DESIGN AND METHODS: Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status. RESULTS: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001. INTERPRETATION: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life: A Secondary Analysis of the Long-Term Oxygen Treatment Trial.

BACKGROUND: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. RESEARCH QUESTION: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? STUDY DESIGN AND METHODS: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. RESULTS: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). INTERPRETATION: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.

Systolic blood pressure and mortality in acute symptomatic pulmonary embolism.

BACKGROUND: The optimal cutoff for systolic blood pressure (SBP) level to define high-risk pulmonary embolism (PE) remains to be defined. METHODS: To evaluate the relationship between SBP levels on admission and mortality in patients with acute symptomatic PE, the current study included 39,257 consecutive patients with acute symptomatic PE from the RIETE registry between 2001 and 2018. Primary outcomes included all-cause and PE-specific 30-day mortality. Secondary outcomes included major bleeding and recurrent venous thromboembolism (VTE). RESULTS: There was a linear inverse relationship between admission SBP and 30-day all-cause and PE-related mortality that persisted after multivariable adjustment. Patients in the lower SBP strata had higher rates of all-cause death (reference: SBP 110-129 mmHg) (adjusted odds ratio [OR] 2.9; 95% confidence interval [CI], 2.0-4.2 for SBP <70 mmHg; and OR 1.7; 95% CI, 1.4-2.1 for SBP 70-89 mmHg). The findings for 30-day PE-related mortality were similar (adjusted OR 4.4; 95% CI, 2.7-7.2 for SBP <70 mmHg; and OR 2.6; 95% CI, 1.9-3.4 for SBP 70-89 mmHg). Patients in the higher strata of SBP had significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR 0.7; 95% CI, 0.5-0.9 for SBP 170-190 mmHg; and OR 0.6; 95% CI, 0.4-0.9 for SBP >190 mmHg). Consistent findings were also observed for 30-day PE-related death. CONCLUSIONS: In patients with acute symptomatic PE, a low SBP portends an increased risk of all-cause and PE-related mortality. The highest mortality was observed in patients with SBP <70 mmHg.

Intermediate-High Risk Pulmonary Embolism.

Limited information exists about the prevalence, management, and outcomes of intermediate-high risk patients with acute pulmonary embolism (PE). In a prospective cohort study, we evaluated consecutive patients with intermediate-high risk PE at a large, tertiary, academic medical center between January 1, 2015 and March 31, 2019. Adjudicated outcomes included PE-related mortality and a complicated course through 30 days after initiation of PE treatment. Repeat systolic blood pressure (SBP), heart rate (HR), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) measurements, and echocardiography were performed within 48 hours after diagnosis. Among 1,015 normotensive patients with acute PE, 97 (9.6%) had intermediate-high risk PE. A 30-day complicated course and 30-day PE-related mortality occurred in 23 (24%) and 7 patients (7.2%) with intermediate-high risk PE. Seventeen (18%) intermediate-high risk patients received reperfusion therapy. Within 48 hours after initiation of anticoagulation, normalization of SBP, HR, cTnI, BNP, and echocardiography occurred in 82, 86, 78, 72, and 33% of survivors with intermediate-high risk PE who did not receive immediate thrombolysis. A complicated course between day 2 and day 30 after PE diagnosis for the patients who normalized SBP, HR, cTnI, BNP, and echocardiography measured at 48 hours occurred in 2.9, 1.4, 4.5, 3.3, and 14.3%, respectively. Intermediate-high risk PE occurs in approximately one-tenth of patients with acute symptomatic PE, and is associated with high morbidity and mortality. Normalization of HR 48 hours after diagnosis might identify a group of patients with a very low risk of deterioration during the first month of follow-up.

Donation after circulatory death in lung transplantation-five-year follow-up from ISHLT Registry.

BACKGROUND: This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD). METHODS: We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model. RESULTS: The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p < 0.001), but donor type was not (DCD-III vs DBD; hazard ratio, 1.04 [0.90-1.19], p = 0.61). CONCLUSION: This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality.

Hospital volume and outcomes for acute pulmonary embolism: multinational population based cohort study.

OBJECTIVES: To evaluate the association between experience in the management of acute pulmonary embolism, reflected by hospital case volume, and mortality. DESIGN: Multinational population based cohort study using data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry between 1 January 2001 and 31 August 2018. SETTING: 353 hospitals in 16 countries. PARTICIPANTS: 39 257 consecutive patients with confirmed diagnosis of acute symptomatic pulmonary embolism. MAIN OUTCOME MEASURE: Pulmonary embolism related mortality within 30 days after diagnosis of the condition. RESULTS: Patients with acute symptomatic pulmonary embolism admitted to high volume hospitals (>40 pulmonary embolisms per year) had a higher burden of comorbidities. A significant inverse association was seen between annual hospital volume and pulmonary embolism related mortality. Admission to hospitals in the highest quarter (that is, >40 pulmonary embolisms per year) was associated with a 44% reduction in the adjusted odds of pulmonary embolism related mortality at 30 days compared with admission to hospitals in the lowest quarter (<15 pulmonary embolisms per year; adjusted risk 1.3% v 2.3%; adjusted odds ratio 0.56 (95% confidence interval 0.33 to 0.95); P=0.03). Results were consistent in all sensitivity analyses. All cause mortality at 30 days was not significantly reduced between the two quarters (adjusted odds ratio 0.78 (0.50 to 1.22); P=0.28). Survivors showed little change in the odds of recurrent venous thromboembolism (odds ratio 0.76 (0.49 to 1.19)) or major bleeding (1.07 (0.77 to 1.47)) between the low and high volume hospitals. CONCLUSIONS: In patients with acute symptomatic pulmonary embolism, admission to high volume hospitals was associated with significant reductions in adjusted pulmonary embolism related mortality at 30 days. These findings could have implications for management strategies.

Comparison of All-Cause Mortality Following VTE Treatment Between Propensity Score-Adjusted Observational Studies and Matched Randomized Controlled Trials: Meta-Epidemiologic Study.

BACKGROUND: It is unknown whether propensity score-adjusted observational studies produce results comparable to those of randomized controlled trials (RCTs) that address similar VTE treatment issues. METHODS: The PubMed and Web of Science databases were systematically searched for propensity score-adjusted observational studies, RCTs, and meta-analyses of RCTs that estimated all-cause mortality following VTE treatment. After identifying distinct clinical treatment issues evaluated in the eligible observational studies, a standardized algorithm was used to identify and match at least one RCT or RCT meta-analysis publication for paired study design analyses. Meta-analyses were used to summarize groups of studies. Treatment efficacy statistics (relative ORs) were compared between the paired observational and RCT studies, and the summary relative ORs for all study design pairs were also calculated. RESULTS: The observational and RCT study pairs assessed seven clinical treatment issues. Overall, the observational study-RCT pairs did not exhibit significantly different mortality estimates (summary relative OR, 0.89; 95% CI, 0.32-1.46; I2 = 23%). However, two of the seven treatment issue study pairs (thrombolysis vs anticoagulation for pulmonary embolism; once- vs twice-daily enoxaparin for VTE) exhibited a significantly different treatment effect direction, and there was a substantial (nonsignificant) difference in the magnitude of the effect in another two of the study pairs (rivaroxaban vs vitamin K antagonists for VTE; home treatment vs hospitalization for DVT). CONCLUSIONS: This systematic comparison across seven VTE treatment topics suggests that propensity score-adjusted observational studies and RCTs often exhibit similar all-cause mortality, although differences in the direction or the magnitude of estimated treatment effects may occasionally occur. TRIAL REGISTRY: PROSPERO; CRD42018087819; URL: http://www.crd.york.ac.uk/PROSPERO.

Association between Allosensitization and Waiting List Outcomes among Adult Lung Transplant Candidates in the United States.

Rationale: Allosensitization may be a barrier to lung transplant. Currently, consideration is not given to allosensitization when assigning priority on the lung transplant waiting list. Objectives: We aimed to examine the association between allosensitization and waiting list outcomes. Methods: We conducted a retrospective single-center cohort study of adults listed for lung transplant at our center between January 1, 2006, and December 31, 2016. We screened candidates for human leukocyte antigen antibodies before listing and examined the association between allosensitization and waiting list outcomes, including likelihood of transplant and death on the waiting list, using a competing risk model. Calculated panel-reactive antibody (CPRA) was used as a continuous measure of allosensitization. Results: Among 746 candidates who were listed for lung transplant during the study period, 263 (35%) were allosensitized, and 483 (65%) were not. In unadjusted analysis, allosensitized candidates had a decreased likelihood of transplant compared with nonallosensitized candidates (subhazard ratio [sHR], 0.71; 95% confidence interval [CI], 0.60-0.83; P < 0.001) and were more likely to die on the waiting list (sHR, 1.66; 95% CI, 1.08-2.58; P < 0.001). In multivariable modeling, increasing CPRA was associated with an increased risk of death and a decreased likelihood of transplant (sHR for death, 1.15 per 10% increase in CPRA; 95% CI, 1.07-1.22; P < 0.001; sHR for transplant, 0.89 per 10% increase in CPRA; 95% CI, 0.86-0.91; P < 0.001). Conclusions: Broad allosensitization was associated with longer waiting times, decreased likelihood of transplant, and increased risk of death among candidates on the waiting list for lung transplant. Consideration of allosensitization in organ allocation strategies might help mitigate this increased risk in highly allosensitized candidates.

Characteristics at the time of oxygen initiation associated with its adherence: Findings from the COPD Long-term Oxygen Treatment Trial.

RATIONALE: Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear. OBJECTIVES: To identify patient characteristics at the time of oxygen initiation associated with its adherence. METHODS: We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial. Participants were prescribed continuous (n = 214) or intermittent (n = 145) oxygen based on desaturation patterns at study entry. At the time of initial prescription, participants rated their perceived readiness, confidence, and importance to use oxygen on a 0-10 scale (0 = not at all, 10 = very much). During follow-up, they self-reported average hours per day of use (adherence). Adherence was averaged over short-term (0-30 days), medium-term (months 9-12), and long-term (month 13 to last follow-up) intervals. Multivariable logistic regression models explored characteristics associated with high adherence (≥16 h/day [continuous] or ≥8 h/day [intermittent]) during each time interval. RESULTS: Participant readiness, confidence, and importance at the time of oxygen initiation were associated with high short- and medium-term adherence. For each unit increase in baseline readiness, the odds of high short-term adherence increased by 21% (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05-1.40) and 94% (OR 1.94, 95% CI 1.45-2.59) in the continuous and intermittent groups, respectively. In both groups, high adherence in the medium-term was associated with high adherence in the long-term (continuous, OR 12.49, 95% CI 4.90-31.79; intermittent, OR 38.08, 95% CI 6.96-208.20). CONCLUSIONS: Readiness, confidence, and importance to use LTOT at initiation, and early high adherence, are significantly associated with long-term oxygen adherence.

Chest computed tomography imaging improves potential lung donor assessment.

OBJECTIVE: Chest computed tomography (CT) imaging is being increasingly used for potential lung donor assessment. However, the efficacy of CT imaging in this setting remains unknown. We hypothesize that chest CT imaging independently affects the decision-making process in donor lung utilization. METHODS: We conducted a retrospective cohort study of all adult donation after brain death donors managed through our local organ procurement organization from June 2011 to November 2016. An experienced thoracic radiologist independently reviewed donor chest CT and chest x-ray images in a blinded, standardized manner to determine the presence of structural lung disease (eg, emphysema, interstitial lung disease [ILD]) and acute abnormalities (eg, traumatic lung injury [TLI]). Distinct models of lung utilization were fit to groups with initial partial pressure of oxygen (iPaO2) ≤300 mm Hg (suboptimal) and iPaO2 >300 mm Hg (optimal). RESULTS: The organ procurement organization managed 753 donors during the study period, with a lung utilization rate ([lung donors/all organ donors] × 100) of 36.5% (275 of 753). Four hundred forty-five (59.1%) donors received chest CT imaging, revealing emphysema (13.7%), ILD (2.5%), and TLI (7.2%). In univariate analysis, findings of TLI (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61) were positively associated with lung utilization, whereas findings of emphysema (OR, 0.18; CI, 0.08-0.40) were negatively associated with utilization. In multivariate analysis, CT findings of emphysema (OR, 0.21; CI 0.08-0.54) remained negatively associated with utilization. No potential donors with CT findings of ILD became lung donors. After controlling for chest x-ray findings, chest CT imaging findings of structural lung disease remained negatively associated with utilization (P = .0001). Lung utilization rate in the suboptimal and optimal iPaO2 populations was 35.1% and 41.4%, respectively, and CT findings of emphysema had a significant association with nonutilization in both groups. CONCLUSIONS: In the evaluation of potential lung donors, chest CT imaging findings of structural lung disease, such as emphysema and ILD, have a significant negative association with lung utilization. Our findings suggest that chest CT imaging might be an important adjunct to conventional lung donor assessment criteria.

Technical Considerations for Lung Transplantation in Kartagener's Syndrome.

Kartagener's syndrome is a rare genetic disorder of ciliated epithelial cells associated with recurrent respiratory tract infections, bronchiectasis, and situs inversus. In some patients, the accumulation of airway secretions and recurrent infections lead to end-stage lung disease, for which lung transplantation is the only effective treatment. Anatomical variations, such as dextrocardia and pulmonary situs inversus, make the procedure challenging, yet feasible with certain technical modifications and careful preparation of donor lungs. We report a case of bilateral lung transplantation without the use of cardiopulmonary bypass in a patient with Kartagener's syndrome while describing important technical details of the operation.

Accuracy and Interobserver Reliability of the Simplified Pulmonary Embolism Severity Index Versus the Hestia Criteria for Patients With Pulmonary Embolism.

OBJECTIVES: The objective was to assess and compare the accuracy and interobserver reliability of the simplified Pulmonary Embolism Severity Index (sPESI) and the Hestia criteria for predicting short-term mortality in patients with pulmonary embolism (PE). METHODS: This prospective cohort study evaluated consecutive eligible adults with PE diagnosed in the emergency department (ED) at a large, tertiary, academic medical center in the era January 1, 2015, to December 30, 2017. We assessed and compared sPESI and Hestia criteria prognostic accuracy for 30-day all-cause mortality after PE diagnosis and their interobserver reliability for classifying patients as low risk or high risk. Two clinician investigators scored both prediction tools during the ED evaluation. We used the kappa statistic to test for agreement. RESULTS: The 488-patient cohort had a mean (±SD) age of 69.0 (±17.1) years and an approximately even sex distribution. The investigators classified one-quarter of patients as low risk using the sPESI and Hestia criteria (28% vs. 27%, respectively). During the 30-day follow-up, 31 of the 488 (6.4%) patients died. Patients classified as low risk according to the sPESI and the Hestia criteria had a similar 30-day mortality (sPESI 0.7% [1/135], 95% confidence interval [CI] = 0.0%-4.0%; Hestia 2.3% [3/132], 95% CI = 0.5%-6.5%). The two observers had good agreement (κ = 0.80) for the Hestia criteria and very good agreement (κ = 0.97) for the sPESI. CONCLUSION: The sPESI and the Hestia criteria had similar risk classification determination and prognostic accuracy for 30-day mortality after PE. However, the succinct and more objective sPESI had higher interobserver reliability than the Hestia criteria.