RESUMEN
Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1-3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6-14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.
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Autopsia , Encéfalo , COVID-19 , Especificidad de Órganos , SARS-CoV-2 , Humanos , Encéfalo/virología , COVID-19/virología , ARN Viral/análisis , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/patogenicidad , SARS-CoV-2/fisiología , Replicación Viral , Factores de Tiempo , Sistema Respiratorio/patología , Sistema Respiratorio/virologíaRESUMEN
Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR-positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.
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COVID-19 , Humanos , SARS-CoV-2 , Autopsia , ARN Viral/análisis , InflamaciónRESUMEN
Sickle cell disease (SCD) is associated with substantial morbidity and early mortality in afflicted adults. Cardiopulmonary complications that occur at increased frequency in SCD such as pulmonary embolism, pulmonary arterial hypertension, and acute chest syndrome can acutely worsen right ventricular function and lead to cardiogenic shock. Mechanical circulatory support including venoarterial extracorporeal membrane oxygenation (VA ECMO) is being increasingly utilized to treat hemodynamic collapse in various patient populations. However, a paucity of literature exists to guide the use of mechanical circulatory support in adults with SCD where disease-related sequela and unique hematologic aspects of this disorder may complicate extracorporeal therapy and must be understood. Here, we review the literature and describe three cases of adult patients with SCD who developed cardiogenic shock from acute decompensated right heart failure and were treated clinically with VA ECMO. Using an in vitro ECMO system, we investigate a potential increased risk of systemic fat emboli in patients with SCD who may be experiencing vaso-occlusive events with bone marrow involvement given the high-volume shunting of blood from venous to arterial systems with VA ECMO. The purpose of this study is to describe available extracorporeal life support experiences, review potential complications, and discuss the special considerations needed to further our understanding of the utility of VA ECMO in those with SCD.
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Although the risk of SARS-CoV-2 transmission through lung transplantation from acutely infected donors is high, the risks of virus transmission and long-term lung allograft outcomes are not as well described when using pulmonary organs from COVID-19-recovered donors. We describe successful lung transplantation for a COVID-19-related lung injury using lungs from a COVID-19-recovered donor who was retrospectively found to have detectable genomic SARS-CoV-2 RNA in the lung tissue by multiple highly sensitive assays. However, SARS-CoV-2 subgenomic RNA (sgRNA), a marker of viral replication, was not detectable in the donor respiratory tissues. One year after lung transplantation, the recipient has a good functional status, walking 1 mile several times per week without the need for supplemental oxygen and without any evidence of donor-derived SARS-CoV-2 transmission. Our findings highlight the limitations of current clinical laboratory diagnostic assays in detecting the persistence of SARS-CoV-2 RNA in the lung tissue. The persistence of SARS-CoV-2 RNA in the donor tissue did not appear to represent active viral replication via sgRNA testing and, most importantly, did not negatively impact the allograft outcome in the first year after lung transplantation. sgRNA is easily performed and may be a useful assay for assessing viral infectivity in organs from donors with a recent infection.
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COVID-19 , Trasplante de Pulmón , Humanos , SARS-CoV-2/genética , ARN Subgenómico , ARN Viral/genética , Estudios Retrospectivos , AloinjertosRESUMEN
BACKGROUND: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS. METHODS: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome. RESULTS: This study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization. CONCLUSIONS: There were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Estudios Retrospectivos , COVID-19/terapia , Sobrevivientes/psicologíaRESUMEN
INTRODUCTION: It remains unclear whether patients who will not accept allogeneic blood transfusion can be managed successfully with veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO). The objective of our study was to determine what percentage of V-A ECMO patients were managed without allogeneic blood transfusion. METHODS: This was a retrospective, observational cohort study of patients with cardiogenic shock requiring V-A ECMO between January 2016 and January 2019. The primary outcome was avoidance of any allogeneic blood transfusion. RESULTS: Of the 206 patients included, 23 (11.2%) were managed without any allogeneic blood transfusion. Fourteen (60.9%) avoided allogeneic blood transfusion during their entire hospitalization. "No-transfusion" patients were younger, more commonly men, were less likely to have a prior diagnosis of hypertension or coronary artery disease, had higher baseline hemoglobin, had higher SAVE scores, and were less likely to have received aspirin before ECMO. No patients in the "no-transfusion" group had major bleeding compared to 35% of patients in the blood transfusion group (p < 0.001). In-hospital mortality was 17.4% for those who avoided blood transfusion and 41.5% for those who received blood transfusion (p = 0.04). ECMO duration was significantly shorter in patients who avoided blood transfusion compared to those who received blood transfusion (median 3.5 vs 7 days, p < 0.001). CONCLUSIONS: Select patients can be successfully managed on V-A ECMO without allogeneic blood transfusion. Jehovah's Witnesses and other patients with objections to allogeneic transfusion might be offered V-A ECMO if its anticipated duration is short (e.g. <7 days) and baseline hemoglobin concentration is high (e.g. ≥10 mg/dL).
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Oxigenación por Membrana Extracorpórea , Trasplante de Células Madre Hematopoyéticas , Masculino , Humanos , Estudios de Cohortes , Choque Cardiogénico , Estudios Retrospectivos , Transfusión Sanguínea , HemoglobinasRESUMEN
INTRODUCTION: The PREdiction of Survival on ECMO Therapy Score (PRESET-Score) predicts mortality while on veno-venous extracorporeal membrane oxygenation (VV ECMO) for acute respiratory distress syndrome. The aim of our study was to assess the association between PRESET-Score and survival in a large COVID-19 VV ECMO cohort. METHODS: This was a single-center retrospective study of COVID-19 VV ECMO patients from 15 March 2020, to 30 November 2021. Univariable and Multivariable analyses were performed to assess patient survival and score differences. RESULTS: A total of 105 patients were included in our analysis with a mean PRESET-Score of 6.74. Overall survival was 65.71%. The mean PRESET-Score was significantly lower in the survivor group (6.03 vs 8.11, p < 0.001). Patients with a PRESET-Score less than or equal to six had improved survival compared to those with a PRESET-Score greater than or equal to 8 (97.7% vs. 32.5%, p < 0.001). In a multivariable logistic regression, a lower PRESET-Score was also predictive of survival (OR 2.84, 95% CI 1.75, 4.63, p < 0.001). CONCLUSION: We demonstrate that lower PRESET scores are associated with improved survival. The utilization of this validated, quantifiable, and objective scoring system to help identify COVID-19 patients with the greatest potential to benefit from VV-ECMO appears feasible. The incorporation of the PRESET-Score into institutional ECMO candidacy guidelines can help insure and improve access of this limited healthcare resource to all critically ill patients.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Humanos , Estudios Retrospectivos , COVID-19/terapia , Síndrome de Dificultad Respiratoria/terapia , Modelos LogísticosRESUMEN
BACKGROUND: Coagulopathic bleeding is common during adult extracorporeal membrane oxygenation (ECMO), and acquired von Willebrand syndrome is a contributing factor. We compared ECMO patient blood samples that were treated in vitro with recombinant von Willebrand Factor concentrate and plasma-derived von Willebrand Factor concentrate. Our hypothesis was that recombinant von Willebrand Factor (vWF) would have greater efficacy in increasing vWF function. Secondarily, we hypothesized that recombinant vWF would have less impact on thrombin generation. METHODS: Thirty ECMO patients and 10 cardiac surgical controls were enrolled in the study. ECMO patient blood samples were treated in vitro with low- and high-dose recombinant vWFs and low- and high-dose plasma-derived vWFs. Whole blood ristocetin-induced platelet aggregation (RIPA), plasma ristocetin cofactor activity (RCo), and thrombin generation were compared between ECMO patient blood samples and control blood samples and between vWF-treated ECMO patient blood samples and nontreated samples. RESULTS: ECMO patient blood samples had severely reduced median RIPA compared to control samples 2 ohms (1-12 [25th-75th percentile]) vs 20 ohms (11-42) (P < .001). Treatment of ECMO patient blood samples with high-dose recombinant vWF significantly increased median RIPA to 10 ohms (2-15) (P < .001), while low-dose recombinant vWF and low- and high-dose plasma-derived vWFs did not significantly increase RIPA; 6 ohms (3-14), 4 ohms (1-13), and 6 ohms (2-10), respectively (P = .25, >.99, and >.99). Treatment with high-dose recombinant vWF and low- and high-dose plasma-derived vWFs significantly increased median plasma RCo to 4.7 international units (IU)/mL (3.7-5.9), 3.3 IU/mL (2.7-4.8), and 3.9 IU/mL (3.4-5.3), respectively, compared to controls 1.8 IU/mL (1.5-2.3) (all P < .001). Treatment with low- and high-dose plasma-derived vWFs significantly increased mean endogenous thrombin potential (6270.2 ± 2038.7 and 6313.1 ± 1913.3) compared to nontreated samples (5856.7 ± 1924.6) (P = .04 and .006), whereas treatment with low- and high-dose recombinant vWFs had no significant effect on mean endogenous thrombin potential (5776.1 ± 2087.3 and 5856.2 ± 1946.4) (P > .99 for both comparisons). CONCLUSIONS: In vitro treatment of ECMO patient blood samples with high-dose recombinant vWF was superior to low-dose recombinant vWF and plasma-derived vWF in terms of improving RIPA. In addition, recombinant vWF treatment did not increase endogenous thrombin potential, which may reduce overall thrombotic risk if it used to treat acquired von Willebrand syndrome in ECMO patients.
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Oxigenación por Membrana Extracorpórea/métodos , Factor VIII/administración & dosificación , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/terapia , Factor de von Willebrand/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Factor VIII/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Plasma , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/sangre , Resultado del Tratamiento , Factor de von Willebrand/metabolismoRESUMEN
Therapeutic plasma exchange (TPE) has a number of applications in cardiac surgical patients and has been used increasingly in high-risk heart and lung transplant patients. In this narrative review, the authors describe TPE principles, complications, and specific indications for TPE, including thrombotic thrombocytopenic purpura, heparin-induced thrombocytopenia, induction of immunotolerance in heart and lung transplant patients, and treatment of antibody-mediated rejection in heart and lung transplant patients. The review is based on published literature and the authors' institutional experience with perioperative TPE in cardiac surgical patients.
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Procedimientos Quirúrgicos Cardíacos , Púrpura Trombocitopénica Trombótica , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Humanos , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/terapiaRESUMEN
The ability of current renal replacement therapy modalities to achieve rapid solute removal is limited by membrane surface area and blood flow rate. Extracorporeal membrane oxygenation offers high blood flow and hemodynamic support that may be harnessed to overcome limitations in traditional renal replacement therapy. Using an extracorporeal membrane oxygenation circuit, we describe a high blood flow, high-efficiency hemofiltration technique using in-line hemofilters (hemoconcentrators) and standard replacement fluid to enhance solute clearance. Using this approach and a total of 5 L of replacement volume per treatment, creatinine (Cr) clearances of 8.3 L/hour and 11.2 L/hour using one and two hemoconcentrators, respectively, were achieved. With use of a high blood flow rate of up to 5 L/min, this hemofiltration technique can potentially offer clearance of 30 times that of continuous renal replacement therapy and of 6 times that of hemodialysis which may expand the ability to remove substances traditionally not considered removable via existing extracorporeal therapies.
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Oxigenación por Membrana Extracorpórea/métodos , Hemofiltración/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Blunt thoracic aortic injury (BTAI) in a patient with an aberrant right subclavian artery (ARSA) presents unique challenges for patient management and aortic repair. Specific considerations include the need to treat coincidental ARSA, subclavian revascularization, and ARSA exclusion. Despite the rise of endovascular repair as the primary modality for aortic repair for BTAI, reports of this technique in the setting of ARSA are limited. Here we describe 3 patients with ARSA who underwent TEVAR for BTAI, and discuss critical management and technical issues in these patients.
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Accidentes de Tránsito , Aneurisma/complicaciones , Aorta Torácica/cirugía , Implantación de Prótesis Vascular , Anomalías Cardiovasculares/complicaciones , Procedimientos Endovasculares , Arteria Subclavia/anomalías , Traumatismos Torácicos/cirugía , Lesiones del Sistema Vascular/cirugía , Heridas no Penetrantes/cirugía , Adulto , Aneurisma/diagnóstico por imagen , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/lesiones , Aortografía/métodos , Prótesis Vascular , Implantación de Prótesis Vascular/instrumentación , Anomalías Cardiovasculares/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Arteria Subclavia/diagnóstico por imagen , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/etiología , Resultado del Tratamiento , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/etiología , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/etiologíaRESUMEN
Human diffuse large B-cell lymphomas (DLBCLs) often aberrantly express oncogenes that generally contain complex secondary structures in their 5' untranslated region (UTR). Oncogenes with complex 5'UTRs require enhanced eIF4A RNA helicase activity for translation. PDCD4 inhibits eIF4A, and PDCD4 knockout mice have a high penetrance for B-cell lymphomas. Here, we show that on B-cell receptor (BCR)-mediated p70s6K activation, PDCD4 is degraded, and eIF4A activity is greatly enhanced. We identified a subset of genes involved in BCR signaling, including CARD11, BCL10, and MALT1, that have complex 5'UTRs and encode proteins with short half-lives. Expression of these known oncogenic proteins is enhanced on BCR activation and is attenuated by the eIF4A inhibitor Silvestrol. Antigen-experienced immunoglobulin (Ig)G(+) splenic B cells, from which most DLBCLs are derived, have higher levels of eIF4A cap-binding activity and protein translation than IgM(+) B cells. Our results suggest that eIF4A-mediated enhancement of oncogene translation may be a critical component for lymphoma progression, and specific targeting of eIF4A may be an attractive therapeutic approach in the management of human B-cell lymphomas.
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Proteínas Adaptadoras de Señalización CARD/metabolismo , ARN Helicasas DEAD-box/metabolismo , Factor 4A Eucariótico de Iniciación/metabolismo , Guanilato Ciclasa/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Regiones no Traducidas 5'/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína 10 de la LLC-Linfoma de Células B , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Western Blotting , Proteínas Adaptadoras de Señalización CARD/genética , Caspasas/genética , Caspasas/metabolismo , Línea Celular Tumoral , Células Cultivadas , ARN Helicasas DEAD-box/antagonistas & inhibidores , ARN Helicasas DEAD-box/genética , Factor 4A Eucariótico de Iniciación/antagonistas & inhibidores , Factor 4A Eucariótico de Iniciación/genética , Guanilato Ciclasa/genética , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Biosíntesis de Proteínas/efectos de los fármacos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Triterpenos/farmacologíaRESUMEN
Developments in diagnosis and treatment have transformed the management of blunt thoracic aortic injuries (BTAIs). For patients in stable condition, treatment practice has shifted from early open repair to nonoperative management for low-grade lesions and routine delayed endovascular repair for more significant injuries. However, effective therapy depends on accurate staging of injury grade and stability to select patients for appropriate management. Recent developments in BTAI risk stratification enable lesion-specific management tailored to the patient and aortic lesion. This review summarizes advances in lesion assessment and treatment and proposes an integrated scheme for the modern management of BTAI.
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Aorta Torácica/cirugía , Traumatismos Torácicos/terapia , Lesiones del Sistema Vascular/terapia , Heridas no Penetrantes/terapia , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/lesiones , Técnicas de Apoyo para la Decisión , Árboles de Decisión , Humanos , Puntaje de Gravedad del Traumatismo , Selección de Paciente , Medición de Riesgo , Factores de Riesgo , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/cirugía , Resultado del Tratamiento , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/cirugía , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/cirugíaRESUMEN
BACKGROUND: Current blunt thoracic aortic injury (BTAI) guidelines recommend early repair of traumatic pseudoaneurysms (PSAs) due to risk for subsequent aortic rupture. Recent analyses indicate that early repair is required only in the setting of high-risk features, while delayed repair is safe and associated with lower morbidity and mortality in appropriately selected patients. To evaluate the appropriate indications for nonoperative management (NOM) of traumatic PSAs, we performed a systematic review of studies reporting outcomes for this management strategy. We hypothesized that NOM is safe in appropriately selected patients with traumatic aortic PSAs. METHODS: English language single- and multi-institutional series reporting NOM of traumatic thoracic aortic PSAs were identified by systematic literature search and review. A descriptive analysis was performed of NOM, with stratification by lesion size and patient follow-up. The primary outcomes were late aortic intervention, aortic-related death, and all-cause mortality. RESULTS: Eighteen studies, which included 937 patients with traumatic PSAs, were analyzed. One hundred ninety-one patients were managed nonoperatively. The primary indication for NOM was prohibitive risk for aortic repair due to severe comorbidities or concurrent injuries. Where reported, PSAs with <50% circumferential involvement accounted for 88% of lesions selected for NOM. Late interventions were required in 4% of patients. Inpatient aortic-related mortality was 2%, and all-cause inpatient mortality was 32%. Although survival at up to 4-7 years was reported, postdischarge follow-up after PSA NOM was limited to <1 year in most studies. CONCLUSIONS: NOM of traumatic aortic PSAs is a common practice in BTAI series reporting lesion-specific management, and is associated with low rates of treatment failure. These findings suggest that routine early repair may not be required for traumatic PSAs, particularly for lesions limited to <50% of the aortic circumference. Definitive repair can be delayed until patient stability and repair timing can be guided by assessment of lesion stability on follow-up imaging.
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Aneurisma Falso/terapia , Aorta Torácica/lesiones , Aneurisma de la Aorta/terapia , Lesiones del Sistema Vascular/terapia , Heridas no Penetrantes/terapia , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/mortalidad , Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/mortalidad , Aortografía/métodos , Comorbilidad , Angiografía por Tomografía Computarizada , Humanos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/mortalidad , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/mortalidadRESUMEN
OBJECTIVE: To evaluate racial differences in the burden of aortic dissection. DESIGN: Retrospective analysis of a comprehensive state-wide inpatient database. SETTING: Acute care hospitals in the state of Maryland, 2009 - 2014. PARTICIPANTS: All hospitalized adults with aortic dissection (AD), stratified by race. MAIN OUTCOME MEASURES: Statewide and county-level population adjusted hospitalization rates, access to specialty aortic care, and mortality. RESULTS: Of 3,719,412 admissions to Maryland hospitals during the study period, 3,190 had AD (.09%; 1665 White, 1525 non-White). Non-White race was more common in patients with AD than without (48% vs. 41%, P<.0001). Adjusted for statewide demographics, admission for AD was 1.4 times more common among non-Whites (11 vs. 8 per 100,000, P<.0001). Non-White race was an independent risk factor for AD admission (OR 1.5, 95% CI 1.4 - 1.7). Among patients with AD, non-Whites were younger and more often female, but had similar or lower rates of cardiovascular comorbidities. Non-White race was not associated with decreased access to care or increased mortality. CONCLUSION: Hospitalization for AD is more common among non-Whites, who develop AD at younger ages despite fewer comorbidities. While clinical correlates are limited from this dataset, this may reflect more severe pathophysiology related to clinical or socioeconomic factors among non-Whites. Further study is warranted to better define this disparity and identify high-risk subgroups who may benefit from aggressive primary prevention.
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Disección Aórtica/etnología , Hospitalización/estadística & datos numéricos , Grupos Raciales , Adulto , Edad de Inicio , Anciano , Comorbilidad , Femenino , Humanos , Masculino , Maryland , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores SocioeconómicosRESUMEN
OBJECTIVE: The optimal timing for repair of a high-grade blunt thoracic aortic injury (BTAI) is uncertain. Delayed repair is common and associated with improved outcomes, but some lesions may rupture during observation. To determine optimal patient selection for appropriate management, we developed a pilot clinical risk score to evaluate aortic stability and predict rupture. METHODS: Patients presenting in stable condition with Society for Vascular Surgery grade III or IV BTAI diagnosed on computed tomography (CT) were retrospectively reviewed. To determine clinical and radiographic factors associated with aortic rupture, patients progressing to aortic rupture (defined by contrast extravasation on CT or on operative or autopsy findings) were compared with those who had no intervention ≤48 hours of admission. A model targeting 100% sensitivity for rupture was generated and internally validated by bootstrap analysis. Clinical utility was tested by comparison with clinical assessment by surgeons experienced in BTAI management who were provided with CT images and clinical data but were blinded to outcome. RESULTS: The derivation cohort included 18 patients whose aorta ruptured and 31 with stable BTAI. There was no difference in age, gender, injury mechanism, nonchest injury severity, blood pressure, or Glasgow Coma Scale on admission between patient groups. As dichotomous factors, admission lactate >4 mM, posterior mediastinal hematoma >10 mm, and lesion/normal aortic diameter ratio >1.4 on the admission CT were independently associated with aortic rupture. The model had an area under the receiver operator curve of .97, and in the presence of any two factors, was 100% sensitive and 84% specific for predicting aortic rupture. No aortic lesions ruptured in patients with fewer than two factors. In contrast, clinical assessment had lower accuracy (65% vs 90% total accuracy, P < .01). CONCLUSIONS: This novel risk score can be applied on admission using clinically relevant factors that incorporate patient physiology, size of the aortic lesion, and extent of the mediastinal hematoma. The model reliably identifies and distinguishes patients with high-grade BTAI who are at risk for early rupture from those with stable lesions. Although preliminary, because it is more accurate than clinical assessment alone, the score may improve patient selection for emergency or delayed intervention.
Asunto(s)
Aorta Torácica/lesiones , Rotura de la Aorta/etiología , Técnicas de Apoyo para la Decisión , Traumatismos Torácicos/diagnóstico , Lesiones del Sistema Vascular/diagnóstico , Heridas no Penetrantes/diagnóstico , Adulto , Anciano , Aorta Torácica/diagnóstico por imagen , Rotura de la Aorta/diagnóstico , Rotura de la Aorta/prevención & control , Aortografía/métodos , Área Bajo la Curva , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Hematoma/etiología , Humanos , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Traumatismos Torácicos/sangre , Traumatismos Torácicos/complicaciones , Traumatismos Torácicos/terapia , Factores de Tiempo , Tomografía Computarizada por Rayos X , Lesiones del Sistema Vascular/sangre , Lesiones del Sistema Vascular/complicaciones , Lesiones del Sistema Vascular/terapia , Heridas no Penetrantes/sangre , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/terapiaRESUMEN
BACKGROUND: Overfeeding and underfeeding are associated with negative outcomes during critical illness. The purpose of this retrospective study was to assess the association between nutrition intake and outcomes for patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO). METHODS: Adults who received VV ECMO August 2017 to June 2020 were screened. Patients with <3 ECMO nutrition support days were excluded. Age, sex, height, weight, ideal body weight (IBW), body mass index, sequential organ failure assessment score, respiratory ECMO survival prediction score, energy, and protein goals were collected. All nutrition intake was collected for the first 14 days of ECMO or until death, decannulation, or oral diet initiation. Outcomes analyzed included mortality and VV ECMO duration. The relationship between nutrition delivery and outcomes was tested with multivariate analysis. Univariate analyses were conducted on obese and nonobese subgroups. RESULTS: A total of 2044 nutrition days in 178 patients were analyzed. The median estimated needs were 24 (interquartile range: 22.3-28.3) kcal/kg/day and 2.25 (interquartile range: 2.25-2.77) g/kg/day of protein using IBW in patients with obesity and actual weight in patients without obesity. Patients received 83% of energy and 63.3% of protein targets. Patients with obesity who received ≥2 g/kg IBW of protein had a significantly shorter ECMO duration (P = 0.037). Increased protein intake was independently associated with a reduced risk of death (odds ratio: 0.06; 95% confidence interval: 0.01-0.43). CONCLUSION: Higher protein intake was associated with reduced mortality. Optimal energy targets for patients receiving ECMO are currently unknown and warrant further study.
RESUMEN
BACKGROUND: The selective adenosine A2A receptor (A2AR) agonist regadenoson reduces inflammation due to lung ischemia-reperfusion injury (IRI). The objective of this study was to investigate molecular and cellular mechanisms by which regadenoson reduces IRI in lung transplant recipients. METHODS: Fourteen human lung transplant recipients were infused for 12 hours with regadenoson and 7 more served as untreated controls. Plasma levels of high mobility group box 1 and its soluble receptor for advanced glycation end-products (sRAGE) were measured by Luminex. Matrix metalloproteinase (MMP) 2 and 9 were measured by gelatin zymography. Tissue inhibitor of metalloproteinase 1 was measured by mass spectroscopy. A2AR expression on leukocytes was analyzed by flow cytometry. MMP-9-mediated cleavage of RAGE was evaluated using cultured macrophages in vitro. RESULTS: Regadenoson treatment during lung transplantation significantly reduced levels of MMP-9 (P < .05), but not MMP-2, and elevated levels of tissue inhibitor of metalloproteinase 1 (P < .05), an endogenous selective inhibitor of MMP-9. Regadenoson infusion significantly reduced plasma levels of sRAGE (P < .05) during lung reperfusion compared with control subjects. A2AR expression was highest on invariant natural killer T cells and higher on monocytes than other circulating immune cells (P < .05). The shedding of RAGE from cultured monocytes/macrophages was increased by MMP-9 stimulation and reduced by an MMP inhibitor or by A2AR agonists, regadenoson or ATL146e. CONCLUSIONS: In vivo and in vitro studies suggest that A2AR activation reduces sRAGE in part by inhibiting MMP-9 production by monocytes/macrophages. These results suggest a novel molecular mechanism by which A2AR agonists reduce primary graft dysfunction.
Asunto(s)
Productos Finales de Glicación Avanzada , Inhibidor Tisular de Metaloproteinasa-1 , Humanos , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Metaloproteinasa 9 de la Matriz , Reacción de Maillard , Pulmón/metabolismoRESUMEN
BACKGROUND: Adenosine inhibits the activation of most immune cells and platelets. Selective adenosine A2A receptor (A2AR) agonists such as regadenoson (RA) reduce inflammation in most tissues, including lungs injured by hypoxia, ischemia, transplantation, or sickle cell anemia, principally by suppressing the activation of invariant natural killer T (iNKT) cells. The anti-inflammatory effects of RA are magnified in injured tissues due to induction in immune cells of A2ARs and ecto-enzymes CD39 and CD73 that convert ATP to adenosine in the extracellular space. Here we describe the results of a five patient study designed to evaluate RA safety and to seek evidence of reduced cytokine storm in hospitalized COVID-19 patients. METHODS AND FINDINGS: Five COVID-19 patients requiring supplemental oxygen but not intubation (WHO stages 4-5) were infused IV with a loading RA dose of 5 µg/kg/h for 0.5 h followed by a maintenance dose of 1.44 µg/kg/h for 6 hours, Vital signs and arterial oxygen saturation were recorded, and blood samples were collected before, during and after RA infusion for analysis of CRP, D-dimer, circulating iNKT cell activation state and plasma levels of 13 proinflammatory cytokines. RA was devoid of serious side effects, and within 24 hours from the start of infusion was associated with increased oxygen saturation (93.8 ± 0.58 vs 96.6 ± 1.08%, P<0.05), decreased D-dimer (754 ± 17 vs 518 ± 98 ng/ml, P<0.05), and a trend toward decreased CRP (3.80 ± 1.40 vs 1.98 ± 0.74 mg/dL, P = 0.075). Circulating iNKT cells, but not conventional T cells, were highly activated in COVID-19 patients (65% vs 5% CD69+). RA infusion for 30 minutes reduced iNKT cell activation by 50% (P<0.01). RA infusion for 30 minutes did not influence plasma cytokines, but infusion for 4.5 or 24 hours reduced levels of 11 of 13 proinflammatory cytokines. In separate mouse studies, subcutaneous RA infusion from Alzet minipumps at 1.44 µg/kg/h increased 10-day survival of SARS-CoV-2-infected K18-hACE2 mice from 10 to 40% (P<0.001). CONCLUSIONS: Infused RA is safe and produces rapid anti-inflammatory effects mediated by A2A adenosine receptors on iNKT cells and possibly in part by A2ARs on other immune cells and platelets. We speculate that iNKT cells are activated by release of injury-induced glycolipid antigens and/or alarmins such as IL-33 derived from virally infected type II epithelial cells which in turn activate iNKT cells and secondarily other immune cells. Adenosine released from hypoxic tissues, or RA infused as an anti-inflammatory agent decrease proinflammatory cytokines and may be useful for treating cytokine storm in patients with Covid-19 or other inflammatory lung diseases or trauma.