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McConnell's sign predicts normotensive shock in patients with acute pulmonary embolism [Letter]

Zhang, Robert S; Rhee, Aaron J; Yuriditsky, Eugene; Nayar, Ambika C; Elbaum, Lindsay S; Horowitz, James M; Greco, Allison A; Postelnicu, Radu; Alviar, Carlos L; Bangalore, Sripal
BACKGROUND:Patients with intermediate-risk pulmonary embolism (PE) and normotensive shock may have worse outcomes. However, diagnosis of normotensive shock requires invasive hemodynamics. Our objective was to assess the predictive value of McConnell's sign in identifying normotensive shock in patients with intermediate-risk PE. METHODS:and clinical evidence of hypoperfusion (i.e. elevated lactate, oliguria). The primary outcome was the association between McConnell's sign and normotensive shock. RESULTS:, p = 0.003), and higher rates of normotensive shock (76 % vs 27 %, p = 0.005). McConnell's sign had a sensitivity of 88 % and specificity of 53 % for identifying intermediate-risk PE patients with normotensive shock. Patients with McConnell's sign had an increased odds (odds ratio 8.38, confidence interval: 1.73-40.53, p = 0.008; area under the curve 0.70, 95 % confidence interval: 0.56-0.85) of normotensive shock. CONCLUSION/CONCLUSIONS:This is the first study to suggest that McConnell's sign may identify those in the intermediate-risk group who are at risk for normotensive shock. Larger cohorts are needed to validate our findings.
PMID: 38906415
ISSN: 1876-4738
CID: 5672452

Catheter-based therapy for high-risk or intermediate-risk pulmonary embolism: death and re-hospitalization

Leiva, Orly; Alviar, Carlos; Khandhar, Sameer; Parikh, Sahil A; Toma, Catalin; Postelnicu, Radu; Horowitz, James; Mukherjee, Vikramjit; Greco, Allison; Bangalore, Sripal
BACKGROUND AND AIMS/OBJECTIVE:Catheter-based therapies (CBTs) have been developed as a treatment option in patients with pulmonary embolism (PE). There remains a paucity of data to inform decision-making in patients with intermediate-risk or high-risk PE. The aim of this study was to characterize in-hospital and readmission outcomes in patients with intermediate-risk or high-risk PE treated with vs. without CBT in a large retrospective registry. METHODS:Patients hospitalized with intermediate-risk or high-risk PE were identified using the 2017-20 National Readmission Database. In-hospital outcomes included death and bleeding and 30- and 90-day readmission outcomes including all-cause, venous thromboembolism (VTE)-related and bleeding-related readmissions. Inverse probability of treatment weighting (IPTW) was utilized to compare outcomes between CBT and no CBT. RESULTS:A total of 14 903 [2076 (13.9%) with CBT] and 42 829 [8824 (20.6%) with CBT] patients with high-risk and intermediate-risk PE were included, respectively. Prior to IPTW, patients with CBT were younger and less likely to have cancer and cardiac arrest, receive systemic thrombolysis, or be on mechanical ventilation. In the IPTW logistic regression model, CBT was associated with lower odds of in-hospital death in high-risk [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.80-0.87] and intermediate-risk PE (OR 0.76, 95% CI 0.70-0.83). Patients with high-risk PE treated with CBT were associated with lower risk of 90-day all-cause [hazard ratio (HR) 0.77, 95% CI 0.71-0.83] and VTE (HR 0.46, 95% CI 0.34-0.63) readmission. Patients with intermediate-risk PE treated with CBT were associated with lower risk of 90-day all-cause (HR 0.75, 95% CI 0.72-0.79) and VTE (HR 0.66, 95% CI 0.57-0.76) readmission. CONCLUSIONS:Among patients with high-risk or intermediate-risk PE, CBT was associated with lower in-hospital death and 90-day readmission. Prospective, randomized trials are needed to confirm these findings.
PMID: 38573048
ISSN: 1522-9645
CID: 5664662

Low left ventricular outflow tract velocity time integral predicts normotensive shock in patients with acute pulmonary embolism [Letter]

Zhang, Robert S; Yuriditsky, Eugene; Nayar, Ambika C; Elbaum, Lindsay; Greco, Allison A; Rhee, Aaron J; Mukherjee, Vikramjit; Keller, Norma; Alviar, Carlos L; Horowitz, James M; Bangalore, Sripal
In this study, we found that a low LVOT VTI (<15 cm), a simple bedside point-of-care measurement, predicts normotensive shock in patients with acute intermediate-risk PE.
PMID: 38670834
ISSN: 1097-6744
CID: 5657872

Catheter-based therapy for intermediate or high-risk pulmonary embolism is associated with lower in-hospital mortality in patients with cancer: Insights from the National Inpatient Sample

Leiva, Orly; Yuriditsky, Eugene; Postelnicu, Radu; Yang, Eric H; Mukherjee, Vikramjit; Greco, Allison; Horowitz, James; Alviar, Carlos; Bangalore, Sripal
BACKGROUND:Pulmonary embolism (PE) is a common complication among patients with cancer and is a significant contributor to morbidity and mortality. Catheter-based therapies (CBT), including catheter-directed thrombolysis (CDT) and mechanical thrombectomy, have been developed and are used in patients with intermediate or high-risk PE. However, there is a paucity of data on outcomes in patients with cancer as most clinical studies exclude this group of patients. AIMS/OBJECTIVE:To characterize outcomes of patients with cancer admitted with intermediate or high-risk PE treated with CBT compared with no CBT. METHODS:Patients with an admission diagnosis of intermediate or high-risk PE and a history of cancer from October 2015 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest were in-hospital death or cardiac arrest (CA) and major bleeding. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes between patients treated with and without CBT. Variables that remained unbalanced after IPTW were adjusted using multivariable logistic regression. RESULTS:A total of 2084 unweighted admissions (10,420 weighted) for intermediate or high-risk PE and cancer were included, of which 136 (6.5%) were treated with CBT. After IPTW, CBT was associated with lower death or CA (aOR 0.54, 95% CI 0.46-0.64) but higher major bleeding (aOR 1.41, 95% CI 1.21-1.65). After stratifying by PE risk type, patients treated with CBT had lower risk of death or CA in both intermediate (aOR 0.52, 95% CI 0.36-0.75) and high-risk PE (aOR 0.48, 95% CI 0.33-0.53). However, patients with CBT were associated with increased risk of major bleeding in intermediate-risk PE (aOR 2.12, 95% CI 1.67-2.69) but not in those with high-risk PE (aOR 0.84, 95% CI 0.66-1.07). CONCLUSIONS:Among patients with cancer hospitalized with intermediate or high-risk PE, treatment with CBT was associated with lower risk of in-hospital death or CA but higher risk of bleeding. Prospective studies and inclusion of patients with cancer in randomized trials are warranted to confirm our findings.
PMID: 37997287
ISSN: 1522-726x
CID: 5608872

Quality and rapidity of anticoagulation in patients with acute pulmonary embolism undergoing mechanical thrombectomy

Zhang, Robert S; Ho, Alvin M; Elbaum, Lindsay; Greco, Allison A; Hall, Sylvie; Postelnicu, Radu; Mukherjee, Vikramjit; Maqsood, Muhammad H; Keller, Norma; Alviar, Carlos L; Bangalore, Sripal
The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE.
PMID: 38071002
ISSN: 1097-6744
CID: 5589832

Validating the Composite Pulmonary Embolism Shock Score for Predicting Normotensive Shock in Intermediate-Risk Pulmonary Embolism

Zhang, Robert S; Alam, Usman; Sharp, Andrew S P; Giri, Jay S; Greco, Allison A; Secemsky, Eric A; Postelnicu, Radu; Sethi, Sanjum S; Alviar, Carlos L; Bangalore, Sripal
PMID: 38063026
ISSN: 1941-7632
CID: 5591522

Efficacy and Safety of Anticoagulation, Catheter-Directed Thrombolysis, or Systemic Thrombolysis in Acute Pulmonary Embolism

Zhang, Robert S; Maqsood, Muhammad H; Sharp, Andrew S P; Postelnicu, Radu; Sethi, Sanjum S; Greco, Allison; Alviar, Carlos; Bangalore, Sripal
BACKGROUND:The optimal treatment strategy of patients with pulmonary embolism (PE) (especially those with intermediate risk) continues to evolve and remains controversial. OBJECTIVES/OBJECTIVE:This study sought to compare the efficacy and safety of anticoagulation (AC) alone, catheter-directed thrombolysis (CDT), and systemic thrombolysis (ST) in patients with acute PE. METHODS:PubMed and EMBASE were searched for randomized controlled trials or observational studies which compared outcomes of AC alone, CDT, and ST in acute PE. Efficacy outcome was all-cause mortality. Safety outcomes were major bleeding and intracranial hemorrhage (ICH). RESULTS:We identified 45 studies (17 randomized controlled trials, 2 prospective nonrandomized trials, and 26 retrospective observational trials), which included 81,705 patients. When compared with AC alone, CDT had lower mortality (OR: 0.55; 95% CI: 0.39-0.80) but higher major bleeding (OR: 1.84; 95% CI: 1.10-3.08) and numerically higher ICH (OR: 1.51; 95% CI: 0.75-3.04). ST was associated with no difference in mortality but higher major bleeding (OR: 2.16; 95% CI: 1.38-3.38) and ICH (OR: 2.26; 95% CI: 1.14-4.48) when compared with AC alone. The risk of mortality (OR: 2.05; 95% CI: 1.46-2.89) and ICH (OR: 1.50; 95% CI: 1.13-1.99) was higher with ST when compared with CDT. Findings were similar when analysis was restricted to trials of intermediate risk PE. CONCLUSIONS:In patients with acute PE, when compared with AC alone, CDT was associated with a lower mortality but higher risk of bleeding. Moreover, CDT had an enhanced safety profile when compared with ST.
PMID: 37855802
ISSN: 1876-7605
CID: 5609702

Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk

Brosnahan, Shari B; Chen, Xian Jie Cindy; Chung, Juri; Altshuler, Diana; Islam, Shahidul; Thomas, Sarun V; Winner, Megan D; Greco, Allison A; Divers, Jasmin; Spiegler, Peter; Sterman, Daniel H; Parnia, Sam
BACKGROUND:Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES/OBJECTIVE:The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS:A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS:= 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE/UNASSIGNED:Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.
PMID: 34180274
ISSN: 1542-6270
CID: 4926192

Physician failure to stratify patients hospitalized with acute pulmonary embolism

Jacobs, Mitchell D; Greco, Allison; Mukhtar, Umer; Dunn, Jonathan; Scharf, Michael L
OBJECTIVES/OBJECTIVE:In 2011, the AHA recommended risk stratification of patients with acute pulmonary embolism (PE). Failure to risk stratify may cause under recognition of intermediate-risk PE and its attendant short- and long-term consequences. We sought to determine if patients hospitalized with acute PE were appropriately risk stratified according to the 2011 AHA Scientific Statement within our hospital system and whether differences exist in adherence to risk stratification by hospital or treating hospital service. We also wished to know the frequency of in-hospital consultations for acute PE which might assist in the risk stratification process. METHODS:This is a retrospective chart audit of all patients hospitalized with a diagnosis of acute PE between January 2011 and December 2013 at our 937-bed metropolitan, three hospital system comprised of academic University, neuroscience Specialty, and teaching Community hospitals. We evaluated the presence of imaging, laboratory tests, and specialty consultation within 72 h of PE diagnosis by hospital. RESULTS:701 patients with acute PE were admitted to our hospital system during the study period. 308 patients (43.9%) met criteria for intermediate-risk PE. 347 patients (49.5%) were considered 'Low-Risk - At Risk', patients defined in a low-risk category not having undergone all recommended risk stratification testing and so truly may have been in a higher risk category. No specialty consultations were utilized for 265 patients (37.8%). CONCLUSIONS:Our large metropolitan hospital system inadequately risk stratifies hospitalized patients with acute PE. Because nearly one-half of patients with acute PE did not have all recommended testing, clinicians may be under recognizing patients with intermediate-risk PE and their risk for long-term morbidity. Specialty consultations were underutilized and may help guide medical decision-making.
PMID: 28835184
ISSN: 2154-8331
CID: 4494102

Differential effects of hypoxic and hyperoxic stress-induced hypertrophy in cultured chick fetal cardiac myocytes

Greco, Allison A; Gomez, George
The adult heart responds to contraction demands by hypertrophy, or enlargement, of cardiac myocytes. Adaptive hypertrophy can occur in response to hyperoxic conditions such as exercise, while pathological factors that result in hypoxia ultimately result in heart failure. The difference in the outcomes produced by pathologically versus physiologically induced hypertrophy suggests that the cellular signaling pathways or conditions of myocytes may be different at the cellular level. The structural and functional changes in myocytes resulting from hyperoxia (simulated using hydrogen peroxide) and hypoxia (using oxygen deprivation) were tested on fetal chick cardiac myocytes grown in vitro. Structural changes were measured using immunostaining for α-sarcomeric actin or MyoD, while functional changes were assessed using immunostaining for calcium/calmodulin-dependent kinase (CaMKII) and by measuring intracellular calcium fluxes using live cell fluorescence imaging. Both hypoxic and hyperoxic stress resulted in an upregulation of actin and MyoD expression. Similarly, voltage-gated channels governing myocyte depolarization and the regulation of CaMK were unchanged by hyperoxic or hypoxic conditions. However, the dynamic features of calcium fluxes elicited by caffeine or epinephrine were different in cells subjected to hypoxia versus hyperoxia, suggesting that these different conditions differentially affect components of ligand-activated signaling pathways that regulate calcium. Our results suggest that changes in signaling pathways, rather than structural organization, may mediate the different outcomes associated with hyperoxia-induced versus hypoxia-induced hypertrophy, and these changes are likely initiated at the cellular level.
PMID: 23990386
ISSN: 1543-706x
CID: 4494092